Miracle-dz/UniFAR-FTUs huggingface dataset:
The molecular pathology of Paget's disease of the vulva and the breast

Paget's disease of the vulva and breast are rare diseases. Unlike Paget's disease of the breast, where the consensus is that the great majority of cases are associated with an in-situ or invasive ductal carcinoma, only approximately 10-30% of cases of Paget's disease of the vulva have an invasive adenocarcinoma present. It is believed that the Paget cells in Paget's disease of the breast are derived from the underlying in-situ or invasive breast carcinoma, and these cells migrate up through the ducts onto the nipple epidermis. The histogenesis underlying vulval Paget's disease is unclear. Paget's disease of the vulva may become secondarily invasive even in the absence of an underlying malignancy. The aim of the study was to identify abnormalities present in Paget's diseases of the vulva and the breast and to investigate whether there are any differences in molecular markers in the Paget cells of those cases with invasive disease compared to those cases without invasive disease. Such an analysis may identify some of the molecular pathways underlying both vulval and breast Paget's disease, as well as generating potential markers for clinical prognosis. Archival paraffin wax-embedded sections of Paget's disease of the vulva or breast were used. Immunohistochemical analysis was performed to analyse markers involved in the cell cycle (p53, pRb, cyclin Dl, Ki67), in angiogenesis (e.g. VEGF, PD-ECGF/TP, MVD) and cell adhesion molecules (e.g. plakoglobin, E-cadherin, (3-catenin). Sections that were immunopositive for the tumour marker p53 were microdissected, the DNA extracted, amplified and sequenced. In situ hybridisation was also used to determine the presence of mRNA of the adhesion molecules in the tissue sections. A national register for Paget's disease of the vulva was established requesting that clinicians who have patients with Paget' s disease of the vulva should enrol them. Results suggest E-cadherin, plakoglobin and pRb and p53 may have a role to play in the pathogenesis of Paget's disease of the vulva and pRb, plakoglobin, VEGF and PD-ECGF/TP in Paget's disease of the breast. Wide local excison was the preferred treatment option for patients registered in the PDV database. The information from the Paget's register and the results obtained from the thesis may increase the understanding of Paget's disease of the vulva and breast.
Shallow genetic divergence and distinct phenotypic differences between two Andean hummingbirds: Speciation with gene flow?

ABSTRACT Ecological speciation can proceed despite genetic interchange when selection counteracts the homogenizing effects of migration. We tested predictions of this divergence-with-gene-flow model in Coeligena helianthea and C. bonapartei, 2 parapatric Andean hummingbirds with marked plumage divergence. We sequenced putatively neutral markers (mitochondrial DNA [mtDNA] and nuclear ultraconserved elements [UCEs]) to examine genetic structure and gene flow, and a candidate gene (MC1R) to assess its role underlying divergence in coloration. We also tested the prediction of Gloger's rule that darker forms occur in more humid environments, and examined morphological variation to assess adaptive mechanisms potentially promoting divergence. Genetic differentiation between species was low in both ND2 and UCEs. Coalescent estimates of migration were consistent with divergence with gene flow, but we cannot reject incomplete lineage sorting reflecting recent speciation as an explanation for patterns of genetic variation. MC1R variation was unrelated to phenotypic differences. Species did not differ in macroclimatic niches but were distinct in morphology. Although we reject adaptation to variation in macroclimatic conditions as a cause of divergence, speciation may have occurred in the face of gene flow driven by other ecological pressures or by sexual selection. Marked phenotypic divergence with no neutral genetic differentiation is remarkable for Neotropical birds, and makes C. helianthea and C. bonapartei an appropriate system in which to search for the genetic basis of species differences employing genomics.
Invertebrate prey contributions to juvenile Coho Salmon diet from riparian habitats along three Alaska streams: Implications for environmental change

Abstract Stream fish rely on a mix of terrestrial and aquatic prey sources. While the importance of terrestrial invertebrates as a food source for stream fish is well documented, the role of aquatic insects that emerge from the stream as winged adult insects (aquatic winged adults) and return to the stream as prey is less understood. In this study we determined the proportion of total diet for stream-rearing juvenile Coho Salmon (Oncorhynchus kisutch) that is derived from terrestrial and aquatic winged adult invertebrates which enter the stream from riparian habitats and consider how those cross-ecosystem prey contributions vary based on riparian habitat type. Study reaches were identified in three streams within the Kenai River watershed of Alaska that were representative of habitats found throughout the region and riparian vegetation was classified into grass/sedge, shrub and tree types using LiDAR. Juvenile Coho Salmon stomach contents were sampled seasonally in study reaches over a two-year period and ingested invertebrates were identified by taxa, life stage and origin. Our results showed that aquatic winged adult prey contributions to juvenile salmon diet were significantly lower in the grass/sedge study reach, and cross-ecosystem invertebrate prey represented a significantly higher proportion of juvenile salmon diet in the tree study reach. Invertebrate prey in the grass/sedge reach were composed primarily of the larval life stage of aquatic winged adults. These results suggest that change in riparian vegetation from tree/shrub to grass/sedge along Kenai streams as projected by regional climate change models, or that results from anthropogenic modification, will likely lead to lower availability of cross-ecosystem prey for stream fish. Management of riparian buffers along streams to preserve or increase occurrence of trees and shrubs is likely to help mitigate impacts of those possible changes.
Parkinson Disease in Twins

intheoriginofParkinsondisease(PD) has been debated for morethanacentury.Intheearly1980s,interest in an environmental cause of PDwasspurredbytheidentificationofbiologi-caleffectsoftheneurotoxicant1-methyl,4-phenyl,1,2,3,6-tetrahydropyridine(MPTP). Thisrelativelysimplepyridinemoietyin-ducesmostifnotallofthesignsandsymp-tomsofPDinhumans
A critical appraisal of appendage disparity and homology in fishes

Homology is a fundamental concept in biological sciences (Hall, 1994a). Homologous characters are quintessential for phylogenetic analyses, while also providing traits that can be used to identify taxa for taxonomists, and traits that can be compared among clades for evolutionary biologists. However, there is a lack of consensus among biologists as to the criteria that should be used to establish homol‐ ogy (e.g., similarity through topographical correspondence and/or ontogenetic transformation, congruence or anatomical singularity, shared developmental processes, common evolutionary origins; Hall, 1994b; Patterson, 1982, 1988). All this considered, identifying homologies of morphological traits across large phylogenetic scales is not always straightforward, as many structures are likely to have accrued changes in morphology and function over evolutionary time. Fish appendages represent one such case where homologies have historically been difficult to interpret. Among the factors that com‐ plicate inferring fin homologies are that fishes are both extremely Received: 9 February 2019 | Revised: 19 July 2019 | Accepted: 29 July 2019 DOI: 10.1111/faf.12402
Olfactory landmarks and path integration converge to form a cognitive spatial map

The convergence of internal path integration with sensory information from external landmarks generates a cognitive spatial map in the hippocampus. We have recorded the activity of cells in CA1 during a virtual navigation task to examine how mice represent, recognize and employ sparse olfactory landmarks to estimate their location. We observe that the presence of odor landmarks at multiple locations in a virtual environment greatly enriches the place cell representation and dramatically improves navigation. Presentation of the same odor at different locations generates distinct place cell representations, indicating that path integration can disambiguate two identical cues on the basis of location. The enhanced place cell representation at one cue location led to the formation of place cells at locations beyond that cue and, ultimately recognition of a second odor cue as a distinct landmark. This suggests an iterative mechanism for extending place cell representations into unknown territory. These results reveal how odor cues can serve as landmarks to guide navigation and suggest a model to explain how the convergence of landmarks and path integration participates in an iterative process that generates a cognitive spatial map.
Sex-biased dispersal patterns of a social passerine: complementary approaches and evidence for a role of spatial scale

Animal dispersal patterns have important implications for many biological processes, but the measurement of dispersal is challenging and often requires the use of complementary approaches. In this study, we investigated the local-scale sex-biased dispersal pattern in a social bird, the black-throated tit (Aegithalos concinnus), in central China. Spatial genetic autocorrelation analyses suggested that significant fine-scale genetic structure existed in males but not in females. Mark–recapture analyses of ringed individuals also showed that female offspring were more dispersive than male offspring, supporting genetic evidence of local female-biased dispersal. These results were contrary to a previous finding of male-biased long-distance dispersal in this species that was based on analyses of gene flow across the species range in China. This implies that the species might potentially have a scale-dependent dispersal strategy, with females frequently dispersing further than males at the local level, but with a proportion of males occasionally dispersing over long distances and contributing more to gene flow at a larger geographical scale. Long-distance dispersal by male black-throated tits might be induced by competition for resources or by unfavourable environmental conditions, warranting further investigation, but our findings increase the evidence that geographical scale is an important factor to be considered when investigating animal dispersal patterns.
Influence of sand grain size and nest microenvironment on incubation success, hatchling morphology and locomotion performance of green turtles (Chelonia mydas) at the Chagar Hutang Turtle Sanctuary, Redang Island, Malaysia

Abstract. The nest microenvironment affects hatching and emergence success, sex ratios, morphology, and locomotion performance of hatchling sea turtles. Sand grain size is hypothesised to influence the nest microenvironment, but the influence of sand grain size on incubation of sea turtle eggs has rarely been experimentally tested. At the Chagar Hutang Turtle Sanctuary, Redang Island, Malaysia, green turtle (Chelonia mydas) nests were relocated to sands with different sand grain sizes on a natural beach to assess whether grain size affects nest temperature, oxygen partial pressure inside the nest, incubation success, hatchling morphology and hatchling locomotion performance. Green turtle nests in coarse sand were cooler; however, hatching success, nest emergence success, oxygen partial pressure, incubation length and hatchling size were not influenced by sand particle size. Nests in medium-grained sands were warmest, and hatchlings from these nests were better self-righters but poorer crawlers and swimmers. Hatchling self-righting ability was not correlated with crawling speed or swimming speed, but crawling speed was correlated with swimming speed, with hatchlings typically swimming 1.5–2 times faster than they crawled. Hence, we found that sand particle size had minimal influence on the nest microenvironment and hatchling outcomes.
Genetic structure and diversity of the blueface darter Etheostoma cyanoprosopum, a microendemic freshwater fish in the southeastern USA

Darters represent one of the most diverse groups of freshwater fishes in North America, but approximately 33% of the 215 recognized species are considered imperiled on the IUCN Red List. Discovery and description of new darter species continue at a relatively rapid pace, with many exhibiting microendemic geographic distributions and little baseline data for conservation decisions. The blueface darter Etheostoma cyanoprosopum is a newly described species that occupies <20 km of stream reaches in the Bear Creek system of the Tennessee River drainage and the Hubbard Creek system of the Black Warrior River drainage in the Mobile Basin (Alabama, USA). In addition to restricted distribution, the species is threatened by habitat degradation and several natural and man-made barriers that putatively fragment connectivity among populations. This study used microsatellite DNA and mitochondrial DNA (mtDNA) data with comparisons to the relatively broadly distributed sister species (bandfin darter E. zonistium) to evaluate multiple objectives regarding genetic connectivity and diversity among blueface darter populations. Ana lysis of mtDNA data indicated a lack of historical structuring across the Tennessee−Black Warrior River drainage divide and within the Bear Creek system. However, microsatellite-based Bayesian cluster analyses and F-statistics suggested contemporary isolation across the drainage divide and evidence for reservoir-induced fragmentation within the Bear Creek system. Compared to the sister bandfin darter, blueface darter populations exhibited reduced levels of genetic diversity, rendering them more susceptible to local extirpation and reduced fitness. Continued monitoring and quantitative ecological studies are recommended to understand population-specific measures of occurrence and abundance.
A novel xenograft model of human HCC in immunocompetent mouse

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human liver cancer is of important practical significance. Taking advantage of the novel microcarrier-6, human HCC cells was injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh liver cancer tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry. The success rate was 60% (6/10) in the establishment of liver cancer PDX mouse model, and the total tumor formation rate of the tumor-forming model is 80-100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced. Through the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC.
Fluoxetine improves behavioural deficits induced by chronic alcohol addiction by alleviating RNA editing of 5-HT2C receptors in astrocytes

The alcoholism and major depressive disorder are common comorbidity, with alcohol-induced depressive symptoms being eased by selective serotonin re-uptake inhibitors (SSRIs), although the mechanisms underlying pathology and therapy are poorly understood. Chronic alcohol consumption affects the activity of serotonin 2C receptors (5-HT2CR) by regulating adenosine deaminases acting on RNA (ADARs) in neurones. Astrogliopathic changes contribute to alcohol addiction, while decreased release of ATP from astrocytes can trigger depressive-like behaviours in mice. In this study, we discovered that chronic alcohol addiction increased editing of RNA of 5-HT2CR via up-regulating the expression of ADAR2, consequnetly reducing the release of ATP from astrocytes induced by 5-HT2CR agonist, MK212. At the same time SSRI antidepressant fluoxetine decreased the expression of ADAR2 through the transactivation of EGFR/PI3K/AKT/cFos signalling pathway. Reduction in ADAR2 activity eliminated the RNA editing of 5-HT2CR in vivo and increased release of astroglial ATP which was suppressed by chronic alcohol consumption. Meanwhile, fluoxetine improved the behavioural and motor symptoms induced by alcohol addiction and decreased the alcohol intake. Our study suggests that the astrocytic 5-HT2CR contribute to alcohol addiction; fluoxetine thus can be used to alleviate depression, treat alcohol addiction and improve motor coordination.
The gammaherpesvirus 68 viral cyclin facilitates reactivation by promoting latent gene expression

Gammaherpesviruses establish life-long infections within their host and have been shown to be the causative agents of devastating malignancies. Chronic infection within the host is mediated through cycles of transcriptionally quiescent stages of latency with periods of reactivation into more active lytic and productive infection. The mechanisms that regulate reactivation from latency remain poorly understood. Previously, we defined a critical role for the viral cyclin in promoting reactivation from latency. Disruption of the viral cyclin had no impact on the frequency of cells containing viral genome during latency, yet it remains unclear whether the viral cyclin influences latently infected cells in a qualitative manner. To define the impact of the viral cyclin on latent gene expression, we utilized a viral cyclin deficient variant expressing a LANA-beta-lactamase fusion protein (LANA::βla), to enumerate both the cellular distribution and frequency of latent gene expression. Disruption of the viral cyclin did not affect the cellular distribution of latently infected cells, but did result in a significant decrease in the frequency of cells that expressed LANA::βla across multiple tissues and in both immunocompetent and immunodeficient hosts. Strikingly, whereas the cyclin-deficient virus had a reactivation defect in bulk culture, sort purified cyclin-deficient LANA::βla expressing cells were fully capable of reactivation. These data emphasize that the γHV68 latent reservoir is comprised of at least two distinct stages of infection characterized by differential latent gene expression, and that a primary function of the viral cyclin is to promote latent gene expression within infected cells in vivo. AUTHOR SUMMARY Gammaherpesviruses are ubiquitous viruses with oncogenic potential that establish latency for the life of the host. These viruses can emerge from latency through reactivation, a process that is controlled by the immune system. Control of viral latency and reactivation is thought to be critical to prevent γHV-associated disease. This study focuses on a virally-encoded cyclin that is required for reactivation from latency. By characterizing how the viral cyclin influences latent infection in pure cell populations, we find that the viral cyclin has a vital role in promoting viral gene expression during latency. This work provides new insight into the function of a virally encoded cyclin in promoting reactivation from latency.
Resistance and Tolerance to Root Herbivory in Maize Were Mediated by Domestication, Spread, and Breeding

Plants may defend against herbivory and disease through various means. Plant defensive strategies against herbivores include resistance and tolerance, which may have metabolic costs that affect plant growth and reproduction. Thus, expression of these strategies may be mediated by a variety of factors, such as resource availability, herbivory pressure, and plant genetic variation, among others. Additionally, artificial selection by farmers and systematic breeding by scientists may mediate the expression of resistance and tolerance in crop plants. In this study, we tested whether maize defense against Western corn rootworm (WCR) was mediated by the crop’s domestication, spread, and modern breeding. We expected to find a trend of decreasing resistance to WCR with maize domestication, spread, and breeding, and a trend of increasing tolerance with decreasing resistance. To test our expectations, we compared resistance and tolerance among four Zea plants spanning those processes: Balsas teosinte, Mexican landrace maize, US landrace maize, and US inbred maize. We measured performance of WCR larvae as a proxy for plant resistance, and plant growth as affected by WCR feeding as a proxy for plant tolerance. Our results showed that domestication and spread decreased maize resistance to WCR, as expected, whereas breeding increased maize resistance to WCR, contrary to expected. Our results also showed that maize resistance and tolerance to WCR are negatively correlated, as expected. We discussed our findings in relation to ecological-evolutionary hypotheses seeking to explain defense strategy evolution in the contexts of plant resistance-productivity trade-offs, plant tolerance-resistance trade-offs, and varying resource availability vis-à-vis plant physiological stress and herbivory pressure. Finally, we suggested that defense strategy evolution in maize, from domestication to the present, is predicted by those ecological-evolutionary hypotheses.
Seed Predation by Owyhee Harvester Ants and the Potential of Seed Introductions in Recovery Efforts for Slickspot Peppergrass

vii LIST OF TABLES . xi LIST OF FIGURES . xii CHAPTER ONE: CONSEQUENCES OF OWYHEE HARVESTER ANT (POGONOMYRMEX SALINUS) FORAGING BEHAVIOR ON SEED RECRUITMENT IN SLICKSPOT PEPPERGRASS (LEPIDIUM PAPILLIFERUM) . 1 Abstract . 1.
Prognostic Value of Lymphovascular Invasion in Upper Urinary Tract Urothelial Carcinoma after Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

This study was performed to identify the prognostic impact of lymphovascular invasion (LVI) in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). A systematic search in PubMed, Embase, and the Cochrane Library was performed to identify relevant studies. The outcomes of interest, including progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were extracted, and the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used for effect size estimation. Subgroup, metaregression, and sensitivity analyses were performed to explore potential origins of heterogeneity. Publication bias was estimated by Egger's linear regression and funnel plot. Our meta-analysis included a total of 27 studies involving 17,453 patients. The pooled HRs were statistically significant for PFS (HR = 1.73, 95%CI = 1.41–2.11), CSS (HR = 1.87, 95%CI = 1.54–2.27), and OS (HR = 1.56, 95%CI = 1.29–1.87), with high heterogeneity (I2 = 77.8%, 70.3%, and 59.2%, respectively). Four studies explored the prognostic value of LVI in patients with advanced tumor stages (T3–T4). The fixed effects model (I2 = 33.9%) showed that the pooled HR was 1.64 (95%CI = 1.35–1.99) for CSS. Egger's plots showed no significant publication bias (PFS: P = 0.443, CSS: P = 0.096, and OS: P = 0.894). Our meta-analysis demonstrated that LVI is a poor prognostic factor for UTUC and is strongly associated with disease recurrence, cancer-specific mortality, and overall mortality.