Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Evolution (5)
- Climate change (3)
- Morphology (3)
- Performance (3)
- Sexual selection (3)
-
- Biology (2)
- Biomechanics (2)
- Brain (2)
- Development (2)
- Exercise (2)
- Kinematics (2)
- Mammal (2)
- Manduca sexta (2)
- Menopause (2)
- Migration (2)
- Mollusc (2)
- Muscle (2)
- Parasitism (2)
- Physiology (2)
- Plasticity (2)
- Programmed Cell Death (2)
- AAA+ (1)
- Abundance (1)
- Acheron (1)
- Acidobacteria (1)
- Acoustic landmarks (1)
- Adaptive radiation (1)
- Adaptors (1)
- African cichlid (1)
- African cichlids (1)
- Publication Year
Articles 31 - 60 of 80
Full-Text Articles in Life Sciences
Visual Attention In Jumping Spiders, Margaret Bruce
Visual Attention In Jumping Spiders, Margaret Bruce
Masters Theses
The different ways that animals extract and analyze visual information from their environment is of interest to sensory ecologists. Jumping spiders, well-known for visually guided mating and hunting behavior, are an interesting model for the study of visual attention because they quickly and efficiently integrate information from eight eyes with a small brain. Stimuli in front of the spider are examined by two functionally and morphologically distinct pairs of forward-facing eyes. The principal eyes discern fine details and have small retinas and thus a small visual field. However, their position at the back of moveable tubes within the cephalothorax expands …
Cardiovascular Disease Risk And Menopause: Effects Of Cardiorespiratory Fitness, Exercise, And Follicle Stimulating Hormone, Corinna Serviente
Cardiovascular Disease Risk And Menopause: Effects Of Cardiorespiratory Fitness, Exercise, And Follicle Stimulating Hormone, Corinna Serviente
Doctoral Dissertations
Menopause is associated with adverse changes in cardiovascular disease risk factors. A reduction in estrogens is most commonly associated with changing cardiovascular disease risk; however, recent observations suggest that the increase in follicle stimulating hormone that accompanies menopause may also influence risk, potentially through its influence on lipid levels. The changes in cardiovascular disease risk factors may adversely affect endothelial cell function, a pre-clinical marker for cardiovascular disease. Whether cardiorespiratory fitness is protective of endothelial health in this population, thereby mitigating the changes in risk that accompany menopause, is unclear. This dissertation evaluated differences in endothelial health and endothelial responses …
An Integrative Approach To Understanding Morphological Novelties: Anatomy, Development, Genetics, And Evolution Of An Extreme Craniofacial Trait In East African Cichlids, Moira R. Conith
Doctoral Dissertations
Phenotypic novelties are an important but poorly understood category of morphological diversity that are often associated with elevated rates of diversification and/or ecological success. The aim of this dissertation is to explore a phenotypic novelty at many levels to contribute to our understanding of how these unique traits can arise (e.g., genetically, developmentally, and evolutionarily) as well as their ecological consequences (e.g., trait function). The extreme snout of the Lake Malawi cichlid fish Labeotropheus is used as a case study. The first chapter establishes the Labeotropheus snout as a model of phenotypic novelty by characterizing the gross morphology, genetic architecture, …
Plants, Parasites, And Pollinators: The Effects Of Medicinal Pollens On A Common Gut Parasite In Bumble Bees, George Locascio
Plants, Parasites, And Pollinators: The Effects Of Medicinal Pollens On A Common Gut Parasite In Bumble Bees, George Locascio
Masters Theses
Declines in several pollinator species are due to a variety of factors, including pathogens. Incorporating pollinator-friendly plant species into wild and agricultural habitats could reduce the stress of pathogens if food sources act medicinally against pathogens. Previous research demonstrated one domesticated sunflower cultivar (Helianthus annuus) can dramatically reduce a gut pathogen (Crithidia bombi) of the common eastern bumble bee, Bombus impatiens. To ascertain the breadth of this medicinal trait, we tested whether pollen from several H. annuus cultivars and four relatives could also reduce C. bombi infections in B. impatiens. We also investigated whether …
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu
Doctoral Dissertations
During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …
Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres
Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres
Doctoral Dissertations
MicroRNA-155 (miR-155) is an important pro-inflammatory molecule that controls immune responses in both physiological and pathological settings. Although miR-155 is well studied, little is known about its transcriptional regulation in T cells. We sought to further understand the mechanisms by which miR-155 transcription is induced following T cell activation. We found that miR-155 transcription is dependent on the activity of the Notch and NFkB signaling pathways. It was determined that the canonical Notch signaling pathway was involved in this regulation and that it was dependent upon the activation of NFkB. Additional work confirmed that both NFkB and Notch1 directly bind …
Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu
Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu
Masters Theses
Fusion of cancer cells has been observed in tumors for more than a century and is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have developed a patterned gel system that can isolate cell fusion events and we demonstrate that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive …
Transposable Elements In Fusarium Oxysporum & Growth Inhibition Of Fusarium Oxysporum Using Pepper Extracts, Taylor Aguiar
Transposable Elements In Fusarium Oxysporum & Growth Inhibition Of Fusarium Oxysporum Using Pepper Extracts, Taylor Aguiar
Masters Theses
The following contains two projects focused on the fungal pathogen, Fusarium oxysporum. The first project was purely computational in the examination of transposable elements (TEs), which are mobile sequences with the ability to multiply and move in their host genome. In F. oxysporum, TEs such as miniature impala elements are associated with the secreted in xylem gene that are related to its virulence over its host. The F. oxysporum species complex can be utilized as a model system for the examination of TE content and TE expression during the infection cycle. To find whether TEs play a role …
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young
Doctoral Dissertations
Background: Nectar and pollen are rich in phytochemicals, some of which can reduce disease in pollinators, including agriculturally important honey and bumble bees. Floral phytochemicals could influence the ecological and evolutionary relationships between plants, their pollinators, and parasites that cause pollinator disease. Antiparasitic effects of phytochemicals could be exploited to ameliorate pollinator disease and decline, and thereby sustain pollinator-dependent agricultural production. However, prior studies showed variable effects of phytochemicals on infection in live bees, where differences in bee genotype, abiotic conditions, and parasite strain could influence results. Approach: I used cell cultures of the intestinal trypanosome parasite of bumble bees, …
Characterization Of Calcium Homeostasis Parameters In Trpv3 And Cav3.2 Double Null Mice, Aujan Mehregan
Characterization Of Calcium Homeostasis Parameters In Trpv3 And Cav3.2 Double Null Mice, Aujan Mehregan
Masters Theses
In mammals, calcium influx is required for oocyte maturation and egg activation, as it supports the persistent calcium oscillations induced by fertilization. These oscillations are required for the initiation of embryo development. The molecular identities of the plasma membrane calcium-permeant channels that underlie calcium influx are not established. Among these channels, Transient Receptor Potential Vanilloid, member 3 (TRPV3) allows divalent cations, namely strontium (Sr2+) and calcium (Ca2+) with high permeability, into cells, and its expression pattern seems to predict an essential role in the initiation of development. Another channel that was identified to be expressed in …
Uncovering Tasselsheath3. A Genomic And Phenotypic Analysis Of A Maize Floral Mutant., Thompson Zhang
Uncovering Tasselsheath3. A Genomic And Phenotypic Analysis Of A Maize Floral Mutant., Thompson Zhang
Masters Theses
In the modern era, maize has become the most successful crop grown in the United States. According to the USDA over 90 million acres of land are planted to corn and 96.2% of the U.S feed grain production is made up of the cereal. Part of the success of maize is due to its floral architecture, and its pollination technique in which the flower opens, exposing stamens containing pollen into the air. A unique organ called the lodicule functions as a release mechanism, forcing the flower to open. Lodicules from grasses and eudicot petals are homologous, yet there is little …
The Effect Of Pericyte Cell Therapy On Postischemic Neovascularization In Wild Type And Type 2 Diabetic Mice, Katherine E. Hayes
The Effect Of Pericyte Cell Therapy On Postischemic Neovascularization In Wild Type And Type 2 Diabetic Mice, Katherine E. Hayes
Doctoral Dissertations
Peripheral artery disease is an atherosclerotic disease that causes limb ischemia and has few effective treatments. Stem cell therapy is a promising treatment option, but concomitant diabetes may limit its effectiveness. The purpose of this study was to evaluate the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization following the induction of limb ischemia in wild type and type 2 diabetic (T2DM) mice. The hypothesis was that diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization and differentiate in vivo. Pericytes were isolated via fluorescence activated cell sorting for CD45-CD34-CD146 …
The Effects Of Anthropogenic Stress On Nitrogen-Cycling Microbial Communities In Temperate And Tropical Soils, George S. Hamaoui Jr.
The Effects Of Anthropogenic Stress On Nitrogen-Cycling Microbial Communities In Temperate And Tropical Soils, George S. Hamaoui Jr.
Doctoral Dissertations
In this dissertation several research studies are discussed that characterize the effects of anthropogenic, or human-induced, stress on both ammonia-oxidizing and total bacterial soil microbial communities. The disturbances of land-use change in tropical, South American rainforests and artificial warming and nitrogen (N) fertilization in temperate, North American forests were investigated as these disturbances represent past and current disturbances caused by human landscape alteration and climate change. Initially, the response of soil ammonia-oxidizing microbial communities to land-use change from primary rainforest to pasture and, finally, back to secondary forest was determined. Next, these analyses of land-use change effects were expanded to …
Potential Enhancement Of Dietary Isothiocyanates Combination On Biological Activities, Kanyasiri Rakariyatham
Potential Enhancement Of Dietary Isothiocyanates Combination On Biological Activities, Kanyasiri Rakariyatham
Doctoral Dissertations
Isothiocyanates (ITCs) such as allyl isothiocyanate (AIT) and sulforaphane (SFN) are well-known bioactives with wide range of beneficial properties, which may be consumed simultaneously through diets containing cruciferous vegetables. However, biological activities of ITCs in combinations had not been well defined. The present study evaluated the potential efficacy of AIT, SFN and their combinations on three important biological properties: anticancer, anti-inflammation and antioxidant. Our results showed that the combination between AIT and SFN led to a stronger growth inhibition on A549 non-small cell lung cancer cells than treatments with the individual compounds. The enhanced effect was proved to be synergistic …
The Role Of Phenotypic Integration In Mammalian Tooth Function And Jaw Morphological Diversity, Andrew Conith
The Role Of Phenotypic Integration In Mammalian Tooth Function And Jaw Morphological Diversity, Andrew Conith
Doctoral Dissertations
Here I investigate how two major components of the mammalian feeding system, teeth and jaws, are influenced by functional, environment, and developmental factors. First, I build physical models of the molars from two early mammals, Morganucodon and Kuehneotherium, and compare their ability to process a proxy food item. Early mammals were under strong selection to reduce metabolic costs, so any savings in energy during feeding would be advantageous. I tested the ability of both mammals to process a hard and soft food item with material properties similar to that of the insects they would have likely consumed. Morganucodon was …
Burrowing And Walking Mechanisms Of North American Moles, Yi-Fen Lin
Burrowing And Walking Mechanisms Of North American Moles, Yi-Fen Lin
Doctoral Dissertations
Moles (Family Talpidae) are a classic example of extreme specialization, in their case highly derived forelimb morphologies associated with burrowing. Despite many observations of mole burrows and behaviors gathered in the field, we know very little about how and how well moles use their forelimbs to dig tunnels and to walk within the built tunnels to collect and transport food. The first chapter investigates the effect of soil compactness on two sympatric mole species under controlled laboratory conditions. My results demonstrate that increasing soil compactness impedes tunneling performance as evidenced by reduced burrowing speed, increased soil transport, shorter tunnels, shorter …
Factors Influencing Impact Of Biological Control Agents Of The Emerald Ash Borer, Theresa Murphy
Factors Influencing Impact Of Biological Control Agents Of The Emerald Ash Borer, Theresa Murphy
Masters Theses
Agrilus planipennis, the emerald ash borer (EAB), is a destructive invasive forest pest decimating North American ash trees. Population-wide management of EAB focuses on biological control, with the introduction of four parasitic wasps; one egg parasitoid, Oobius agrili and three larval parasitoids- Spathius galinae, Spathius agrili and Tetrastichus planipennisi. This thesis examines some of the factors influencing the establishment of these larval biocontrol agents. Chapter 1 examines the relationship between woodpeckers and the parasitoids S. agrili and T. planipennisi. Both woodpeckers and these parasitoids attack the larval stage of EAB, which means their impacts overlap and …
An Adult Zebrafish Brain Atlas To Investigate Shh Mediated Cell-Cell Signaling In Neurogenic Zones, Alyssa P. Lutservitz
An Adult Zebrafish Brain Atlas To Investigate Shh Mediated Cell-Cell Signaling In Neurogenic Zones, Alyssa P. Lutservitz
Masters Theses
Adult neurogenesis occurs in proliferative zones of the brain that contain neural progenitor cell populations capable of differentiating into specific cell types. However, we remain limited in our understanding of the signals that regulate neural progenitor cell proliferation and differentiation in adults. Recently zebrafish (Danio rerio) have emerged as an excellent model for studying the molecular mechanisms behind adult neurogenesis, because sixteen proliferative zones remain active in the adult brains. Thousands of fluorescent transgenic reporter lines have been generated in zebrafish that reveal gene expression patterns of cell-cell signaling systems, some of which may regulate neurogenesis in these …
The Consequences Of Speed: Studies Of Cavitation During The Mantis Shrimp Strike And The Control Of Rapid Deceleration During Toad Landing, Suzanne M. Cox
The Consequences Of Speed: Studies Of Cavitation During The Mantis Shrimp Strike And The Control Of Rapid Deceleration During Toad Landing, Suzanne M. Cox
Doctoral Dissertations
There are consequences of moving quickly in this world. Here we investigate how two very different species, mantis shrimp (Odontodactylus scyllarus) and cane toads (Bufo marinus), negotiate forces that result from moving rapidly in different environments. To study the mechanical principles and fluid dynamics of ultrafast power-amplified systems, we built Ninjabot, a physical model of the extremely fast mantis shrimp. While mantis shrimp produce damaging cavitation upon impact with their prey, they do not cavitate during the forward portion of their strike despite extreme speeds. In order to study cavitation onset in non-linear flows common during …
The Role Of Micrornas In Regulating The Translatability And Stability Of Target Messenger Rnas During The Atrophy And Programmed Cell Death Of The Intersegmental Muscles Of The Tobacco Hawkmoth Manduca Sexta., Elizabeth Chan
Masters Theses
A variety of diseases lead to the atrophy and/or death of skeletal muscle. To better understand the molecular mechanisms that mediate these processes, I have taken advantage of the intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta, which undergo sequential programs of atrophy and programmed cell death at the end of metamorphosis. ISM death is mediated by changes in gene expression and numerous cell-death associated transcripts have been identified. MicroRNAs (miRs) are small (~22 nucleotide) non-coding RNAs that bind to sequences in messenger RNAs (mRNAs) and either cause translational arrest or mRNA degradation. To test the hypothesis that …
Spider Brain Morphology & Behavior, Skye M. Long
Spider Brain Morphology & Behavior, Skye M. Long
Doctoral Dissertations
Spiders are ideal model animals for experimental and comparative studies of behavior, learning and perception. They display many complex behaviors, such as the multimodal mating dances of lycosid spiders, the stealthy hunting strategies of the jumping spider Portia sp., to the labile sociality of theridiids. Spiders also demonstrate a wide range of cognitive capabilities. Spiders perceive their environment using multiple sensory modalities including: chemosensory organs; lyriform and slit-sense organs and specialized hairs that detect vibration and air movement; and up to eight eyes that vary in function, some able to detect polarization and a broad spectrum of light, including …
Chemically Mediated Interactions Between Hosts, Parasitic Plants And Insect Herbivores, Muvari C. Tjiurutue
Chemically Mediated Interactions Between Hosts, Parasitic Plants And Insect Herbivores, Muvari C. Tjiurutue
Doctoral Dissertations
Species interactions, by changing phenotypic traits, can alter the outcome of subsequent interactions. Plant-mediated responses to herbivores have been extensively studied, but little is known about plant-mediated responses involving parasitic plants within a broader community context that also includes herbivores. Because parasitic plants are important components of many ecosystems and can shape community structure, it is important to understand how host-mediated interactions influence parasite preference and success. The goal of this thesis is to examine interactions between hosts, parasitic plants and herbivores mediated by chemical traits. We first examined the effects of dodder (Cuscuta sp.) parasitism on induced defenses …
Curcumin And Its Oxidative Degradation Products: Their Comparative Effects On Inflammation, Julia Zhu
Curcumin And Its Oxidative Degradation Products: Their Comparative Effects On Inflammation, Julia Zhu
Masters Theses
The anti-inflammatory agent curcumin degrades rapidly, leading to speculations that curcumin’s reported effects stem from its degradation products. Curcumin can degrade via hydrolysis, and more recently it was discovered that curcumin can degrade via oxidation at physiological pH. Additionally, bicyclopentadione is the major degradation product from this oxidation reaction. Evidence from the literature suggests that curcumin degrades primarily through oxidation. However, the biology of the oxidation products is not well characterized, and there is debate on whether oxidation intermediates or curcumin itself is more biologically active. To further elucidate the biology of the oxidation products, their effects on inflammation were …
Evaluating A Novel Photochemical Tool For Labeling And Tracking Live, Endogenous Calcium-Permeable Ampars, Rosamund Elizabeth Combs-Bachmann
Evaluating A Novel Photochemical Tool For Labeling And Tracking Live, Endogenous Calcium-Permeable Ampars, Rosamund Elizabeth Combs-Bachmann
Masters Theses
The purpose of this research is to advance development of a photochemical tool designed to probe the role of ionotropic glutamate receptor signaling in neurodegenerative processes, and to delve more deeply into the biological processes underlying the role of these receptors in signaling and memory formation. This ligand-targeted nanoprobe was designed and developed in our lab to label endogenous calcium-permeable AMPARs (CP-AMPARs) in live cells with minimal disruption to native receptor activity. Nanoprobe is designed to use naphthyl acetyl spermine (NASPM) as a photocleavable ligand to target and covalently label native CP-AMPARs with a non-perturbing, fluorescent marker that then allows …
Evolvability Of The Skull: A Study Of Genetic Basis And Integration In The Teleost Craniofacial Skeleton, Yinan Hu
Doctoral Dissertations
As the field of evolutionary biology pivots away from a gene-centric view of how adaptive evolution proceeds, renewed emphasis is placed on the origin of phenotypic variation. Understanding the developmental processes that underlie the production of novel traits, and how they might influence evolvability, is considered a primary goal in the on-going “extended evolutionary synthesis”. The following dissertation explores these questions in the context of adaptive radiations in fish, with a focus on morphological variation in the craniofacial skeleton. Specifically, the first chapter investigates the genetic and developmental basis of shape (co-)variation in the feeding apparatus of African cichlid fishes, …
Promoting Extracellular Matrix Crosslinking In Synthetic Hydrogels, Marcos M. Manganare
Promoting Extracellular Matrix Crosslinking In Synthetic Hydrogels, Marcos M. Manganare
Masters Theses
The extracellular matrix (ECM) provides mechanical and biochemical support to tissues and cells. It is crucial for cell attachment, differentiation, and migration, as well as for ailment-associated processes such as angiogenesis, metastases and cancer development. An approach to study these phenomena is through emulation of the ECM by synthetic gels constructed of natural polymers, such as collagen and fibronectin, or simple but tunable materials such as poly(ethylene glycol) (PEG) crosslinked with short peptide sequences susceptible to digestion by metalloproteases and cell-binding domains. Our lab uses PEG gels to study cell behavior in three dimensions (3D). Although this system fosters cell …
Estimation Problems In Complex Field Studies With Deep Interactions: Time-To-Event And Local Regression Models For Environmental Effects On Vital Rates, Krzysztof M. Sakrejda
Estimation Problems In Complex Field Studies With Deep Interactions: Time-To-Event And Local Regression Models For Environmental Effects On Vital Rates, Krzysztof M. Sakrejda
Doctoral Dissertations
Field studies that measure vital rates in context over extended time periods are a cornerstone of our understanding of population processes. These studies inform us about the relationship between biological process and environmental noise in an irreplaceable way. These data sets bring ``big data'' and ``big model'' challenges, which limit the application of standard software (e.g., \textbf{BUGS}). The environmental sensitivity of vital rates is also expected to exhibit interactions and non-linearity, which typically result in difficult model selection questions in large data sets. Finally, long-term ecological data sets often contain complex temporal structure. In commonly applied discrete-time models complex temporal …
An Integrative, Cost-Benefit Analysis On Animal Perturbations: Autotomy And Life-History Related Weight Gain, Chi-Yun Kuo
An Integrative, Cost-Benefit Analysis On Animal Perturbations: Autotomy And Life-History Related Weight Gain, Chi-Yun Kuo
Doctoral Dissertations
The variation in behavioral traits and the adaptive significance behind such variation has been a classic question in behavioral ecology. Traits that enhance while simultaneously impose high fitness costs are particularly suitable for addressing this fundamental question, as their expressions are likely under strong selection. In this dissertation, I investigate the variation in a costly antipredator behavior and the underlying cost-benefit mechanisms. The trait of interest is the voluntary shedding of the tail, or tail autotomy, in lizards. Tail autotomy allows lizards to survive close-range encounters with predators but also has severe fitness consequences, including increased energetic demand for regeneration …
Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli
Engineering Novel Detection And Treatment Strategies For Bacterial Therapy Of Cancer, Jan T. Panteli
Doctoral Dissertations
Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due …
The Effects Of Ovarian Hormones And Exercise On Gene Markers Of Cardiac Dysfunction, Anisha S. Patel
The Effects Of Ovarian Hormones And Exercise On Gene Markers Of Cardiac Dysfunction, Anisha S. Patel
Masters Theses
Heart disease is the leading cause of death in women in the United States. Premenopausal women appear to have better cardiac function and lower risk of heart disease compared to male postmenopausal female counterparts. Ovarian hormone loss influences blood pressure homeostasis and causes systemic inflammation, which may result in chronic stress on the heart. Two key physiological changes in cardiac dysfunction are reemergence of the fetal gene pattern and myocardial remodeling. Physical activity has been linked to improved cardiac function. The purpose of this study was to investigate the effects of ovariectomy on early markers of cardiac dysfunction and fibrosis …