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Articles 20101 - 20130 of 21283
Full-Text Articles in Entire DC Network
The Effects Of Inter-Age Class Competition On Habitat Use In A Territorial Lizard, David Michael Delaney
The Effects Of Inter-Age Class Competition On Habitat Use In A Territorial Lizard, David Michael Delaney
All ETDs from UAB
All organisms have specific habitat requirements that allow them to properly function in the environment. However, optimal habitats often differ across age classes, and accordingly, juveniles shift habitat choice as they age. Field observations of the brown anole lizard (Anolis sagrei) suggest that juveniles perch in open-canopy areas on low vegetation whereas adults reside in forest edges on higher vegetation. I hypothesized that this age-specific habitat variation is because adults force juveniles to less preferred habitat. To address these issues, I conducted a series of experiments to examine the role of inter-age class competition in driving variation in perch use …
Exploiting The Glioblastoma Tumor Microenvironment For Enhanced Oncolytic Herpes Simplex Virus Therapy, Tyrel Talbert Smith
Exploiting The Glioblastoma Tumor Microenvironment For Enhanced Oncolytic Herpes Simplex Virus Therapy, Tyrel Talbert Smith
All ETDs from UAB
Gliomas are the most common and fatal malignancy of the adult central nervous system. The need for new therapeutic options is clear, as standard of care therapies only extend median survival 12-14 months beyond diagnosis. Conditionally replication-competent oncolytic herpes simplex type-1 viruses (oHSV) have emerged as promising therapeutics for treating malignant gliomas. However, two factors that contribute to the dismal prognosis of malignant gliomas, immunosuppression and invasive growth, are also thought to limit virotherapeutic efficacy. We examined these factors in tumor microenvironments to explore novel strategies to treat malignant gliomas with oHSV for improved therapeutic response. In a Phase 1b …
Characterization Of The Gtpase Rac1 As An Electrophilic-Sensitive Protein In Vascular Cells, Stephanie Brook Wall
Characterization Of The Gtpase Rac1 As An Electrophilic-Sensitive Protein In Vascular Cells, Stephanie Brook Wall
All ETDs from UAB
The GTPase Rac1 is a protein which has been shown to be dysregulated in the context of a number of inflammatory diseases including atherosclerosis. Rac1 responds to extracellular signals and is involved in cellular cytoskeletal rearrangement, reactive oxygen species generation and cell cycle progression. When activated Rac1 interacts with effector proteins on the plasma membrane. This activation has recently been shown to be modulated by redox signaling via an active site cysteine. However, it is not known whether other redox signaling compounds can modulate Rac1 activity. An important redox signaling mediator is the electrophilic lipid, 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2). This lipid …
A Bio-Inspired Hybrid Nanosack For Pancreatic Islet Transplantation In The Omentum, Patrick Tj Hwang
A Bio-Inspired Hybrid Nanosack For Pancreatic Islet Transplantation In The Omentum, Patrick Tj Hwang
All ETDs from UAB
Pancreatic islet transplantation (PIT) has demonstrated consistent and sustained reversal of type 1 diabetes, generating optimism for its wider application as a potential cure for type 1 diabetes. However, the clinical efficacy is still lacking because of a substantial loss of islets during or shortly after transplant to the implantation site. The liver has been widely used as an implantation site for PIT, but it has serious risks for islet loss, such as massive islet destruction by instant blood-mediated inflammatory reaction, progressive attrition of islet cells due to exposure to the toxic environment. The omentum has gained significant attention as …
Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull
Mechanisms Of Heme Oxygenase-1-Mediated Protection Against Tissue Injury, Travis David Hull
All ETDs from UAB
Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in the catabolism of heme, which is released by necrotic cells in injured tissue. HO-1 expression is protective in cardiac and renal injury because it coordinates the degradation of pro-oxidant heme with the generation of equimolar quantities of iron (Fe2+) and the cytoprotective mole-cules carbon monoxide and biliverdin. While many studies have demonstrated that HO-1 expression is protective in numerous disease states, relatively few have examined the specific cellular compartment(s) through which HO-1 expression confers its protective effects. Our objective was to define the cellular compartments in which HO-1 expression is critical to …
Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson
Mechanisms Of Resistance To Oncolytic Herpes Simplex Viruses In Malignant Peripheral Nerve Sheath Tumors, Joshua Douglas Jackson
All ETDs from UAB
Malignant peripheral nerve sheath tumors (MPNSTs) are rare but highly aggressive cancer of the peripheral nervous tissue. Median patient survival is approximately two years following diagnosis due in part to the ineffective options for treatment. As an alternative therapeutic approach to conventional radio- and chemotherapy, oncolytic herpes simplex viruses type-1 (oHSVs) have been proposed to treat MPNSTs. These oHSVs have been shown safe in clinical trials with associated tumor regression. However, there is evidence that resistance to the therapy should be anticipated in a subset of patients. Therefore, the goal of this dissertation has been to identify the primary obstacles …
Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson
Zebrafish Wnt9b Patterns The First Pharyngeal Arch Into D-I-V Domains And Promotes Anterior-Medial Outgrowth, Henry Jackson
All ETDs from UAB
The secondary mouth and its associated face and jaws were an important evolutionary adaptation in the vertebrate lineage. The secondary mouth is formed from facial prominences including the fronto-nasal prominence and the 1st pharyngeal-arch derived maxillary and mandibular prominence. Cranial neural crest cells within these prominences give rise to the connective tissues of face and jaws, and strict spatio-temporal regulation of cranial neural crest cell fate patterning and subsequent prominence outgrowth is vital to normal facial development. Oral-facial clefting (OFC) is a common morbid human birth disorder characterized by disrupted oral and craniofacial morphogenesis. Our previous studies demonstrate that a …
Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar
Regulation Of Cks1 Protein Turnover In Cancer Cells, Vinayak Khattar
All ETDs from UAB
Cks1 is a crucial cell cycle regulator which plays pleiotropic roles in cancer cell growth and is highly expressed at both the protein, and mRNA levels, in cancer cells. In contrast, normal cells exhibit barely detectable levels of this protein, even though they express substantial Cks1 mRNA. One reason for high Cks1 protein in cancers appears to be its stabilization in these cells. Cks1 is known to be ubiquitinated and degraded by the proteasome. Coordinated ubiquitination dependent proteasomal degradation of cell cycle proteins is a major mechanism that regulates their activity. Therefore aberrant accumulation of Cks1, frequently observed in cancer, …
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
All ETDs from UAB
Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …
An Nphp-4 Enhancer Mutagenesis Screen For Modifiers Of Cilia Phenotypes Reveals Novel Mks Alleles, Uncovers, A Specific Genetic Interaction Between Osm-3 And Nphp-4, And A Novel Ciliary Calcium Channel., Dawn Landis
All ETDs from UAB
Nephronophthisis (NPHP) is a ciliopathy with diverse clinical features likely caused by genetic modifiers. To identify NPHP modifiers, a screen was conducted on nphp-4(tm925) mutant C. elegans to reveal mutations that exacerbate the NPHP ciliary defects. Ten loci were generated, five of which have now been identified. Three are mutations in ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. As in osm-3 null mutants, nphp-4(tm925);osm-3(yhw66) mutants lack distal segments, are dye-filing defective (Dyf), and have osmotic avoidance defects (OSM). The osm-3(yhw66) mutant alone …
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
14-3-3 Proteins Regulate Mutant Lrrk2 Kinase Activity And Neurite Shortening, Nicholas Lavalley
All ETDs from UAB
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson’s disease (PD), and LRRK2 is a risk factor for idiopathic PD. How LRRK2 function is regulated is not well understood. Recently, the highly-conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2. In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity. In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wildtype levels. Similarly, 14-3-3θ overexpression …
Changes In The Frontal Soft Tissue Of The Lower Face By Age And Sex, Maggie Law
Changes In The Frontal Soft Tissue Of The Lower Face By Age And Sex, Maggie Law
All ETDs from UAB
The purpose of this study is to determine age-related changes of the lower face by age and by gender. The secondary purpose of this study is to stress the importance of the clin-ical exam for orthodontic patients in the frontal view, the way most patients perceive themselves. Also, individualized treatment planning with age-appropriate incisor display is crucial for esthetic outcomes. Materials and Methods: Specific dimensions of the lower face were measured at patients initial clinical exam before starting orthodontic treatment. All patients were from Dr. David Sarver's private practice in Vestavia Hills, AL collected from 1/1/2002-11/4/2014. The following parameters were …
The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu
The Jak/Stat Pathway In Neuroinflammatory Diseases, Yudong Liu
All ETDs from UAB
Dysregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway is critically involved in the pathogenesis of multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE). Suppressor Of Cytokine Signaling (SOCS) proteins are the negative regulators of the JAK/STAT pathway. To determine the role of SOCS3 in myeloid cells in EAE, mice with conditional SOCS3 deletion in myeloid cells (LysMCre-SOCS3fl/fl) were created and tested. LysMCre-SOCS3fl/fl mice develop a severe, non-resolving atypical form of disease, characterized by lesions and extensive neutrophil and other inflammatory cell infiltrates in the cerebellum and brainstem, elevated STAT activation, elevated cytokine, chemokine and iNOS expression, and prominent …
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu
All ETDs from UAB
Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …
Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum
Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum
All ETDs from UAB
Schizophrenia is a mental illness affecting 1% of the population worldwide. Treatment options are limited for patients, due in part to the lack of understanding of the pathophysiological mechanisms of schizophrenia. In order to improve treatment, it is vital to gain a better understanding of the underlying pathology of the disorder. One region of particular interest is the nucleus accumbens (NAcc). Part of the ventral striatum, this region is thought to play a role in schizophrenia pathology for multiple reasons: afferent input of many brain regions implicated in schizophrenia is integrated here; the dopamine and glutamate systems, both known to …
They Pull Your Grown Up Card For This, Jamie Mcfaden
They Pull Your Grown Up Card For This, Jamie Mcfaden
All ETDs from UAB
THEY PULL YOUR GROWN-UP CARD FOR THIS JAMIE MCFADEN MASTER OF ARTS IN ENGLISH ABSTRACT They Pull Your Grown-Up Card for This is a collection of six nonfiction pieces. The majority of the pieces in the collection are personal essays with the exception of one written specifically as nonfictional prose and another that adheres to the memoir tradition. Major themes coursing through this body of work include notions of family, friendship, and self-awareness.
A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown
A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown
All ETDs from UAB
In the first step in light perception, rod and cone photoreceptors convert photon absorption into an electrical impulse that is transmitted through the visual pathway. While the biochemistry and the signaling physiology have largely been defined in dark-adapted, isolated mammalian rods, there are still unanswered questions regarding photoreceptor light adaptation processes that involve extracellular components. In particular, the proteins of the interphotoreceptor matrix have not been considered in the studies of rod signaling and adaptation. This thesis details a new form of light adaptation, now known as adaptive potentiation (AP), in which extracellular components act on rods to transiently increase …
Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows
Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows
All ETDs from UAB
Learning and memory rely on long-lasting, experience-dependent adaptations in synaptic and non-synaptic forms of neuronal plasticity. Previous evidence implicates transcriptional and epigenetic mechanisms, including DNA cytosine methylation, as critical regulators of site-specific, Hebbian alterations in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). However, whether DNA methylation modulates cell-wide, non-Hebbian homeostatic adaptations like synaptic scaling and intrinsic plasticity (IP) is unclear. Whereas synaptic scaling involves bidirectional changes in postsynaptic receptor density in response to chronic alterations in neuronal activity, IP involves the activity-dependent attunement of passive and/or active membrane properties that govern action potential (AP) firing. This …
The Impact Of Meal Timing On Cardiometabolic Syndrome Indicators In Shift Workers, Hylton Elisabeth Molzof
The Impact Of Meal Timing On Cardiometabolic Syndrome Indicators In Shift Workers, Hylton Elisabeth Molzof
All ETDs from UAB
Shift workers exhibit a greater risk for several cardiovascular and metabolic diseases including heart disease, obesity, hypertension, and type II diabetes (Boivin, Tremblay, & James, 2007; Chen, Lin, & Hsiao, 2010; Knutsson, Jonsson, Akerstedt, & Orth-Gomer, 1986; Kroenke et al., 2007). Shift workers have been reported to consume more pro-inflammatory diets than day workers (Wirth, Burch, Shivappa, Steck, et al., 2014) and to redistribute their food intake to the night during work (Lennernas, Hambraeus, & Akerstedt, 1995; Pasqua & Moreno, 2004). Numerous studies in animal models and humans have shown that eating during the sleep or inactive period is associated …
Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett
Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett
All ETDs from UAB
Type 1 Diabetes (T1D) is an autoimmune disease culminating in pancreatic β-cell destruction, inducing reactive oxygen species (ROS), pro-inflammatory cytokines, and islet-infiltrating leukocutes. Macrophages, one of the first islet-infiltrating cells in T1D, secrete ROS and pro-inflammatory cytokines, which lyse pancreatic β-cells and activate diabetogenic T cells to further propagate β-cell destruction, while autoreactive CD4 T cells recruit islet-infiltrating, pro-inflammatory, M1 macrophages, and enhance CD8 T cell cytotoxicity. We previously demonstrated the importance of NADPH oxidase (NOX)-derived ROS synthesis in T1D, as Non-obese diabetic (NOD) mice lacking NOX-derived superoxide (NOD.Ncf1m1J) exhibited a delay in spontaneous and adoptive transfer of T1D. In …
Comparison Of Three Fluoride Dentifrice Products In The Prevention Of White Spot Lesions In Orthodontic Treatment, Anna B. Palombini
Comparison Of Three Fluoride Dentifrice Products In The Prevention Of White Spot Lesions In Orthodontic Treatment, Anna B. Palombini
All ETDs from UAB
Introduction:. During the course of orthodontic treatment, enamel decalcification is a common problem. Demineralized enamel, the precursor to caries formation, can be attributed to fixed orthodontic appliances and prolonged exposure to bacterial plaque. Progression to clinically detectable white spot lesions may occur as early as one month following the placement of orthodontic appliances. Such problems have influenced clinicians to search for a solution. Because fluoride treatment immediately upon debonding is not advocated, clinicians have proposed fluoride treatment and fluoride-releasing materials at the commencement of the therapy. The two new anti-cavity toothpastes, ClinproTM 5000 with 1.1% Sodium Fluoride and ClinproTM Tooth …
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues
All ETDs from UAB
Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …
With Love, Flint, Sharanna Polk
With Love, Flint, Sharanna Polk
All ETDs from UAB
While With Love, Flint includes nine short stories that work together to tell the story of a slave woman’s descendants, each story is written so that it can stand separate from the entire piece. With Love, Flint begins in the year 1849 in Madison Mississippi, and travels through Memphis, New Orleans, Mobile and finally settles in Flint, Michigan, ending in 2013. The first five stories detail how each character eventually arrives in Flint, detailing some of America’s history along the way. The stories and characters are meant to reflect and offer exploration of Flint Michigan’s detriment. Through the characters, the …
Orthogonal Pulse Based Wideband Communication For High Speed Data Transfer In Sensor Applications, Kushal Prasad Pradhan
Orthogonal Pulse Based Wideband Communication For High Speed Data Transfer In Sensor Applications, Kushal Prasad Pradhan
All ETDs from UAB
There has been an ever increasing demand and need for high speed and reliable data transfer between a remote transmitter and a receiver station. We have proposed a novel scheme for Ultra Wide Band (UWB) communication technology, to enhance the data rate in single user scenario and to increase the number of sources for simultaneous data transmission in the multi-source scenario. We have proposed to exploit the orthogonal property of Modified Hermite Pulse (MHP) by transmitting the composite pulse (Pulse shape modulation, PSM) instead of transmitting a single orthogonal pulse. With the proposed scheme for data modulation with 4 different …
Cash, Conscience, Corpse: The Culture Of Death In The Victorian Novel, Harvey Ragland
Cash, Conscience, Corpse: The Culture Of Death In The Victorian Novel, Harvey Ragland
All ETDs from UAB
ABSTRACT This thesis discusses Victorian notions of respectability at death and burial as they are portrayed in Jane Eyre, David Copperfield, Middlemarch, and The Nether World. Because such notions are, by nature, fluid in that the death of an individual is spread across a canvas of public ritual, the novel provides a better way than newspaper accounts or diaries to bring together divergent and competing perspectives to form a more complete account of respectability's meaning for Victorians. Each of the four novels takes a different position on the idea of the respectable death and customs associated with it. From the …
Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi
Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi
All ETDs from UAB
The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert
All ETDs from UAB
Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …
Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue
All ETDs from UAB
A nonsense mutation introduces a premature terminations codon (PTC) into an open reading frame (ORF) upstream of a normal stop codon and results in truncated protein production. In frame PTCs account for ~11% of all mutations that cause human genetic diseases. To treat PTC-associated disorders, one approach is to use drugs that facilitate the insertion of amino acids carried by near-cognate aminoacyl-tRNAs at PTCs. Aminoglycosides were shown to suppress nonsense mutations and restore full-length protein production. This process is also termed as readthrough. However, their low efficiency and their potential to induce ototoxicity and nephrotoxicity limits their long-term application for …
Computational Studies On Alpha-Synuclein In Explicit Solvent: Implications In Parkinson’S Disease, Hongyi Yang
Computational Studies On Alpha-Synuclein In Explicit Solvent: Implications In Parkinson’S Disease, Hongyi Yang
All ETDs from UAB
α-Synuclein (αS) is a cytosolic protein expressed at high levels in the human brain and concentrated in presynaptic nerve terminals. Although the precise nature of αS in vivo remains unclear, the aggregation of αS, from its soluble, functional forms into highly organized amyloid fibrils, has been substantially implicated in the pathology of a number of neurodegenerative diseases collectively known as synucleinopathies. The long-term goal of this project is to understand the molecular mechanisms that initiate αS oligomerization in aqueous solution. A novel computational methodology involving protein modeling and atomistic molecular dynamics (MD) simulations is used in this work. The objective …
Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu
Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu
All ETDs from UAB
STAT3 signaling is a major intrinsic pathway for cancer inflammation owing to its frequent activation in malignant cells, and key role in regulating many genes crucial for inflammation in the tumor microenvironment. Persistently activated STAT3 increases tumor cell proliferation, survival, and invasion while suppressing anti-tumor immunity. Suppressor Of Cytokine Signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor. In the present study, we demonstrate that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which …