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gabriel velez

    gabriel velez

    This chapter illustrates the diverse social identities that are developed in racial-ethnic, identity-based campus organizations. Students listed race-ethnicity as the focus of their initial attraction to these organizations. However, they... more
    This chapter illustrates the diverse social identities that are developed in racial-ethnic, identity-based campus organizations. Students listed race-ethnicity as the focus of their initial attraction to these organizations. However, they came to embed themselves in these organizations because the organizations also developed other aspects of their identities, such as their professional, political, and academic identities. This chapter also highlights students who explicitly sought to embed themselves in organizations and clubs that were not connected with their racial-ethnic identity. In doing so, this chapter takes a critical look at extracurricular activities in relation to experiences of race-ethnicity at college and examines the role they serve in minority students' self-exploration.
    . In 2020, the COVID-19 pandemic and other social dynamics created a myriad of challenges and changes for individuals, groups, and societies. The impacts on youth are particularly noteworthy given developmental processes of adolescence... more
    . In 2020, the COVID-19 pandemic and other social dynamics created a myriad of challenges and changes for individuals, groups, and societies. The impacts on youth are particularly noteworthy given developmental processes of adolescence and emerging adulthood. As psychologists, we have much to offer in studying how 2020 influenced their development and in shaping effective supports. To be useful, the work must be nuanced, iterative, and attentive to their lived realities. We argue for a dynamic research framework to study these developmental processes. Through such an approach, psychological science can provide insight into diverse young people’s experiences of COVID-19 with a focus on addressing the United Nations Sustainable Development Goals (SDGs) 3, 4, and 16 on increasing a sense of well-being, making education more equitable, and developing more peaceful societies. This paper lays out three theoretical frameworks – Synthetic, Augmentative, Generative, and Experiential, Meanings, Observations, Viewpoints, and Experiences, and the Developmental Peacebuilding Model – that can be used to capture the dynamism of meaning-making and development within changing contexts. We then provide examples from our research with young people in the United States and Ireland. This paper ends with a call for psychologists across the globe to understand and address COVID-19’s impacts on youth through iterative and integrative research methods with a focus on meaning-making. In coordination with macro-level metrics, such work can help understand lived psychosocial impacts on diverse groups of young people, while highlighting opportunities to support SDGs 3, 4, and 16.
    3DPhyloFold aligns protein structural coordinates by their alpha carbon atoms to generate a root mean square deviation (RMSD) matrix. The matrix can then be analyzed by phylogenetic reconstruction software for high-throughput protein... more
    3DPhyloFold aligns protein structural coordinates by their alpha carbon atoms to generate a root mean square deviation (RMSD) matrix. The matrix can then be analyzed by phylogenetic reconstruction software for high-throughput protein structural comparisons
    Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for... more
    Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS-CoV-2 viral entry and may represent such a target. We hypothesized drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. We created a structure-based phylogenetic computational tool 3DPhyloFold to systematically identify structurally similar serine proteases with known therapeutic inhibitors and demonstrated effective inhibition of SARS-CoV-2 infection in vitro and in vivo. Several candidate compounds, Avoralstat, PCI-27483, Antipain, and Soybean-Trypsin-Inhibitor, inhibited TMPRSS2 in biochemical and cell infection assays. Avoralstat, a clinically tested Kallikrein-related B1 inhibitor, inhibited SARS-CoV-2 entry and replication in human airway epithelial cells. In a...
    Purpose Acanthamoeba chorioretinitis is a rare manifestation of the parasitic infection, and reported cases often result in enucleation. Surgical removal of Acanthamoeba chorioretinitis has not been previously described. We report a... more
    Purpose Acanthamoeba chorioretinitis is a rare manifestation of the parasitic infection, and reported cases often result in enucleation. Surgical removal of Acanthamoeba chorioretinitis has not been previously described. We report a surgical case of Acanthamoeba chorioretinitis spread from keratitis that ultimately resulted in a disease-free outcome. Observations A healthy 80-year-old male with a history of keratoconus requiring a penetrating keratoplasty in the fellow eye presented with a severe corneal ulcer clinically consistent with Acanthamoeba keratitis. He ultimately required a penetrating keratoplasty and improved clinically until he developed vitritis on post-operative month 1 and was diagnosed with endophthalmitis. B-scan ultrasound demonstrated vitreous opacities and a large retinal mass that reduced in size following serial intravitreal injections of antibiotics, oral antibiotics, and a limited pars plana vitrectomy. He underwent a repeat pars plana vitrectomy 6 weeks later and a retinal mass in the mid-periphery with an associated tractional retinal detachment was noted. A localized retinectomy was performed around the lesion which was excised entirely, and silicone oil was instilled. Pathology of the lesion showed acute and chronic granulomatous necrotizing inflammation with the presence of several definitive amoebic organisms and numerous cells suspicious for amoebae. The patient was maintained on oral antibiotics by the Infectious Disease Service and was disease-free 1-year post-infection. Conclusions and importance Acanthamoeba chorioretinitis is a rare, devastating disease and often leads to enucleation. We present a surgical case showing control of the infection utilizing a surgical retinectomy. Aggressive local therapy and a multidisciplinary approach with the Infectious Disease Service may lead to a successful outcome.
    Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for... more
    Ocular disorders originating in the retina can result in a partial or total loss of vision, making drug delivery to the retina of vital importance. However, effectively delivering drugs to the retina remains a challenge for ophthalmologists due to various anatomical and physicochemical barriers in the eye. This review introduces diverse administration routes and the accordant pharmacokinetic profiles of ocular drugs to aid in the development of safe and efficient drug delivery systems to the retina with a focus on peptidomimetics as a growing class of retinal drugs, which have great therapeutic potential and a high degree of specificity. We also discuss the pharmacokinetic profiles of small molecule drugs due to their structural similarity to small peptidomimetics. Lastly, various formulation strategies are suggested to overcome pharmacokinetic hurdles such as solubility, retention time, enzymatic degradation, tissue targeting, and membrane permeability. This knowledge can be used t...
    Field social psychology is a conceptual and methodological approach to describe, examine, and explain psychological phenomena at multiple levels of analysis with emphasis on the sociocultural environments in which people are embedded, the... more
    Field social psychology is a conceptual and methodological approach to describe, examine, and explain psychological phenomena at multiple levels of analysis with emphasis on the sociocultural environments in which people are embedded, the unfolding of psychological processes over time, and the use of ecologically valid multiple methods in conjunction. In this essay, we first define a contemporary form of field social psychology from its roots in the history of psychological study. Second, we argue for the necessity of the reemergence of this approach given the limitations of the dominant current social psychological paradigm exposed by the replication crisis. Third, we outline an integrative and actionable model of field social psychological research. We describe two contemporary examples of field social psychological research concerning climate change protests in Norway and restorative justice in the U.S.A. to illustrate this framework. We end with implications of field social psychology for developing psychological science. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
    Academia is often critiqued as an “ivory tower” where research, thinking, and teaching are isolated from the complexity and everyday experience of so many people. As instructors of political and other psychology courses, we strive to... more
    Academia is often critiqued as an “ivory tower” where research, thinking, and teaching are isolated from the complexity and everyday experience of so many people. As instructors of political and other psychology courses, we strive to break down these barriers and engage with the dynamic and nuanced nature of phenomena as situated in lived social and political contexts. In this report, we unpack and detail how we strive to achieve this goal by expanding on Plous’ articulation of action teaching (2012). We first define our pedagogical focus on active engagement, critical thinking, and staying on the move between multiple perspectives. We then provide specific examples of how we enact our philosophy in activities and assessment. We end by articulating how this approach to teaching in social and political psychology can be understood as furthering not only our students’ intellectual growth as psychologists, but also their development as democratic citizens. In doing so, we argue that ac...
    Social psychologists are often criticized for failing to capture the dynamic nature of psychological processes. We present a novel framework to address this problem. The MOVE framework contends that to comprehend complex, contradictory,... more
    Social psychologists are often criticized for failing to capture the dynamic nature of psychological processes. We present a novel framework to address this problem. The MOVE framework contends that to comprehend complex, contradictory, and divergent patterns of thought, affect, and behavior within changing, real-world contexts, it is necessary to undertake ecologically valid research that is attentive to the lived experiences and meaning-making processes of culturally embedded individuals over time. A focus on meanings, observations, viewpoints, and experiences is essential for social psychological research that holistically captures how people construct, understand, respond, position, and act over time within changing social, economic, and political contexts. To illustrate the utility of our proposition, we draw on classic social psychological studies and multimethod fieldwork during a period of rapid social and political change in Colombia during the peace process (2012–2017). We...
    For emerging adults transitioning to college, normative social and contextual shifts present challenges that are largely a productive aspect of development. But not all students have the same experiences, nor do all students manage... more
    For emerging adults transitioning to college, normative social and contextual shifts present challenges that are largely a productive aspect of development. But not all students have the same experiences, nor do all students manage similar experiences in similar ways. Black and Latinx emerging adults transitioning to Historically White Institutions must adjust not only to college life but also to feeling different and, sometimes, isolated. There is a dearth of qualitative work examining how students of color make meaning of their racial-ethnic experiences on campus. Our article draws on a mixed-methods study of Black and Latinx emerging adults’ transition to college to investigate how high school racial-ethnic contexts shape students’ interpretations of experiences of difference on college campuses. There was substantial variation in how Black and Latinx students interpreted experiences of difference on campus and coped with their feelings of otherness, and this variation was predic...
    Neurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses... more
    Neurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses to the loss of the entire neural retinal network. We previously found that proteomic analysis of the adjacent vitreous serves as way to indirectly biopsy the neural retina and identify changes in the retinal proteome. We therefore analyzed protein expression in liquid vitreous biopsies from autosomal recessive retinitis pigmentosa (arRP) patients with PDE6A mutations and arRP mice with Pde6ɑ mutations. Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor cell death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Dietary supplementation...
    Significance Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease that presents with bone destruction occurring primarily in children. In a mouse ENU mutagenesis screen, the Ali18 strain was isolated... more
    Significance Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease that presents with bone destruction occurring primarily in children. In a mouse ENU mutagenesis screen, the Ali18 strain was isolated because of spontaneous inflammation in the joints and bones. Sequencing candidate genes in the Ali18 critical region identified a missense mutation in the C-terminal regulatory region of the Src family kinase (SFK) member, Fgr . Genome editing revealed Fgr dependency of the inflammatory phenotype in Ali18 mice. Further, whole exome sequencing in our CRMO cohort identified two patients with missense mutations in FGR . In vitro functional assays confirm altered protein function. This work identifies FGR as a CRMO susceptibility gene and suggests that targeting SFKs may be useful in its treatment.
    Compound heterozygotes occur when different mutations at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of mutations at the individual level. We... more
    Compound heterozygotes occur when different mutations at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of mutations at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 genomes participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or Infantile Spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 genomes data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 genomes participants using minor allele frequency (MAF) cutoffs of 0.5% and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous mutati...
    BACKGROUND AND OBJECTIVE To describe a novel surgical technique using pars plana vitrectomy (PPV), internal limiting membrane (ILM) abrasion, and intravitreal fibrin glue for the treatment of optic disc pit maculopathy. PATIENTS AND... more
    BACKGROUND AND OBJECTIVE To describe a novel surgical technique using pars plana vitrectomy (PPV), internal limiting membrane (ILM) abrasion, and intravitreal fibrin glue for the treatment of optic disc pit maculopathy. PATIENTS AND METHODS Surgical case series technique with scanning electron microscopy (SEM) of human post-mortem eyes. RESULTS Using SEM, the authors demonstrate the persistent adherence of vitreous fragments to the optic disc following induction of posterior vitreous detachment in human postmortem eyes. The authors describe a surgical technique using PPV, Tano Diamond Dusted Membrane Scraper for an ILM abrasion, intravitreal fibrin glue (Tisseel), and gas-air exchange to seal optic disc pits. The authors report successful long-term visual and anatomical outcomes in three patients. CONCLUSIONS Intravitreal fibrin glue, when combined with ILM abrasion, may be a viable treatment option for optic disc pit maculopathy with good short- and long-term visual acuity outcomes. SEM shows that ILM abrasion removes vitreous fragments, which are persistently adherent and may lead to failure with other interventional techniques. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e271-e277.].
    SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout models, it has been postulated... more
    SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was found to play a major role in repulsive midline axon guidance in central nervous system development. Based on studies utilizing knockout models, it has been postulated that SLIT2 is important for preventing inappropriate axonal routing during mammalian optic chiasm development. Case report. Here, we report a case of congenital myopia, anisometropia, and obesity in a patient with a SLIT2 point mutation. Examination of the patient's skin biopsy revealed abnormalities in elastin and collagen fibrils that suggest an underlying connective tissue disorder. Structural modeling placed the novel mutation (p.D1407G) in the EGF-like domain 8 and was predicted to affect interactions with SLIT2 binding partners. To the authors' knowledge, this is the first report of a SLIT2 variant in the context of these ocular findings.
    Mutations that activate the protease calpain-5 ( cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We... more
    Mutations that activate the protease calpain-5 ( cause a nonsyndromic adult-onset autoinflammatory eye disease characterized by uveitis, altered synaptic signaling, retinal degeneration, neovascularization, and intraocular fibrosis. We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation that links mutation severity to proteolytic activity and the possibility of earlier onset syndromic disease with auditory and neurological abnormalities.
    Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the ability of the inner retina to manage metabolic waste and oxidative stress is unknown. Proteomic analysis of antioxidants in the human vitreous, the... more
    Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the ability of the inner retina to manage metabolic waste and oxidative stress is unknown. Proteomic analysis of antioxidants in the human vitreous, the extracellular matrix opposing the inner retina, identified superoxide dismutase-3 (SOD3) that localized to a unique matrix structure in the vitreous base and cortex. To determine the role of SOD3, Sod3 mice underwent histological and clinical phenotyping. Although the eyes were structurally normal, at the vitreoretinal interface Sod3 mice demonstrated higher levels of 3-nitrotyrosine, a key marker of oxidative stress. Pattern electroretinography also showed physiological signaling abnormalities within the inner retina. Vitreous biopsies and epiretinal membranes collected from patients with diabetic vitreoretinopathy (DVR) and a mouse model of DVR showed significantly higher levels of nitrates and/or 3-nitrotyrosine oxidative stress biomarkers suggestive of S...
    Beginning with Erikson, identity formation has often been framed as a salient developmental challenge for adolescents. Recent theoretical advances situate this identity formation as a central life course process involving ecological and... more
    Beginning with Erikson, identity formation has often been framed as a salient developmental challenge for adolescents. Recent theoretical advances situate this identity formation as a central life course process involving ecological and social context associated with diverse experiences and characteristics. Some scholars have employed intersectionality as a call to study experiences of individuals who belong to multiple marginalized groups. In this article, we argue that developmental research would be served by a return to Crenshaw's formulation of intersectionality-that is, that marginalization involves systematic inequality and interlocking systems of oppression-as integrated with Spencer's phenomenological variant of ecological systems theory (PVEST). The latter was formulated as a needed critique of traditional developmental theories that generally ignored the problem of inequality as experienced through multiple layers of navigated contexts. Problematic ecological cont...
    Differences in regional protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like age-related macular degeneration, cystoid macular edema, retinitis pigmentosa, and... more
    Differences in regional protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like age-related macular degeneration, cystoid macular edema, retinitis pigmentosa, and diabetic retinopathy. To quantify protein levels in the human retina and identify patterns of differentially-expressed proteins, we collected foveomacular, juxta-macular, and peripheral retina punch biopsies from healthy donor eyes and analyzed protein content by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein expression was analyzed with 1-way ANOVA, gene ontology, pathway representation, and network analysis. We identified a mean of 1,974 proteins in the foveomacular retina, 1,999 in the juxta-macular retina, and 1,779 in the peripheral retina. Six hundred ninety-seven differentially-expressed proteins included those unique to and abundant in each anatomic region. Proteins with higher expression in each region include: heat-shock p...
    The human retina is composed of the sensory neuroretina and the underlying retinal pigmented epithelium (RPE), which is firmly complexed to the vascular choroid layer. Different regions of the retina are anatomically and molecularly... more
    The human retina is composed of the sensory neuroretina and the underlying retinal pigmented epithelium (RPE), which is firmly complexed to the vascular choroid layer. Different regions of the retina are anatomically and molecularly distinct, facilitating unique functions and demonstrating differential susceptibility to disease. Proteomic analysis of each of these regions and layers can provide vital insights into the molecular process of many diseases, including Age-Related Macular Degeneration (AMD), diabetes mellitus, and glaucoma. However, separation of retinal regions and layers is essential before quantitative proteomic analysis can be accomplished. Here, we describe a method for dissection and collection of the foveal, macular, and peripheral retinal regions and underlying RPE-choroid complex, involving regional punch biopsies and manual removal of tissue layers from a human eye.One-dimensional SDS-PAGE as well as downstream proteomic analysis, such as liquid chromatography-t...
    Hyperopia (farsightedness) is a common and significant cause of visual impairment, and extreme hyperopia (nanophthalmos) is a consequence of loss-of-function MFRP mutations. MFRP deficiency causes abnormal eye growth along the visual axis... more
    Hyperopia (farsightedness) is a common and significant cause of visual impairment, and extreme hyperopia (nanophthalmos) is a consequence of loss-of-function MFRP mutations. MFRP deficiency causes abnormal eye growth along the visual axis and significant visual comorbidities, such as angle closure glaucoma, cystic macular edema, and exudative retinal detachment. The Mfrp rd6 /Mfrp rd6 mouse is used as a pre-clinical animal model of retinal degeneration, and we found it was also hyperopic. To test the effect of restoring Mfrp expression, we delivered a wild-type Mfrp to the retinal pigmented epithelium (RPE) of Mfrp rd6 /Mfrp rd6 mice via adeno-associated viral (AAV) gene therapy. Phenotypic rescue was evaluated using non-invasive, human clinical testing, including fundus auto-fluorescence, optical coherence tomography, electroretinography, and ultrasound. These analyses showed gene therapy restored retinal function and normalized axial length. Proteomic analysis of RPE tissue reveal...
    To profile vitreous cytokine expression of proliferative vitreoretinopathy (PVR) patients. Case-control study. Liquid biopsies were collected from 2 groups: control subjects (n = 3) undergoing pars plana vitrectomy to remove an epiretinal... more
    To profile vitreous cytokine expression of proliferative vitreoretinopathy (PVR) patients. Case-control study. Liquid biopsies were collected from 2 groups: control subjects (n = 3) undergoing pars plana vitrectomy to remove an epiretinal membrane (ERM), and test subjects (n = 7) with varying degrees of PVR. A high-throughput cytokine screen measured expression of 200 cytokines. Cytokine expression patterns were prospectively validated in separate cohorts of control patients and those with PVR-A, PVR-B, and PVR-C (n = 10 for each group). Expression changes were evaluated by analysis of variance (significant P value < .05), hierarchical cluster algorithm, and pathway analysis, to identify candidate pathways for prospective studies. In PVR vitreous, 29 cytokines were upregulated compared to controls. Early PVR vitreous showed upregulation of T-cell markers, profibrotic cytokines, and cytokines downstream of mTOR activation (IL-2, IL-6, and IL-13), whereas in late PVR vitreous, cyto...
    In patients with limited response to conventional therapeutics, repositioning of already approved drugs can bring new, more effective options. Current drug repositioning methods, however, frequently rely on retrospective computational... more
    In patients with limited response to conventional therapeutics, repositioning of already approved drugs can bring new, more effective options. Current drug repositioning methods, however, frequently rely on retrospective computational analyses and genetic testing - time consuming methods that delay application of repositioned drugs. Here, we show how proteomic analysis of liquid biopsies successfully guided treatment of neovascular inflammatory vitreoretinopathy (NIV), an inherited autoinflammatory disease with otherwise poor clinical outcomes. Vitreous biopsies from NIV patients were profiled by an antibody array for expression of 200 cytokine-signaling proteins. Non-NIV controls were compared with NIV samples from various stages of disease progression. Patterns were identified by 1-way ANOVA, hierarchical clustering, and pathway analysis. Subjects treated with repositioned therapies were followed longitudinally. Proteomic profiles revealed molecular pathways in NIV pathologies and...
    We propose a SAGE model for social psychological research. Encapsulated in our acronym is a proposal to have a synthetic approach to social psychological research, in which qualitative methods are augmentative to quantitative ones,... more
    We propose a SAGE model for social psychological research. Encapsulated in our acronym is a proposal to have a synthetic approach to social psychological research, in which qualitative methods are augmentative to quantitative ones, qualitative methods can be generative of new experimental hypotheses, and qualitative methods can capture experiences that evade experimental reductionism. We remind social psychological researchers that psychology was founded in multiple methods of investigation at multiple levels of analysis. We discuss historical examples and our own research as contemporary examples of how a SAGE model can operate in part or as an integrated whole. The implications of our model are discussed.
    The current study investigates the utility of political activism as a protective factor against experiences of racial/ethnic (R/E) discrimination that negatively affect stress, anxiety, and depressive symptoms among Black and Latinx... more
    The current study investigates the utility of political activism as a protective factor against experiences of racial/ethnic (R/E) discrimination that negatively affect stress, anxiety, and depressive symptoms among Black and Latinx college freshmen at predominately White institutions. Data come from the Minority College Cohort Study, a longitudinal investigation of Black and Latinx college students (N = 504; 44% Black). We conducted multiple regression analyses for each mental health indicator and tested for interaction effects. For Black and Latinx students, the relationship between R/E microaggressions and end of freshman year stress varied by political activism. For Black students, the relationship between R/E microaggressions and end of the year anxiety varied by political activism. There was a significant interaction effect for depressive symptoms among Latinx students. Political activism serves as a protective factor to mitigate the negative effect of R/E discrimination on st...
    To report a case of elevated intraocular pressure with retinal detachment. Liquid chromatography and tandem mass spectrometry was performed on the patient aqueous biopsy. Protein levels were analyzed with 1-way analysis of variance... more
    To report a case of elevated intraocular pressure with retinal detachment. Liquid chromatography and tandem mass spectrometry was performed on the patient aqueous biopsy. Protein levels were analyzed with 1-way analysis of variance (ANOVA) and unbiased clustering. High levels of rod outer segment proteins were not detected, suggesting that this was not a case of Schwartz-Matsuo syndrome. Instead, elevated levels of Hepcidin (HEPC) and Cystatin C (CYTC; candidate biomarkers for primary open angle glaucoma) were detected, suggesting a different, unknown etiology. Molecular diagnoses can differentiate between clinical diagnoses and point to common biomarkers or disease mechanisms.
    Foveal hypoplasia (FH) in the absence of albinism, aniridia, microphthalmia, or achromatopsia is exceedingly rare, and the molecular basis for the disorder remains unknown. FH is characterized by the absence of both the retinal foveal pit... more
    Foveal hypoplasia (FH) in the absence of albinism, aniridia, microphthalmia, or achromatopsia is exceedingly rare, and the molecular basis for the disorder remains unknown. FH is characterized by the absence of both the retinal foveal pit and avascular zone, but with preserved retinal architecture. SLC38A8 encodes a sodium-coupled neutral amino acid transporter with a preference for glutamate as a substrate. SLC38A8 has been linked to FH. Here, we describe a novel mutation to SLC38A8 which causes FH, and report the novel use of OCT-angiography to improve the precision of FH diagnosis. More so, we used computational modeling to explore possible functional effects of known SLC38A8 mutations. Fundus autofluorescence, SD-OCT, and OCT-angiography were used to make the clinical diagnosis. Whole-exome sequencing led to the identification of a novel disease-causing variant in SLC38A8. Computational modeling approaches were used to visualize known SLC38A8 mutations, as well as to predict mut...
    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two... more
    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents. Microarray analysis of bone marrow macrophages from the CRMO murine model (cmo) determined that the Fblim1 ortholog is the most differentially expressed gene, downregulated over 20-fold in the cmo mouse. We sequenced FBLIM1 in 96 CRMO subjects and found a second proband with a novel frameshift mutation in exon 6 and a rare regulatory variant. In SaOS2 cells, overexpressing the regulatory mutation showed the flanking region acts as an enhance...
    Calpain-5 is a calcium-activated protease expressed in the retina. Mutations in calpain-5 cause autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM#193235). The structure of calpain-5 has not been determined, thus... more
    Calpain-5 is a calcium-activated protease expressed in the retina. Mutations in calpain-5 cause autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM#193235). The structure of calpain-5 has not been determined, thus hindering the investigation of its proteolytic targets and pathological role in ADNIV. Herein, we report models of the proteolytic core of calpain-5 (mini-calpain-5) containing two globular domains (termed DIIa-IIb) connected by a short, flexible linker, consistent with small-angle X-ray scattering (SAXS) data. Structural modeling in the absence of calcium suggests that mini-calpain-5 adopts a more open conformation when compared to previously determined structures of other calpain cores. This open conformation, achieved by a rotation of DIIa and DIIb with respect to each other, prevents formation of the active site and constrains the enzyme in an inactivated form. The relative domain rotation of 60-100° we found for mini-calpain-5 (a non-classical c...

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