Faculty Bibliography

C. pyrenoidosa, a species of microalgae, has been recognized as a viable protein source for human consumption. The primary challenges in this context are the development of an efficient extraction process and the valorization of the resultant waste streams. This study, situated within the paradigm of circular economy, presents an innovative extraction approach that achieved a protein extraction efficiency of 62 %. The extracted protein exhibited remarkable oil-water emulsifying performances, such as uniform morphology with high creaming stability, suggesting a sustainable alternative to conventional emulsifiers. Additionally, hydrothermal liquefaction technique was employed for converting the residual biomass and waste solution from the extraction process into biocrude. A biocrude yield exceeding 40 wt%, characterized by a carbon content of 73 % and a higher heating value of 36 MJ/kg, were obtained. These findings demonstrate the promising potential of microalgae biorefinery, which is significant for paving toward circular economy and zero-waste society.

Widespread pain (WP) is associated with reduced function and disability. Importantly, three-fourths of the approximately 42% of U.S. adults with obesity have WP. Moreover, rates of adult obesity are higher, and WP outcomes are worse in racialized non-Hispanic Black and Hispanic/Latino/a/X groups, potentially exacerbating existing pain disparities. Bariatric surgery significantly reduces weight and improves pain. However, recurrent or unresolved pain after bariatric surgery can hinder weight loss or facilitate weight regain. The current study conducted a secondary analysis of a longitudinal study of predictors and mechanisms of weight loss after bariatric surgery to examine the point prevalence of WP and pain trajectories 24 months post surgery. Our secondary aim was to examine the association between weight loss and pain characteristics. Our exploratory aim was to longitudinally examine racial differences in pain trajectories after bariatric surgery. Our results showed that point prevalence decreased after bariatric surgery. Additionally, significant improvements in pain trajectories occurred within the first 3 months post surgery with a pattern of pain reemergence beginning at 12 months post surgery. Hispanic/Latino/a/X participants reported a higher number of painful anatomical sites before bariatric surgery, and the rate of change in this domain for this group was faster compared with the racialized non-Hispanic Black participants. These findings suggest that pain improvements are most evident during the early stages of surgical weight loss in racialized populations of adults with WP. Thus, clinicians should routinely monitor patients' weight changes after bariatric surgery as they are likely to correspond to changes in their pain experiences. PERSPECTIVE: This article presents the prevalence and pain trajectories of racialized adults with WP after surgical weight loss. Clinicians should evaluate changes in the magnitude and spatial distribution of pain after significant weight change in these populations so that pain interventions can be prescribed with greater precision.

BACKGROUND:Vice chairs (VCs) of research play an integral role in orthopaedic departments at academic medical centers; they strategically lead research efforts and support the research careers of faculty and trainees. To our knowledge, no analysis of orthopaedic VCs of research exists in the literature, and no similar analyses have been completed in other medical specialties. We aimed to investigate the academic and demographic characteristics of orthopaedic VCs of research. METHODS:Doximity was used to identify orthopaedic residencies in the U.S. Personal and program websites were queried to identify VCs of research and collect academic and demographic characteristics. The Scopus database, the National Institutes of Health (NIH) RePORTER, and Google Scholar were used to obtain each investigator's Hirsch index (h-index) and the number and type of NIH grants awarded, respectively. RESULTS:Of the 207 orthopaedic residency programs identified, 71 (34%) had a named VC of research in the orthopaedic department. Of the top 50 medical schools, 42 were affiliated with such programs. Most VCs were men (89%). The racial and/or ethnic background of the majority of VCs was White (85%), followed by Asian (14%), and Black (1%). Most held the rank of professor (78%), followed by associate professor (18%), and assistant professor (4%). Over half were PhDs (55%), followed by MDs (37%) and MD/PhDs (8%). On average, the VCs had an h-index of 40.5. Furthermore, 65% had been awarded at least 1 NIH grant for their research, with 43% awarded at least 1 R01 grant. CONCLUSIONS:VCs of research develop research opportunities and shape the brand recognition of academic orthopaedic programs. Most orthopaedic VCs of research are men (89%); 85% each are White and have a rank of professor. Nearly half have been awarded at least 1 R01 grant from the NIH. CLINICAL RELEVANCE/CONCLUSIONS:This study outlines important academic and demographic characteristics among orthopaedic surgery VCs of research. Considering the mentorship aspect of their role, VCs of research have an opportunity to influence the diversity of incoming trainees in the field of academic orthopaedics.

Tauopathies are a group of neurodegenerative diseases characterized by the presence of tau inclusions. We have developed over fifty anti-tau single-domain antibodies (sdAbs) derived from phage display libraries of a llama immunized with recombinant and pathological tau immunogens. We examined the therapeutic potential of four of these sdAbs in a Drosophila tauopathy model following their transgenic expression either in all neurons or neuronal subtypes. Three of these sdAbs showed therapeutic potential in various assays, effectively clearing pathological tau and attenuating or preventing tau-induced phenotypes that typically manifest as defects in neuronal axonal transport, neurodegeneration, functional impairments, and shortened lifespan. Of these three, one sdAb was superior in every assay, which may at least in part be attributed to its tau-binding epitope. These findings support its development as a gene therapy for tauopathies.

In vitro assays of ion transport are an essential tool for understanding molecular mechanisms associated with ATP-dependent pumps. Because ion transport is generally electrogenic, principles of electrophysiology are applicable, but conventional tools like patch-clamp are ineffective due to relatively low turnover rates of the pumps. Instead, assays have been developed to measure either voltage or current generated by transport activity of a population of molecules either in cell-derived membrane fragments or after reconstituting purified protein into proteoliposomes. In order to understand the nuances of these assays and to characterize effects of various operational parameters, we have developed a numerical model to simulate data produced by two relevant assays: fluorescence from voltage-sensitive dyes and current recorded by capacitive coupling on solid supported membranes. Parameters of the model, which has been implemented in Python, are described along with underlying principles of the computational algorithm. Experimental data from KdpFABC, a K⁺ pump associated with P-type ATPases, are presented, and model parameters have been adjusted to mimic these data. In addition, effects of key parameters such as nonselective leak conductance and turnover rate are demonstrated. Finally, simulated data are used to illustrate the effects of capacitive coupling on measured current and to compare alternative methods for quantification of raw data.

Autophagy, the major lysosomal pathway for degrading damaged or obsolete constituents, protects neurons by eliminating toxic organelles and peptides, restoring nutrient and energy homeostasis, and inhibiting apoptosis. These functions are especially vital in neurons, which are postmitotic and must survive for many decades while confronting mounting challenges of cell aging. Autophagy failure, especially related to the declining lysosomal ("phagy") functions, heightens the neuron's vulnerability to genetic and environmental factors underlying Alzheimer's disease (AD) and other late-age onset neurodegenerative diseases. Components of the global autophagy-lysosomal pathway and the closely integrated endolysosomal system are increasingly implicated as primary targets of these disorders. In AD, an imbalance between heightened autophagy induction and diminished lysosomal function in highly vulnerable pyramidal neuron populations yields an intracellular lysosomal build-up of undegraded substrates, including APP-βCTF, an inhibitor of lysosomal acidification, and membrane-damaging Aβ peptide. In the most compromised of these neurons, β-amyloid accumulates intraneuronally in plaque-like aggregates that become extracellular senile plaques when these neurons die, reflecting an "inside-out" origin of amyloid plaques seen in human AD brain and in mouse models of AD pathology. In this review, the author describes the importance of lysosomal-dependent neuronal cell death in AD associated with uniquely extreme autophagy pathology (PANTHOS) which is described as triggered by lysosomal membrane permeability during the earliest "intraneuronal" stage of AD. Effectors of other cell death cascades, notably calcium-activated calpains and protein kinases, contribute to lysosomal injury that induces leakage of cathepsins and activation of additional death cascades. Subsequent events in AD, such as microglial invasion and neuroinflammation, induce further cytotoxicity. In major neurodegenerative disease models, neuronal death and ensuing neuropathologies are substantially remediable by reversing underlying primary lysosomal deficits, thus implicating lysosomal failure and autophagy dysfunction as primary triggers of lysosomal-dependent cell death and AD pathogenesis and as promising therapeutic targets.

BACKGROUND:The purpose of the present study was to evaluate the relationships of the concentrations of pro- and anti-inflammatory biomarkers in the knee synovial fluid at the time of arthroscopic partial meniscectomy (APM) to long-term patient-reported outcomes (PROs) and conversion to total knee arthroplasty (TKA). METHODS:A database of patients who underwent APM for isolated meniscal injury was analyzed. Synovial fluid had been aspirated from the operatively treated knee prior to the surgical incision, and concentrations of pro- and anti-inflammatory biomarkers (RANTES, IL-6, MCP-1, MIP-1β, VEGF, TIMP-1, TIMP-2, IL-1RA, MMP-3, and bFGF) were quantified. Prior to surgery and again at the time of final follow-up, patients were asked to complete a survey that included a visual analog scale (VAS) for pain and Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS) questionnaires. Clustering analysis of the 10 biomarkers of interest was carried out with the k-means algorithm. RESULTS:Of the 82 patients who met the inclusion criteria for the study, 59 had not undergone subsequent ipsilateral TKA or APM, and 43 (73%) of the 59 completed PRO questionnaires at long-term follow-up. The mean follow-up time was 10.6 ± 1.3 years (range, 8.7 to 12.4 years). Higher concentrations of individual pro-inflammatory biomarkers including MCP-1 (β = 13.672, p = 0.017) and MIP-1β (β = -0.385, p = 0.012) were associated with worse VAS pain and Tegner scores, respectively. K-means clustering analysis separated the cohort of 82 patients into 2 groups, one with exclusively higher levels of pro-inflammatory biomarkers than the second group. The "pro-inflammatory phenotype" cohort had a significantly higher VAS pain score (p = 0.024) and significantly lower Lysholm (p = 0.022), KOOS-PS (p = 0.047), and Tegner (p = 0.009) scores at the time of final follow-up compared with the "anti-inflammatory phenotype" cohort. The rate of conversion to TKA was higher in the pro-inflammatory cohort (29.4% versus 12.2%, p = 0.064). Logistic regression analysis demonstrated that the pro-inflammatory phenotype was significantly correlated with conversion to TKA (odds ratio = 7.220, 95% confidence interval = 1.028 to 50.720, p = 0.047). CONCLUSIONS:The concentrations of synovial fluid biomarkers on the day of APM can be used to cluster patients into pro- and anti-inflammatory cohorts that are predictive of PROs and conversion to TKA at long-term follow-up. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUNDS/BACKGROUND:Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS:) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS:mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION/CONCLUSIONS:The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.

Proximal tubule endocytosis is essential to produce protein free urine as well as to regulate system wide metabolic pathways, such as the activation of Vitamin D. We have determined that the proximal tubule expresses an endolysosomal membrane protein, protein spinster homolog1 (Spns1), which engenders a novel iron conductance that is indispensable during embryonic development. Conditional knockout of Spns1 with a novel Cre-LoxP construct specific to megalin-expressing cells led to the arrest of megalin receptor-mediated endocytosis as well as dextran pinocytosis in proximal tubules. The endocytic defect was accompanied by changes in megalin phosphorylation as well as enlargement of lysosomes confirming previous findings in Drosophila and Zebrafish. The endocytic defect was also accompanied by iron overload in proximal tubules. Remarkably, iron levels regulated the Spns1 phenotypes, because feeding an iron deficient diet or mating Spns1 knockout with divalent metal transporter1 (DMT1) knockout rescued the phenotypes. Conversely, iron loading wild type mice reproduced the endocytic defect, These data demonstrate a reversible, negative feedback for apical endocytosis, and raise the possibility that regulation of endocytosis, pinocytosis, megalin activation, and organellar size and function is nutrient-responsive.

The translation elongation factor eEF1α (eukaryotic elongation factor 1α) mediates mRNA translation by delivering aminoacyl-tRNAs to ribosomes. eEF1α also has other reported roles, including the regulation of actin dynamics. However, these distinct roles of eEF1α are often challenging to uncouple and remain poorly understood in aging metazoan tissues. The genomes of mammals and Drosophila encode two eEF1α paralogs, with eEF1α1 expressed ubiquitously and eEF1α2 expression more limited to neurons and muscle cells. Here, we report that eEF1α2 plays a unique role in maintaining myofibril homeostasis during aging in Drosophila. Specifically, we generated an eEF1α2 null allele, which was viable and showed two distinct muscle phenotypes. In young flies, the mutants had thinner myofibrils in indirect flight muscles that could be rescued by expressing eEF1α1. With aging, the muscles of the mutant flies began showing abnormal distribution of actin and myosin in muscles, but without a change in actin and myosin protein levels. This age-related phenotype could not be rescued by eEF1α1 overexpression. These findings support an unconventional role of Drosophila eEF1α2 in age-related homeostasis of muscle myofibers.