Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Cell Biology
Total Results:
14202
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2026:123(2).DOI: 10.1073/pnas.2500723123
Elevator mechanism dynamics in a sodium-coupled dicarboxylate transporter
VcINDY, the sodium-dependent dicarboxylate transporter from
PMID: 41490488
ISSN: 1091-6490
CID: 5980652
Population analysis and immunologic landscape of melanoma in people living with HIV
PURPOSE/OBJECTIVE:To dissect the clinical and immunological features of people living with HIV (PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer. EXPERIMENTAL DESIGN/METHODS:We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n=11), with downstream validation using multiplex immunofluorescence (n=15 PLWH, n=14 PLw/oH). RESULTS:PLWH were diagnosed at a younger age, had greater representation of Hispanic and Black individuals, and showed reduced survival. They also had a markedly increased risk of brain metastases. PLWH experienced significant delays in initiating immune checkpoint inhibitor (ICI) therapy and had worse post-ICI survival, even after balancing covariates. Spatial transcriptomics revealed a more immunosuppressive tumor microenvironment in PLWH, with increased transcription of immune checkpoints (PD1, LAG3) and reduced antigen-presentation markers (HLA-DRB, B2M), with distinct spatial distributions in tumors and surrounding microenvironments. Multiplex immunofluorescence demonstrated features of an exhausted CD8⁺ T cell compartment, including enrichment of PD1intLAG3⁻ and PD1intLAG3⁺ subpopulations, and a significant accumulation of myeloid-derived suppressor cells (CD11b⁺ HLA-DR⁻ CD33⁺). CONCLUSIONS:Melanoma in PLWH is associated with distinct clinical and immunological features, including delayed ICI treatment, reduced survival, and an immunosuppressive microenvironment with exhausted CD8⁺ T cells and expanded myeloid-derived suppressor cells. These findings suggest that chronic HIV infection may impair antitumor immunity in melanoma. Targeting the pathways identified here may improve therapeutic responses and outcomes in this population.
PMID: 41504629
ISSN: 1557-3265
CID: 5981192
European journal of orthopaedic surgery & traumatology = orthopedie traumatologie. 2026:36(1).DOI: 10.1007/s00590-025-04588-8
Inpatient mortality following hip fracture in the United States: an updated analysis of over one million cases
BACKGROUND:Understanding the current risk of inpatient mortality following hip fracture in the United States is of significant value to patient families and the health system. Currently, the literature lacks a national representation of the inpatient mortality following hip fracture. PURPOSE/OBJECTIVE:The purpose of this study was to investigate the incidence of inpatient mortality following hip fracture using Epic Cosmos-an aggregated, de-identified, multi-institutional data that includes over 280 million patients in the United States. METHODS:A "Cosmos hip fracture cohort" that included all adults (18 years or older) who sustained a femoral neck, intertrochanteric, or subtrochanteric hip fracture (ICD 72.0, S72.1, S72.2) between January 2019 and December 2024 was created. The dataset was queried for demographic data including age, sex, geographic location, incidence of inpatient mortality, and bone health medication use at the time of admission. RESULTS:The Cosmos database included 284,455,033 patients, of which 1,232,250 hip fracture hospital admissions between January 2019 and December 2024 were identified. Of these patients, 47,773 (3.9%) expired during their hip fracture hospital admission. The most common age bracket was 85 years or older (39.8%), followed by 75-85 (30.0%), and 65-75 (17.8%). Most patients were white (91%) females (55.5%). Most inpatient mortalities occurred in the South (38.4%), followed by the Midwest (31.8%), followed by the Northeast (23.6%), and last by the West (6.2%). CONCLUSION/CONCLUSIONS:The current inpatient mortality following hip fracture is 3.9%. Most inpatient mortalities occurred in white females above the age of 85 in the South of the country. LEVEL OF EVIDENCE/METHODS:Level III.
PMID: 41493636
ISSN: 1432-1068
CID: 5980802
Proximal Implant Breakage after Cephalomedullary Nailing of Extra-capsular Proximal Femur Fractures: A Multi-Center Retrospective Comparative Analysis
OBJECTIVE:To compare rates of nail breakage of three common cephalomedullary nails (CMNs) for the treatment of AO/OTA 31A1-3 femur fractures. METHODS:Design: multi-center retrospective study. SETTING/METHODS:13 Level I trauma centers. PATIENT SELECTION CRITERIA/UNASSIGNED:Adult patients with AO/OTA 31A1-3 femur fractures treated between 2014 and 2021with the Trochanteric Fixation Nail-Advanced (TFNA), Gamma3, or Trigen InterTAN were included. OUTCOME MEASUREMENTS AND COMPARISONS/UNASSIGNED:The primary outcome was implant (nail or head element) breakage. The secondary outcomes included nonunion, cut-out/cut-through and overall reoperation rate. Univariate and multivariable analyses were performed to compare breakage rates between implants while controlling for age, sex, AO/OTA 31A1-2 vs 31A3 fracture patterns, low vs high-energy mechanisms and post-operative neck shaft angle (NSA). RESULTS:2,130 patients were included: 770 (36.2%) TFNA, 1,073 (50.4%) Gamma3 and 287 (13.5%) InterTAN. The InterTAN group had younger patients (median age: InterTan: 74, TFNA: 77, Gamma3: 80, p<0.001), more high-energy mechanisms (InterTan: 23%, TFNA: 14%, Gamma3: 10%, p=0.001), and more varus malreductions (NSA<128.5: InterTan: 46%, Gamma3: 39%, TFNA: 34%, p=0.001). The TFNA group was more likely to have an AO/OTA 31A3 fracture pattern than the Gamma3 (TFNA: 17.3%, InterTAN: 14.3%, Gamma3: 12.1%, p=0.002). The overall rate of implant breakage was 1.4% in the InterTAN group, 1.2% in the TFNA group, and 0% in the Gamma3 group. All breakages occurred in the presence of a nonunion or delayed union. Only two of the 31A3 fracture patterns resulted in breakage, both in the TFNA group, while the remainder occurred in 31A1-2 fracture patterns (p = 1.0). After controlling for confounding factors listed above, the TFNA and InterTAN groups were associated with a marginally increased odds of implant breakage compared to the Gamma3 (TFNA vs Gamma3: OR 0.04, 95% CI <0.01-0.5, p=0.034; InterTAN vs Gamma3: OR 0.04, 95% CI <0.01-0.5, p=0.037), while there was no difference between the TFNA and InterTAN (p=0.991). Post-operative neck shaft angle was not independently predictive of breakage (p = 0.55). CONCLUSIONS:This study suggests that the TFNA may be slightly more prone to breakage than the Gamma3 when used for extracapsular proximal femur fractures. However, breakage is a rare event after cephalomedullary nailing with all implants evaluated, is always associated with nonunion or delayed union, and the magnitude of this difference may not be clinically relevant. LEVEL OF EVIDENCE/METHODS:III.
PMID: 41493187
ISSN: 1531-2291
CID: 5980762
On the mechanism of K+ transport through the inter-subunit tunnel of KdpFABC
KdpFABC is an ATP-dependent membrane complex that enables prokaryotes to maintain potassium homeostasis under potassium-limited conditions. It features a unique hybrid mechanism combining a channel-like selectivity filter in KdpA with the ATP-driven transport functionality of KdpB. A key unresolved question is whether K+ ions translocate through the inter-subunit tunnel as a queue of ions or individually within a hydrated environment. Using molecular dynamics simulations, metadynamics, anomalous X-ray scattering, and biochemical assays, we demonstrate that the tunnel is predominantly occupied by water molecules rather than multiple K+ ions. Our results identify only one stable intermediate binding site for K+ within the tunnel, apart from the canonical sites in KdpA and KdpB. Free energy calculations reveal a substantial barrier (∼22 kcal/mol) at the KdpA-KdpB interface, making spontaneous K+ translocation unlikely. Furthermore, mutagenesis and functional assays confirm previous findings that Phe232 at this interface plays a key role in coupling ATP hydrolysis to K+ transport. These findings challenge previous models containing a continuous wire of K+ ions through the tunnel and suggest the existence of an as-yet unidentified intermediate state or mechanistic detail that facilitates K+ movement into KdpB.
PMID: 41384914
ISSN: 1540-7748
CID: 5978042
Non-coding RNAs in lipid metabolism and their roles in atherosclerosis
The discovery of non-coding RNAs has expanded our understanding of how genetic features are linked to cellular function. The illumination of this so-called dark matter of the genome has revealed new categories of RNA with essential roles in the regulation of protein-coding genes and genome organization. In particular, microRNAs and long non-coding RNAs have emerged as important regulators of cardiovascular health and disease. In this Review, we summarize our current understanding of the mechanisms and functional roles of microRNAs and long non-coding RNAs in the regulation of lipid homeostasis, vascular biology and atherosclerosis. We discuss how interruption of non-coding RNA regulatory circuits influence lipoprotein metabolism in the liver and the circulation, as well as the effects of non-coding RNAs on inflammatory processes in the artery wall that contribute to atherosclerotic plaque formation. Finally, we highlight potential opportunities to harness non-coding RNAs as biomarkers and targeted therapeutics for atherosclerotic cardiovascular disease.
PMID: 41478885
ISSN: 1759-5010
CID: 6001262
Integrin is required for basement membrane crossing and branching of an invading intracellular tube
The narrowest biological tubes are comprised of cells that hollow to form an intracellular lumen. Here, we examine early lumenogenesis of the C. elegans excretory cell, which branches to form an H-shaped intracellular tube spanning the length of the worm. Using genetically paralyzed embryos to freeze movement, we describe lumen initiation and branching for the first time using time-lapse fluorescence microscopy. We show that the excretory cell lumen forms through a plasma membrane invasion mechanism when a nascent lumen grows from the plasma membrane into the cytoplasm. The lumen subsequently extends along the left-right axis before branching to form anterior-posterior projections. Through a genetic screen, we identify mutations in ina-1/⍺-integrin and pat-3/β-integrin that block lumenogenesis at the anterior-posterior branching step, and we show that integrin function is required within the excretory cell. Finally, we find that the excretory cell crosses the epidermal basement membrane where anterior-posterior branches form and demonstrate that basement membrane crossing fails in integrin mutant embryos. Our findings reveal how an intracellular lumen initiates and branches and identify integrins and basement membrane as key branching regulators.
PMID: 41321174
ISSN: 1477-9129
CID: 5974502
Palaeometabolomes yield biological and ecological profiles at early human sites
The science of metabolic profiling exploits chemical compound byproducts of metabolism called metabolites1 that explain internal biological functions, physiological health and disease, and provide evidence of external influences specific to an organism's habitat. Here we assess palaeometabolomes from fossilized mammalian hard tissues as a molecular ecological strategy to provide evidence of an ancient organism's relationship with its environment. From eastern, central and southern African Plio-Pleistocene localities of palaeoanthropological significance, we study six fossils from Olduvai Gorge, Tanzania, one from the Chiwondo Beds, Malawi, and one from Makapansgat, South Africa. We perform endogeneity assessments by analysing palaeometabolomes of palaeosols and the effects of owl digestion on rodent bones to enable prudent ecological inferences. Diagenesis is indicated by metabolites of collagenase-producing bacteria2, whereas the preservation of peptides including those of collagen are identified by proteomics. Endogenous metabolites document biological functions and exogenous metabolites render environmental details including soil characteristics and woody cover, and enable annual minimum and maximum rainfall and temperature reconstructions at Olduvai Gorge, supporting the freshwater woodland and grasslands of Olduvai Gorge Bed I3-5, and the dry woodlands and marsh of Olduvai Gorge Upper Bed II6. All sites denote wetter and/or warmer conditions than today. We infer that metabolites preserved in hard tissues derive from an extravasated vasculature serum filtrate that becomes entombed within developing mineralized matrices, and most probably survive palaeontological timeframes in the nanoscopic 'pool' of structural-bound water that occurs in hard tissue niches7.
PMID: 41407854
ISSN: 1476-4687
CID: 5979502
Journal of child psychology & psychiatry & allied disciplines. 2026:67(1):104-114.DOI: 10.1111/jcpp.70023
Motor stereotypies in toddlers with and without autism: A transdiagnostic dimension
BACKGROUND:Motor stereotypies (MS) represent one of the transdiagnostic symptom dimensions identified by the NIMH Research Domain Criteria work group as relevant to psychopathology. MS are common in neurodevelopmental conditions, but they remain poorly understood, particularly in early childhood. The present study examined MS in 648 toddlers with autism spectrum disorder (autism, n = 455) and other neurodevelopmental conditions (non-autism, n = 193) and their concurrent and prospective links with other phenotypic characteristics. METHODS:Toddlers were recruited between February 2000 and October 2018 and evaluated at 24 +/- 5 months (Time 1, N = 648) and 41 +/- 6 months (Time 2, N = 455). The presence of MS was determined based on the Autism Diagnostic Observation Schedule assessment. The phenotypic measures included adaptive socialization skills, severity of social symptoms of autism, and verbal, nonverbal, and motor skills. The analysis was conducted using the general linear models while controlling for age, sex, visit year, group, and other relevant covariates. RESULTS: CONCLUSIONS:Motor stereotypies are present in toddlers with and without autism and may represent a distinct transdiagnostic dimension expressed early in development, associated with core developmental skills and, putatively, characterized by shared pathophysiology across neurodevelopmental conditions.
PMID: 40757458
ISSN: 1469-7610
CID: 5904782
Lichen planopilaris in children: Clinical characteristics, comorbidities, and treatment outcomes in a single-center case series [Case Report]
PMCID:12769417
PMID: 41502839
ISSN: 2352-5126
CID: 5981102
