Research Letter: Characterizing Lifetime Mild TBI Exposure Among Female and Male Military Service Members and Veterans in the LIMBIC-CENC Study.

OBJECTIVE: To (1) characterize lifetime mild traumatic brain injury (TBI) exposures among male and female US military service members and Veterans (SMVs) and (2) evaluate sex-related differences in mild TBI exposures. SETTING: Clinical research laboratory. PARTICIPANTS: Participants were enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC) Prospective Longitudinal Study. DESIGN: Cross-sectional. MAIN MEASURES: Lifetime history of mild TBI was measured via structured interview. All mild TBI characteristics were collected as part of this interview, including total lifetime number; environment (deployment vs. non-deployment); timing of injury (relative to military service and age); and mechanism of injury (blast-related vs. non-blast). RESULTS: Most participants (n = 2323; 87.5% male; 79.6% Veteran) reported ≥1 lifetime mild TBI (n = 1912; 82%), among whom, many reported ≥2 lifetime mild TBIs. Female SMVs reported fewer total lifetime mild TBIs than male participants (P < 0.001), including fewer deployment-related (P < 0.001) and non-deployment (P < 0.001) mild TBIs. There were significant sex differences for total number of mild TBIs sustained before (P = 0.005) and during (P < 0.001) military service but not after separation from military service (P = 0.99). Among participants with a lifetime history of mild TBI, female SMVs were less likely to report ≥2 mTBIs (P = 0.003); however, male SMVs were more likely to report a mild TBI during military service (P = 0.03), including combat-related mild TBI (P < 0.001) and mild TBI involving blast (P < 0.001). CONCLUSIONS: These findings inform clinical and research efforts related to mild TBI in US military SMVs. It may not be sufficient to simply measure the total number of mild TBIs when seeking to compare clinical outcomes related to mild TBI between sexes; rather, it is important to measure and account for the timing, environment, and mechanisms associated with mild TBIs sustained by female and male SMVs.

Protocol for optimizing surface expression and speed in coaggregation assays using K562 cells and subsequent analysis with a CoAg Index.

Coaggregation assays using K562 cells have been extensively employed to study how cell adhesion molecules mediate specificity between different populations. Here we describe how to prepare K562 cells, optimize electroporation conditions, calibrate antibodies used for protein detection, determine the surface expression of desired adhesion molecules, and considerations for the rotational force to be applied during the assay. We also detail procedures for analyzing coaggregates using our established CoAggregation (CoAg) Index. For complete details on the use and execution of this protocol, please refer to Bisogni et al.1.

Thermochemical Properties of High Pressure Neodymium Monoxide.

Neodymium monoxide (NdO) is a metastable rare earth oxide material with a unique electronic structure, which has potential applications across various fields such as semiconductors, energy, catalysis, laser technology, and advanced communications. Despite its promising attributes, the thermodynamic properties of NdO remain unexplored. In this study, high pressure, high temperature phases of neodymium monoxide (NdO, with a rocksalt structure) and body-centered cubic (bcc) Nd metal were synthesized at 5 GPa and 1473 K. X-ray photoelectron spectroscopy (XPS) measurements indicate that the Nd 3d peak shifts to higher energy in NdO relative to Nd2O3, suggesting the possibility of complex electronic states in NdO. Formation enthalpies for the reaction 1/3Nd2O3 + 1/3bcc Nd = NdO obtained from high temperature solution calorimetry in molten sodium molybdate and for the reaction dhcp Nd (metal) = bcc Nd (metal) from differential scanning calorimetry are 25.98 ± 8.65 and 5.2 kJ/mol, respectively. Utilizing these enthalpy values, we calculated the pressure-temperature boundary for the reaction 1/3 bcc Nd + 1/3Nd2O3 = NdO, which has a negative P-T slope of -1.68× 10-4 GPa/K. These insights reveal the high pressure behavior of NdO and neodymium metal, underscoring their potential utility in technological applications.

Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.

Importance: Targeted therapies based on underlying tumor genomic susceptible alterations have been approved for patients with metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC). Objective: To assess trends and disparities in next-generation sequencing (NGS) testing among patients with mPC and aUC. Design, Setting, and Participants: This retrospective cohort study used an electronic health record-derived database to extract deidentified data of patients receiving care from US physician practices, hospital-affiliated clinics, and academic practices. Patients diagnosed with mPC or aUC between March 1, 2015, and December 31, 2022, were included. Exposures: Social determinants of health evaluated by race and ethnicity, socioeconomic status (SES), region, insurance type, and sex (for aUC). Main Outcomes and Measures: The primary outcomes were (1) NGS testing rate by year of mPC and aUC diagnosis using Clopper-Pearson 2-sided 95% CIs and (2) time to NGS testing, which considered death as a competing risk. Cumulative incidence functions were estimated for time to NGS testing. Disparities in subdistributional incidence of NGS testing were assessed by race and ethnicity, SES, region, insurance type, and sex (for aUC) using the Fine-Gray modified Cox proportional hazards model, assuming different subdistribution baseline hazards by year of mPC and aUC diagnosis. Results: A total of 11 927 male patients with mPC (167 Asian [1.6%], 1236 Black [11.6%], 687 Hispanic or Latino [6.4%], 7037 White [66.0%], and 1535 other [14.4%] among 10 662 with known race and ethnicity) and 6490 patients with aUC (4765 male [73.4%]; 80 Asian [1.4%], 283 Black [4.8%], 257 Hispanic or Latino [4.4%], 4376 White [74.9%], and 845 other [14.5%] among 5841 with known race and ethnicity) were eligible and included. Both cohorts had a median age of 73 years (IQR, 66-80 years), and most underwent NGS testing before first-line treatment in the mPC cohort (1502 [43.0%]) and before second-line treatment in the aUC cohort (1067 [51.3%]). In the mPC cohort, the rates of NGS testing increased from 19.0% in 2015 to 27.1% in 2022, but Black patients (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84) and Hispanic or Latino patients (HR, 0.70; 95% CI, 0.60-0.82) were less likely to undergo NGS testing. Patients with mPC who had low SES (quintile 1: HR, 0.74 [95% CI, 0.66-0.83]; quintile 2: HR, 0.89 [95% CI, 0.80-0.99]), had Medicaid (HR, 0.53; 95% CI, 0.38-0.74) or Medicare or other government insurance (HR, 0.89; 95% CI, 0.82-0.98), or lived in the West (HR, 0.81; 95% CI, 0.70-0.94) also were less likely to undergo testing. In the aUC cohort, the NGS rate increased from 14.1% in 2015 to 46.6% in 2022, but Black patients (HR, 0.76; 95% CI, 0.61-0.96) and those with low SES (quintile 1: HR 0.77 [95% CI, 0.66-0.89]; quintile 2: HR, 0.87 [95% CI, 0.76-1.00]) or Medicaid (HR, 0.72; 95% CI, 0.53-0.97) or Medicare or other government insurance (HR, 0.88; 95% CI, 0.78-0.99) were less likely to undergo NGS testing. Patients with aUC living in the South were more likely to undergo testing (HR, 1.29; 95% CI, 1.12-1.49). Conclusions and Relevance: These findings suggest that although NGS tumor testing rates improved over time, the majority of patients still did not undergo testing. These data may help with understanding current disparities associated with NGS testing and improving access to standard-of-care health care services.

Protease shaving of Mycobacterium tuberculosis facilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of infectious disease death and lacks a vaccine capable of protecting adults from pulmonary TB. Studies have shown that Mtb uses a variety of mechanisms to evade host immunity. Secreted Mtb proteins such as Type VII secretion system substrates have been characterized for their ability to modulate anti-Mtb immunity; however, studies of other pathogens such as Salmonella Typhi and Staphylococcus aureus have revealed that outer membrane proteins can also interact with the innate and adaptive immune system. The Mtb outer membrane proteome has received relatively less attention due to limited techniques available to interrogate this compartment. We filled this gap by deploying protease shaving and quantitative mass spectrometry to identify Mtb outer membrane proteins which serve as nodes in the Mtb-host interaction network. These analyses revealed several novel Mtb proteins on the Mtb surface largely derived from the PE/PPE class of Mtb proteins, including PPE18, a component of a leading Mtb vaccine candidate. We next exploited the localization of PPE18 to decorate the Mtb surface with heterologous proteins and deliver these surface-engineered Mtb to the phagosome. Together, these studies reveal potential novel targets for new Mtb vaccines as well as facilitate new approaches to study difficult to study cellular compartments during infection.

Histologic Activity from Neoterminal Ileal Biopsies in Patients with Crohn's Disease in Endoscopic Remission is Associated with Postoperative Recurrence.

BACKGROUND: Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. This study aimed to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). METHODS: In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009-2020 with endoscopic biopsies of ileal mucosa from Rutgeerts' i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts' score≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors for POR, postoperative biologic prophylaxis, and histology activity was designed. RESULTS: A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group (p=0.04). After adjusting for clinical risk factors for POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; p=0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; p=0.05) were independently associated with subsequent composite POR risk. CONCLUSIONS: In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic and radiographic, recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts' i0 disease may provide a novel target to reduce disease recurrence in this population.

Reactivity of Tetrel-Functionalized Heptaphosphane Clusters toward Azides.

In this work, the reactivity of tetrel-functionalized phosphorus clusters toward organoazides is probed. Clusters (Me3Si)3P7 (1) and (Me3Ge)3P7 (2) were reacted with benzyl azide, phenyl azide, and 4-bromophenyl azide, and it was found that the [RN] (R = benzyl, phenyl, and 4-bromophenyl) unit from the azide inserted into the phosphorus-tetrel bonds on the cluster, accompanied by N2 elimination. Through control of the azide stoichiometry, the mono-, bis-, and tris-inserted products could be observed, consistent with these insertions proceeding in a stepwise manner. The bonding between the amine moieties and clusters was further investigated by computational chemistry, and the findings were consistent with the phosphorus cluster having undergone a formal oxidation. These insertion reactions are a convenient means of accessing Zintl clusters functionalized with exo-nitrogen-bonded moieties, which, to the best of our knowledge, were previously unknown.

Different relative scalings between transient forces and thermal fluctuations tune regimes of chromatin organization.

Within the nucleus, structural maintenance of chromosome protein complexes, namely condensin and cohesin, create an architecture to facilitate the organization and proper function of the genome. Condensin, in addition to performing loop extrusion, creates localized clusters of chromatin in the nucleolus through transient crosslinks. Large-scale simulations revealed three different dynamic behaviors as a function of timescale: slow crosslinking leads to no clusters, fast crosslinking produces rigid slowly changing clusters, while intermediate timescales produce flexible clusters that mediate gene interaction. By mathematically analyzing different relative scalings of the two sources of stochasticity, thermal fluctuations and the force induced by the transient crosslinks, we predict these three distinct regimes of cluster behavior. Standard time-averaging that takes the fluctuations of the transient crosslink force to zero predicts the existence of rigid clusters. Accounting for the interaction of both fluctuations from the crosslinks and thermal noise with an effective energy landscape predicts the timescale-dependent lifetimes of flexible clusters. No clusters are predicted when the fluctuations of the transient crosslink force are taken to be large relative to thermal fluctuations. This mathematical perturbation analysis illuminates the importance of accounting for stochasticity in local incoherent transient forces to predict emergent complex biological behavior.

Reusable tutorials for using cloud-based computing environments for the analysis of bacterial gene expression data from bulk RNA sequencing.

This manuscript describes the development of a resource module that is part of a learning platform named "NIGMS Sandbox for Cloud-based Learning" https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox at the beginning of this Supplement. This module delivers learning materials on RNA sequencing (RNAseq) data analysis in an interactive format that uses appropriate cloud resources for data access and analyses. Biomedical research is increasingly data-driven, and dependent upon data management and analysis methods that facilitate rigorous, robust, and reproducible research. Cloud-based computing resources provide opportunities to broaden the application of bioinformatics and data science in research. Two obstacles for researchers, particularly those at small institutions, are: (i) access to bioinformatics analysis environments tailored to their research; and (ii) training in how to use Cloud-based computing resources. We developed five reusable tutorials for bulk RNAseq data analysis to address these obstacles. Using Jupyter notebooks run on the Google Cloud Platform, the tutorials guide the user through a workflow featuring an RNAseq dataset from a study of prophage altered drug resistance in Mycobacterium chelonae. The first tutorial uses a subset of the data so users can learn analysis steps rapidly, and the second uses the entire dataset. Next, a tutorial demonstrates how to analyze the read count data to generate lists of differentially expressed genes using R/DESeq2. Additional tutorials generate read counts using the Snakemake workflow manager and Nextflow with Google Batch. All tutorials are open-source and can be used as templates for other analysis.

Benzene-1,2,4,5-tetrol.

The crystal structure of the title compound was determined at 120 K. It crystallizes in the triclinic space group P with four independent mol-ecules in the asymmetric unit. In the crystal, each symmetry-unique mol-ecule forms π-π stacks on itself, giving four unique π-π stacking inter-actions. Inter-molecular hydrogen bonding is observed between each pair of independent mol-ecules, where each hy-droxy group can act as a hydrogen-bond donor and acceptor.

Blockade of IL-1ß and PD-1 with combination chemotherapy reduces systemic myeloid suppression in metastatic pancreatic cancer with heterogeneous effects in the tumor.

Innate inflammation promotes tumor development, although the role of innate inflammatory cytokines in established human tumors is unclear. Here we report clinical and translational results from a phase Ib trial testing whether IL-1ß blockade in human pancreatic cancer would alleviate myeloid immunosuppression and reveal antitumor T-cell responses to PD-1 blockade. Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n=10) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1ß (IL-1ß), the PD-1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Analysis of paired peripheral blood from patients in the trial versus patients receiving multiagent chemotherapy showed a modest increase in HLA-DR+CD38+ activated CD8+ T cells and a decrease in circulating monocytic myeloid-derived suppressor cells (MDSCs) by flow cytometry for patients in the trial, but not in controls. Similarly, we used patient serum to differentiate monocytic MDSCs in vitro and showed that functional inhibition of T-cell proliferation was reduced when using on-treatment serum samples from patients in the trial but not when using serum from patients treated with chemotherapy alone. Within the tumor we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD-1 and IL-1ß blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

Polymerization of ZBTB transcription factors regulates chromatin occupancy.

BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.

Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.

Effectiveness of bedside staplers in bariatric robotic procedures.

BACKGROUND: Few studies have evaluated the use of laparoscopic staplers in robotic procedures (bedside stapling, BS). This study aims to evaluate the effectiveness of BS compared with robotic staplers (RS) in bariatric robotic procedures. METHODS: Patients who underwent robotic sleeve gastrectomy or gastric bypass elective procedures between 1/1/2021 and 12/31/2021 were extracted from PINC AI™ Healthcare Data. The following clinical outcomes were compared: blood transfusion, bleeding, anastomotic leak, intensive care unit (ICU) visit, and 30-day readmission, operating room (OR) time, inpatient costs, and length of stay. We evaluated baseline balance in BS and RS and bivariate association between covariates and outcomes using Chi-square or Fisher exact test and t-test or ANOVA. Multivariable general linear mixed models (GLMMs) with respective gamma or binomial distribution and log-link function were used to obtain adjusted outcomes variations between BS and RS. RESULTS: Total of 7268 discharges were included with 1603 (22.1%) BS and 5665 (77.9%) RS cases. RS cases consisted of a higher number of patients who were Hispanic (17.0% vs. 9.4%), had Medicaid (26.9% vs. 19.4%) and underwent sleeve gastrectomy (68.4% vs. 53.5%). Higher proportions of RS cases were done by providers in Northeast region (35.5% vs. 24.3%), smaller size (< 500 beds; 71.1% vs. 52.3%), and teaching hospitals (59.4% vs. 39%). The adjusted outcomes variations demonstrated that patients that had RS were significantly more likely to have blood transfusions, ICU stays, increased ORT (19 min) and costs ($1273). Sensitivity analysis showed similar results, except no significant differences in blood transfusion rates in both groups. CONCLUSIONS: Bedside staplers significantly reduce healthcare resource utilization with equivalent effectiveness and fewer ICU stays compared to robotic staplers.

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan.

For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1-7. Here we examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK-AMPK-mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.

Ingrained: Rice farming and the risk of zoonotic spillover, examples from Cambodia.

Rice cultivation in Southeast Asia is a One Health interface intersecting human, animal, and environmental health. This complexity creates a potential for zoonotic transmission between diverse reservoirs. Bats harbor viruses like Nipah; mosquitoes transmit arboviruses; rodents spread hantaviruses. Domestic animals- including pigs with influenza and dogs with rabies and aquatic animals can also transmit pathogens. Climate change and urbanization may further disrupt rice agro-ecologies. This paper explores animal viral reservoirs, vectors, and historical practices associated with risk in rice farming. Climate and land use changes could enhance spillover. Solutions are proposed, including surveillance of animals, vectors, water, and air to detect threats before major outbreaks, such as improved biosecurity, hygiene, and livestock vaccinations. Ecological viral surveillance and agricultural interventions together can reduce zoonotic transmission from rice farming.

Automated Radiosynthesis of [18F]FluoFAPI and Its Dosimetry and Single Acute Dose Toxicological Evaluation.

BACKGROUND: Cancer-associated fibroblasts have become a new target for therapy. Fibroblasts present within malignancies express the fibroblast activation protein (FAP). Inhibitors to FAP (FAPI) are small molecules recently developed as a theranostic agents for imaging and radiotherapy. All currently used FAPI rely on a linker-chelator complex attached to the 'inhibitor'. We describe a new automated method of the direct attachment of the radioisotope to the inhibitor, resulting in a >50% MW reduction with the hope of an improved tumor-to-background ratio and tumor uptake. METHODS: [18F]FluroFAPI was developed from a Sn precursor. This allowed for subsequent automated radioflourination. We obtained the biodistribution of [18F]FluroFAPI in rats, performed estimated human radiation dosimetry, and performed a 100× expected single dose toxicology analysis for eventual first-in-human experiments. RESULTS: The synthesis of the Sn precursor for FluorFAPI and the automated synthesis of [18F]FluroFAPI was demonstrated. [18F]FluroFAPI had favorable estimated human radiation dosimetry, and demonstrated no adverse effects when injected at a dose of 100× that planned for [18F]FluroFAPI. CONCLUSIONS: With the successful development of an automated synthesis of [18F]FluroFAPI, first-in-human testing can be planned with the hope of an improved tumor-to-background performance compared to other FAPI agents.

Tris-Silanide f-Block Complexes: Insights into Paramagnetic Influence on NMR Chemical Shifts.

The paramagnetism of f-block ions has been exploited in chiral shift reagents and magnetic resonance imaging, but these applications tend to focus on 1H NMR shifts as paramagnetic broadening makes less sensitive nuclei more difficult to study. Here we report a solution and solid-state (ss) 29Si NMR study of an isostructural series of locally D 3h -symmetric early f-block metal(III) tris-hypersilanide complexes, [M{Si(SiMe3)3}3(THF)2] (1-M; M = La, Ce, Pr, Nd, U); 1-M were also characterized by single crystal and powder X-ray diffraction, EPR, ATR-IR, and UV-vis-NIR spectroscopies, SQUID magnetometry, and elemental analysis. Only one SiMe3 signal was observed in the 29Si ssNMR spectra of 1-M, while two SiMe3 signals were seen in solution 29Si NMR spectra of 1-La and 1-Ce. This is attributed to dynamic averaging of the SiMe3 groups in 1-M in the solid state due to free rotation of the M-Si bonds and dissociation of THF from 1-M in solution to give the locally C 3v -symmetric complexes [M{Si(SiMe3)3}3(THF) n ] (n = 0 or 1), which show restricted rotation of M-Si bonds on the NMR time scale. Density functional theory and complete active space self-consistent field spin-orbit calculations were performed on 1-M and desolvated solution species to model paramagnetic NMR shifts. We find excellent agreement of experimental 29Si NMR data for diamagnetic 1-La, suggesting n = 1 in solution and reasonable agreement of calculated paramagnetic shifts of SiMe3 groups for 1-M (M = Pr and Nd); the NMR shifts for metal-bound 29Si nuclei could only be reproduced for diamagnetic 1-La, showing the current limitations of pNMR calculations for larger nuclei.