Exploring the Te(II)/Te(IV) Redox Couple of a Tellurorosamine Chromophore: Photophysical, Photochemical, and Electrochemical Studies.

A tellurorosamine dye [Te(II)] undergoes aerobic photooxidation. Although Te(IV) species have been used in a number of oxidations, key Te(IV)-oxo and Te(IV)-bis(hydroxy) intermediates are challenging to study. Under aerobic irradiation with visible light, Te(II) (λmax = 600 nm) transforms into a Te(IV) species (λmax = 669 nm). The resultant Te(IV) species is not stable in the dark or at -20 °C, decomposing back to Te(II) and other byproducts over many hours. To eliminate the structural ambiguity of the Te(IV) photoproduct, we used spectroelectrochemistry, wherein the bis(hydroxy) Te(IV)-(OH)2 was electrochemically generated under anaerobic conditions. The absorption of Te(IV)-(OH)2 matches that of the Te(IV) photoproduct. Because isosbestic points are maintained both photochemically and electrochemically, the oxo core formed photochemically must rapidly equilibrate with Te(IV)-(OH)2. Calculations on the bis(hydroxy) versus oxo species further corroborate that the equilibration is rapid and the spectra of the two species are similar. To further explore Te(IV) cores, two novel compounds, Te(IV)-Cl2 and Te(IV)-Br2, were synthesized. Characterization of Te(IV)-X2 was simplified because these cores have no analogue to the Te(IV)-(O)/Te(IV)-(OH)2 equilibrium. This work provides insights into the photophysical and electrochemical behavior of Te analogues of chalcogenoxanthylium dyes, which are relevant for a broad range of photochemical applications.

An Unusual Case of Lethal Strongyloides stercoralis-Associated Chronic Fulminant Colitis in an Immunocompetent Patient.

A 70-year-old immunocompetent Lebanese male presented with 3-month history of watery diarrhoea and abdominal pain after recently arriving to Australia from Lebanon. He had a colectomy for an iatrogenic bowel perforation associated with a colonoscopy in Lebanon several months prior. His computed tomography (CT) scan demonstrated pancolitis. Stool culture and polymerase chain reaction (PCR) were positive for Strongyloides stercoralis. Despite Strongyloides treatment and total parenteral nutrition, his pancolitis unexpectedly persisted despite negative stool cultures, and the patient failed to progress over several weeks with worsening abdominal pain. A colectomy was considered. However, due to his recent myocardial infarct requiring cardiac stenting, his anticoagulant and antiplatelets could not be ceased for at least 3 months without significant cardiac risk. After hospitalisation for several weeks in Australia, he was discharged against medical advice and flew back to Lebanon, where he presented with worsening pain and underwent a subtotal colectomy. Unfortunately, he developed multiorgan failure and died 3 weeks following his colectomy. Strongyloides-related pancolitis is a rare condition in immunocompetent adults that has the potential to persist and be lethal, despite microbiological antiparasitic eradication.

Vision-related quality of life after unilateral occipital stroke.

BACKGROUND/OBJECTIVES: Stroke damage to the primary visual cortex induces large, homonymous visual field defects that impair daily living. Here, we asked if vision-related quality of life (VR-QoL) is impacted by time since stroke. SUBJECTS/METHODS: We conducted a retrospective meta-analysis of 95 occipital stroke patients (female/male = 26/69, 27-78 years old, 0.5-373.5 months poststroke) in whom VR-QoL was estimated using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ) and its 10-item neuro-ophthalmic supplement (Neuro10). Visual deficit severity was represented by the perimetric mean deviation (PMD) calculated from 24-2 Humphrey visual fields. Data were compared with published cohorts of visually intact controls. The relationship between VR-QoL and time poststroke was assessed across participants, adjusting for deficit severity and age with a multiple linear regression analysis. RESULTS: Occipital stroke patients had significantly lower NEI-VFQ and Neuro10 composite scores than controls. All subscale scores describing specific aspects of visual ability and functioning were impaired except for ocular pain and general health, which did not differ significantly from controls. Surprisingly, visual deficit severity was not correlated with either composite score, both of which increased with time poststroke, even when adjusting for PMD and age. CONCLUSIONS: VR-QoL appears to improve with time postoccipital stroke, irrespective of visual deficit size or patient age at insult. This may reflect the natural development of compensatory strategies and lifestyle adjustments. Thus, future studies examining the impact of rehabilitation on daily living in this patient population should consider the possibility that their VR-QoL may change gradually over time, even without therapeutic intervention.

Plant synthetic biology as a tool to help eliminate hidden hunger.

Agricultural systems are under increasing pressure from declining environmental conditions, a growing population, and changes in consumer preferences, resulting in widespread malnutrition-related illnesses. Improving plant nutritional content through biotechnology techniques such as synthetic biology is a promising strategy to help combat hidden hunger caused by the lack of affordable and healthy foods in human diets. Production of compounds usually found in animal-rich diets, such as vitamin D or omega-3 fatty acids, has been recently demonstrated in planta. Here, we review recent biotechnological approaches to biofortifying plants with vitamins, minerals, and other metabolites, and summarise synthetic biology advances that offer the opportunity to build on these early biofortification efforts.

Extracellular Vesicle ASC: A Novel Mediator for Lung-Brain Axis in Preterm Brain Injury.

Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI) are among the most common morbidities affecting preterm infants. Although BPD is a predictor of poor NDI, it is currently uncertain how BPD contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are involved in inter-organ communication in diverse pathological processes. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly and activation of inflammatory response. We assessed expression profiles of alveolar macrophage (AM) markers, CD11b, CD11c, and CD206, and ASC in EVs isolated from the plasma of preterm infants at risk for BPD at 1 week of age. We found that infants on higher fraction inspired oxygen (FiO2) therapy (HO2, ≥30%) had increased levels of AM-derived EV-ASC compared with infants on lower FiO2 (LO2, <30%). To assess the function of these EVs, we performed adoptive transfer experiments by injecting them into the circulation of newborn mice. We discovered that mice that received EVs from infants on HO2 had increased lung inflammation, decreased alveolarization, and disrupted vascular development, the hallmarks of BPD. Importantly, these EVs crossed the blood-brain barrier and the EVs from infants on HO2 caused inflammation, reduced cell survival, and increased cell death with features of pyroptosis and necroptosis in the hippocampus. These results highlight a novel role for AM-derived EV-ASC in mediating the lung-to-brain crosstalk that is critical in the pathogenesis of BPD and brain injury and identify potential novel targets for preventing and treating BPD and brain injury in preterm infants.

Tension directs cancer cell migration over fiber alignment through energy minimization.

Cell migration during many fundamental biological processes including metastasis requires cells to traverse tissue with heterogeneous mechanical cues that direct migration as well as determine force and energy requirements for motility. However, the influence of discrete structural and mechanical cues on migration remains challenging to determine as they are often coupled. Here, we decouple the pro-invasive cues of collagen fiber alignment and tension to study their individual impact on migration. When presented with both cues, cells preferentially travel in the axis of tension against fiber alignment. Computational and experimental data show applying tension perpendicular to alignment increases potential energy stored within collagen fibers, lowering requirements for cell-induced matrix deformation and energy usage during migration compared to motility in the direction of fiber alignment. Energy minimization directs migration trajectory, and tension can facilitate migration against fiber alignment. These findings provide a conceptual understanding of bioenergetics during migration through a fibrous matrix.

Molecular Ball Joints: Mechanochemical Perturbation of Bullvalene Hardy-Cope Rearrangements in Polymer Networks.

The solution-state fluxional behavior of bullvalene has fascinated physical organic and supramolecular chemists alike. Little effort, however, has been put into investigating bullvalene applications in bulk, partially due to difficulties in characterizing such dynamic systems. To address this knowledge gap, we herein probe whether bullvalene Hardy-Cope rearrangements can be mechanically perturbed in bulk polymer networks. We use dynamic mechanical analysis to demonstrate that the activation barrier to the glass transition process is significantly elevated for bullvalene-containing materials relative to "static" control networks. Furthermore, bullvalene rearrangements can be mechanically perturbed at low temperatures in the glassy region; such behavior facilitates energy dissipation (i.e., increased hysteresis energy) and polymer chain alignment to stiffen the material (i.e., increased Young's modulus) under load. Computational simulations corroborate our work that showcases bullvalene as a reversible "low-force" covalent mechanophore in the modulation of viscoelastic behavior.

Unexpected Low Rate of Amyloid-ß Pathology in Multiple Sclerosis Patients.

The life expectancy of people with multiple sclerosis (MS) has increased, yet we have noted that development of a typical Alzheimer disease dementia syndrome is uncommon. We hypothesized that Alzheimer disease pathology is uncommon in MS patients. In 100 MS patients, the rate of amyloid-ß plasma biomarker positivity was approximately half the rate in 300 non-MS controls matched on age, sex, apolipoprotein E proteotype, and cognitive status. Interestingly, most MS patients who did have amyloid-ß pathology had features atypical for MS at diagnosis. These results support that MS is associated with reduced Alzheimer disease risk, and suggest new avenues of research. ANN NEUROL 2024.

Evaluation of the Immune Response within the Tumor Microenvironment in African American and non-Hispanic White Non-Small Cell Lung Cancer Patients.

BACKGROUND: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer (NSCLC) based on PD-L1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance. METHODS: Using a cohort of 280 NSCLC patients from the INHALE study (non-Hispanic White: n=155; African American: n=125), we evaluated PD-L1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes. RESULTS: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PD-L1 positive samples suggest these tumors contained greater numbers of γδ T-cells and resting dendritic cells, along with fewer CD8+ T-cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B-cell/plasma cell related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans. CONCLUSIONS: In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PD-L1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications. IMPACT: Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.

Trafficking of mitochondrial double-stranded RNA from mitochondria to the cytosol.

In addition to mitochondrial DNA, mitochondrial double-stranded RNA (mtdsRNA) is exported from mitochondria. However, specific channels for RNA transport have not been demonstrated. Here, we begin to characterize channel candidates for mtdsRNA export from the mitochondrial matrix to the cytosol. Down-regulation of SUV3 resulted in the accumulation of mtdsRNAs in the matrix, whereas down-regulation of PNPase resulted in the export of mtdsRNAs to the cytosol. Targeting experiments show that PNPase functions in both the intermembrane space and matrix. Strand-specific sequencing of the double-stranded RNA confirms the mitochondrial origin. Inhibiting or down-regulating outer membrane proteins VDAC1/2 and BAK/BAX or inner membrane proteins PHB1/2 strongly attenuated the export of mtdsRNAs to the cytosol. The cytosolic mtdsRNAs subsequently localized to large granules containing the stress protein TIA-1 and activated the type 1 interferon stress response pathway. Abundant mtdsRNAs were detected in a subset of non-small-cell lung cancer cell lines that were glycolytic, indicating relevance in cancer biology. Thus, we propose that mtdsRNA is a new damage-associated molecular pattern that is exported from mitochondria in a regulated manner.

NHS-Reimbursed Cannabis Flowers for Cancer Palliative Care and the Management of Chemotherapy-Induced Nausea and Vomiting: An Autobiographical Case Report.

Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of cancer treatment, affecting many patients. Cannabinoid agonists, such as nabilone and Δ9-tetrahydrocannabinol (THC), the main psychoactive component of Cannabis sativa L., have shown efficacy as antiemetics. Here, we report the case of Michael Roberts (MR), who we believe is the first British patient reimbursed by the National Health Service (NHS) England for the cost of medicinal cannabis flowers to manage CINV. Medical data were obtained from NHS records and individual funding request (IFR) forms. Patient-reported outcome measures (PROMs) were collected using validated questionnaires as part of the standard of care at the specialized private clinics where the prescription of medicinal cannabis was initiated. The patient presented with rectosigmoid adenocarcinoma with lung metastases. He received FOLFIRI (folinic acid, fluorouracil, and irinotecan) chemotherapy and underwent an emergency Hartmann's procedure with subsequent second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy and lung ablation. MR reported severe nausea and vomiting associated with the initial FOLFIRI treatment. Antiemetics metoclopramide and aprepitant demonstrated moderated efficacy. Antiemetics ondansetron, levomepromazine, and nabilone were associated with intolerable side effects. Inhalation of THC-predominant cannabis flowers in association with standard medication improved CINV, anxiety, sleep quality, appetite, overall mood, and quality of life. Our results add to the available evidence suggesting that medicinal cannabis flowers may offer valuable support in cancer palliative care integrated with standard-of-care oncology treatment. The successful individual funding request in this case demonstrates a pathway for other patients to gain access to these treatments, advocating for broader awareness and integration of cannabis-based medicinal products in national healthcare services.

VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.

Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function. We establish a method to monitor cleavage of linkages within complex Ub chains and unveil ATXN3 and MINDY as debranching enzymes. We engineer a K48-K63 branch-specific nanobody and reveal the molecular basis of its specificity in crystal structures of nanobody-branched Ub chain complexes. Using this nanobody, we detect increased K48-K63-Ub branching following valosin-containing protein (VCP)/p97 inhibition and after DNA damage. Together with our discovery that multiple VCP/p97-associated proteins bind to or debranch K48-K63-linked Ub, these results suggest a function for K48-K63-branched chains in VCP/p97-related processes.

RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene lowering a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNA SOD1 extended survival in SOD1-G93A ALS mice, surpassing survival previously seen in these mice by ASO modalities, slowed disease progression, and prevented ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.

Mutual antagonism between CD44 and integrins in glioblastoma cell traction and migration.

Cell migration is the major driver of invasion and metastasis during cancer progression. For cells to migrate, they utilize the actin-myosin cytoskeleton and adhesion molecules, such as integrins and CD44, to generate traction forces in their environment. CD44 primarily binds to hyaluronic acid (HA) and integrins primarily bind to extracellular matrix (ECM) proteins such as collagen. However, the role of CD44 under integrin-mediated conditions and vice versa is not well known. Here, we performed traction force microscopy (TFM) on U251 cells seeded on collagen I-coated polyacrylamide gels to assess the functional mechanical relationship between integrins and CD44. Performing TFM on integrin-mediated adhesion conditions, i.e., collagen, we found that CD44KO U251 cells exerted more traction force than wild-type (WT) U251 cells. Furthermore, untreated WT and CD44-blocked WT exhibited comparable results. Conversely, in CD44-mediated adhesive conditions, integrin-blocked WT cells exerted a higher traction force than untreated WT cells. Our data suggest that CD44 and integrins have a mutually antagonistic relationship where one receptor represses the other's ability to generate traction force on its cognate substrate.

When Does Primary Prevention Encroach on Secondary Prevention?

PURPOSE OF REVIEW: The risk of incident atherosclerotic cardiovascular disease (ASCVD) in primary prevention is typically lower than in secondary prevention. However, there is a spectrum of risk among individuals undergoing primary prevention with the risk in some individuals approaching those of secondary prevention. We review the clinical conditions wherein the risk in primary prevention is similar to that observed in secondary prevention. RECENT FINDINGS: Among individuals without established ASCVD, coronary artery calcium (CAC) scores ≥ 300 AU are associated with ASCVD event rates similar to secondary prevention populations. CAC score ≥ 1,000 AU are associated with an ASCVD risk seen in very high-risk secondary prevention populations. Interpretation of these observations must however consider differences in the risk reduction strategies. Current guidelines dichotomize ASCVD prevention into primary and secondary prevention, but certain primary prevention patients have an ASCVD risk equivalent to that of secondary prevention populations. Identifying higher risk primary prevention populations will allow for better risk mitigation strategies.

Development of Chronic Pain Conditions Among Women in the Military Health System.

Importance: The incidence of chronic pain has been increasing over the last decades and may be associated with the stress of deployment in active-duty servicewomen (ADSW) as well as women civilian dependents whose spouse or partner served on active duty. Objective: To assess incidence of chronic pain among active-duty servicewomen and women civilian dependents with service during 2006 to 2013 compared with incidence among like individuals at a time of reduced combat exposure and deployment intensity (2014-2020). Design, Setting, and Participants: This cohort study used claims data from the Military Health System data repository to identify ADSW and dependents who were diagnosed with chronic pain. The incidence of chronic pain among individuals associated with service during 2006 to 2013 was compared with 2014 to 2020 incidence. Data were analyzed from September 2023 to April 2024. Main Outcomes and Measures: The primary outcome was the diagnosis of chronic pain. Multivariable logistic regression analyses were used to adjust for confounding, and secondary analyses were performed to account for interactions between time period and proxies for socioeconomic status and combat exposure. Results: A total of 3 473 401 individuals (median [IQR] age, 29.0 [22.0-46.0] years) were included, with 644 478 ADSW (18.6%). Compared with ADSW in 2014 to 2020, ADSW in 2006 to 2013 had significantly increased odds of chronic pain (odds ratio [OR], 1.53; 95% CI, 1.48-1.58). The odds of chronic pain among dependents in 2006 to 2013 was also significantly higher compared with dependents from 2014 to 2020 (OR, 1.96; 95% CI, 1.93-1.99). The proxy for socioeconomic status was significantly associated with an increased odds of chronic pain (2006-2013 junior enlisted ADSWs: OR, 1.95; 95% CI, 1.83-2.09; 2006-2013 junior enlisted dependents: OR, 3.05; 95% CI, 2.87-3.25). Conclusions and Relevance: This cohort study found significant increases in the diagnosis of chronic pain among ADSW and civilian dependents affiliated with the military during a period of heightened deployment intensity (2006-2013). The effects of disparate support structures, coping strategies, stress regulation, and exposure to military sexual trauma may apply to both women veterans and civilian dependents.

Cost-effectiveness of patch testing allergens within the same group - a computational approach to optimize formaldehyde-related allergen selection.

BACKGROUND: Patch testing to multiple cross reactive allergens for allergic contact dermatitis (ACD) may not be necessary due to copositivity. OBJECTIVE: We evaluated the formaldehyde group allergens to determine the optimal, most cost-effective allergens to test. METHODS: A retrospective analysis of Mayo Clinic (1997-2022) examined the well-established copositive formaldehyde group: Formaldehyde, Quaternium 15, Hexahydro-1,3,5-tris(2-hydroxyethyl)triazine, Diazolidinyl urea, Imidazolidinyl urea, Toluenesulphonamide formaldehyde resin, DMDM hydantoin, and Ethyleneurea melamine formaldehyde mix. Patch Optimization Platform (POP) identified which single formaldehyde-related allergen optimally captures patients with clinically relevant ACD. Next, POP determined the optimal additional 1, 2, 3, etc. allergens. Cost per patch test was $5.19 (Medicare 2022). RESULTS: 9832 patients were tested to all listed allergens, with 830 having positive patch tests. POP determined that Quaternium 15 alone captures 53% of patients with ACD to the formaldehyde group; adding the optimal second allergen (Formaldehyde 1%) captures 78%; the optimal five top allergens capture over 94% of patients. The incremental cost-per-additional-diagnosis increased up to 44-fold as the number of allergens tested increased. LIMITATIONS: Data is from a single institution, and the cost-per-test was fixed to Medicare Part B in 2022. CONCLUSIONS: For diagnosing ACD, we recommend considering an optimized allergen selection algorithm.

In Response to Representativeness of U.S. News & World Report Outcome and Volume Measures for Otolaryngology.

Although outcomes account for 45% of the total ranking score in otolaryngology in the 2023-2024 U.S. News Best Hospitals rankings, little attention has been paid to the representativeness of their outcomes or volume analyses. Through retrospective review of finance data from an academic otolaryngology department, we found the overall 2023-2024 USNWR volume estimate accounted for only 10.0% (n = 2, usw 024/20,334) of all adult admissions and outpatient procedures and did not adequately represent the overall case mix or caseload.

Measurable Residual Disease and Clinical Outcomes in Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development. Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment. Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023. Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded. Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted. Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model. Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

Precise tactile localization on the human fingernail.

Fingernails are specialized features of the primate hand, which are believed to contribute to manual dexterity. The sensorimotor functions of fingernails, however, remain poorly understood. This study investigates the ability of humans to precisely localize touches applied to the fingernail plate. Nine different locations on the fingernail were touched and participants judged the location by clicking a mouse cursor on a photograph of their finger. Performance in this condition was compared with stimuli applied to the skin of the fingertip. The results showed that participants are able to localize touch on the fingernails at substantially higher than chance levels. Moreover, the precision of this ability is not appreciably lower than that of the fingertips. These results show that the fingernail is a highly sensitive sensory organ, which is capable of providing rich spatial information about tactile stimuli.