Parametrically excited shape distortion of a submillimeter bubble.

The existence of finite amplitude shape distortion caused by parametrically excited surface instabilities for a gas bubble in water driven by a temporally periodic, spatially uniform pressure field in an axisymmetric geometry is investigated. Employing a nonlinear coupled system of equations which includes shape mode interactions to third order, the resultant spherical oscillations, translation, and shape distortion of the bubble are modelled, placing no restriction on the size of the spherical oscillations. The model accounts for viscous and thermal damping with compressibility effects. The existence of synchronous and higher order parametrically induced sustained, finite amplitude, periodic shape deformation is demonstrated. The excitement of an odd shape mode via the synchronous mechanism is shown to give rise to linear bubble self-propulsion. For larger driving amplitudes, it is shown that more than one shape mode can be parametrically excited at the same driving frequency but by different resonance mechanisms, leading to more involved shape deformation and the increased possibility of bubble self-propulsion.

Exposure to blue light reduces antimicrobial resistant Pseudomonas aeruginosa isolated from dog ear infections.

Introduction: Pseudomonas aeruginosa is a leading cause of canine otitis externa. Enrofloxacin is often applied topically to treat this condition, although recalcitrant and recurring infections are common. There is evidence that exposure to blue light (400-470 nm) has a bactericidal effect on P. aeruginosa and other microorganisms. Methods: In the present study, we tested the biocidal effect of blue light (375-450 nm), alone or in combination with enrofloxacin, against six isolates of P. aeruginosa from dogs with otitis externa (5 of which were resistant to enrofloxacin). Results: Treatment of planktonic cell cultures with blue light resulted in significant (p < 0.5) reductions in Colony Forming Units (CFU) for all seven strains tested, in some cases below the limit of detection. The greatest bactericidal effect was observed following exposure to light at 405 nm wavelength (p < 0.05). Exposure to blue light for 20 min usually resulted in a greater reduction in Pseudomonas aeruginosa than enrofloxacin treatment, and combination treatment typically resulted in the largest reductions in CFU. Analysis of the genome sequences of these strains established that enrofloxacin resistance was likely the result of a S466F substitution in GyrB. However, there was no clear association between genotype and susceptibility to blue light treatment. Discussion: These results suggest that blue light treatment, particularly at 405 nm wavelength, and especially in combination with enrofloxacin therapy, could be an effective treatment for otherwise recalcitrant canine otitis externa caused by Pseudomonas aeruginosa. It may also provide a way of extending the usefulness of enrofloxacin therapy which would otherwise be ineffective as a sole therapeutic agent.

Self-propulsion of a periodically forced shape-deforming submillimeter gas bubble.

The self-propulsion (translational instability) of a gas bubble in a liquid undergoing parametrically induced axisymmetric shape distortion due to being forced by a temporally sinusoidal, spatially constant acoustic field is investigated. Employing a model which accounts for the nonlinear coupling between the spherical oscillations, the axial translation and shape deformation of the bubble, the parametric excitement of two neighboring shape modes by the fundamental resonance, at the same driving frequency is studied. It is shown that provided pertinent driving pressure threshold values are exceeded, the respective shape modes are excited on different timescales. The growth of the shape mode on the faster timescale saturates giving rise to sustained constant amplitude oscillations, while the growth of the shape mode on the slower timescale is both modulated and unbounded. During the growth of the second shape mode, growing, oscillatory bubble translation is also observed.

Immunogenicity phase II study evaluating booster capacity of nonadjuvanted AKS-452 SARS-Cov-2 RBD Fc vaccine.

AKS-452, a subunit vaccine comprising an Fc fusion of the ancestral wild-type (WT) SARS-CoV-2 virus spike protein receptor binding domain (SP/RBD), was evaluated without adjuvant in a single cohort, non-randomized, open-labelled phase II study (NCT05124483) at a single site in The Netherlands for safety and immunogenicity. A single 90 µg subcutaneous booster dose of AKS-452 was administered to 71 adults previously primed with a registered mRNA- or adenovirus-based vaccine and evaluated for 273 days. All AEs were mild and no SAEs were attributable to AKS-452. While all subjects showed pre-existing SP/RBD binding and ACE2-inhibitory IgG titers, 60-68% responded to AKS-452 via ≥2-fold increase from days 28 to 90 and progressively decreased back to baseline by day 180 (days 28 and 90 mean fold-increases, 14.7 ± 6.3 and 8.0 ± 2.2). Similar response kinetics against RBD mutant proteins (including omicrons) were observed but with slightly reduced titers relative to WT. There was an expected strong inverse correlation between day-0 titers and the fold-increase in titers at day 28. AKS-452 enhanced neutralization potency against live virus, consistent with IgG titers. Nucleocapsid protein (Np) titers suggested infection occurred in 66% (46 of 70) of subjects, in which only 20 reported mild symptomatic COVID-19. These favorable safety and immunogenicity profiles support booster evaluation in a planned phase III universal booster study of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.

Pseudomonas spp. in Canine Otitis Externa.

Canine otitis externa (OE) is a commonly diagnosed condition seen in veterinary practice worldwide. In this review, we discuss the mechanisms of the disease, with a particular focus on the biological characteristics of Pseudomonas aeruginosa and the impact that antibiotic resistance has on successful recovery from OE. We also consider potential alternatives to antimicrobial chemotherapy for the treatment of recalcitrant infections. P. aeruginosa is not a typical constituent of the canine ear microbiota, but is frequently isolated from cases of chronic OE, and the nature of this pathogen often makes treatment difficult. Biofilm formation is identified in 40-95% of P. aeruginosa from cases of OE and intrinsic and acquired antibiotic resistance, especially resistance to clinically important antibiotics, highlights the need for alternative treatments. The role of other virulence factors in OE remains relatively unexplored and further work is needed. The studies described in this work highlight several potential alternative treatments, including the use of bacteriophages. This review provides a summary of the aetiology of OE with particular reference to the dysbiosis that leads to colonisation by P. aeruginosa and highlights the need for novel treatments for the future management of P. aeruginosa otitis.

Testing of a custom, portable drill press to minimize probe misalignment in sap flow sensors.

The accurate estimation of plant transpiration is critical to the fields of hydrology, plant physiology and ecology. Among the various methods of measuring transpiration in the field, the sap flow methods based on head pulses offers a cost-effective and energy-efficient option to directly measure the plant-level movement of water through the hydraulically active tissue. While authors have identified several possible sources of error in these measurements, one of the most common sources is misalignment of the sap flow probes due to user error. Though the effects of probe misalignment are well documented, no device or technique has been universally adopted to ensure the proper installation of sap flow probes. In this paper we compare the magnitude of misalignment errors among a 5 mm thick drilling template (DT), a 10 mm thick DT, and a custom designed, field-portable drill press. The different techniques were evaluated in the laboratory using a 7.5 cm wood block and in the field, comparing differences in measured sap flow. Based on analysis of holes drilled in the wood block, we found that the portable drill press was most effective in assuring that drill holes remained parallel, even at 7.5 cm depth. In field installations, nearly 50% of holes drilled with a 5 mm template needed to be redrilled while none needed to be when drilled with the drill press. Widespread use of a portable drill press when implementing the heat pulse method would minimize alignment uncertainty and allow a clearer understanding of other sources of uncertainty due to variability in tree species, age, or external drivers or transpiration.

Analyzing the impact of agricultural BMPs on stream nutrient load and biotic health in the Susquehanna-Chemung basin of New York.

Despite the widespread use of agricultural best management practices (BMPs) to reduce watershed scale nutrient loads, there remain few studies that use directly observed data - instead of models - to evaluate BMP effectiveness at the watershed scale. In this study, we make use of extensive ambient water quality data, stream biotic health data, and BMP implementation data within the New York State portion of the Chesapeake Bay watershed to assess the role of BMPs on reducing nutrient loads and modifying biotic health in major rivers. The specific BMPs considered were riparian buffers and nutrient management planning. A simple mass balance approach was used to evaluate the role of wastewater treatment plant nutrient reductions, agricultural land use changes, and these two agricultural BMPs in matching observed downward trends in nutrient load. In the Eastern nontidal network (NTN) catchment - where BMPs have been more widely reported - the mass balance model suggested a small but discernible contribution of BMPs in matching the observed downward trend in total phosphorus. Contrastingly, BMP implementations did not show clear contributions towards total nitrogen reductions in the Eastern NTN catchment nor for the total nitrogen and phosphorus in the Western NTN catchment, where BMP implementation data are more limited. Assessment of the relationship between stream biotic health and BMP implementation using regression models found limited connection between extent of BMP implementation and biotic health. In this case, however, spatiotemporal mismatches between the datasets and the relatively stable biotic health, typically of moderate to good quality even before BMP implementation, may reflect the need for better monitoring design to assess BMP effects at the subwatershed scale. Additional studies, perhaps using citizen scientists, may be able to provide more suitable data within the existing frameworks of the long-term surveys. Given the preponderance of studies that rely only on modeling to understand nutrient loading reductions achieved by implementation of BMPs, it is essential to continue to collect empirical data to meaningfully evaluate whether there are actual measurable changes due to BMPs.

A low cost, low power sap flux device for distributed and intensive monitoring of tree transpiration.

Accurate estimation of transpiration in individual trees is important for understanding plant responses to environmental drivers, closing the water balance in forest stands and catchments, and calibrating earth system models, among other applications. However, the cost and power consumption of commercial systems based on sap flow methods still limit their usage. We developed and tested a cost-effective (<$150), simple to construct, and energy efficient sap flux device based on the heat pulse method. Energy savings were achieved by reducing the voltage of heat pulses and using an internal clock to completely shut down the device between pulses. Device accuracy was confirmed by laboratory estimates of sap flow made on excised branches of Acer saccharum and Tsuga canadensis (adjusted R2 = 0.96). In a 174-d field installation of 12 devices, batteries (eight rechargeable Ni-MH AA) needed to be replaced every 14 days. Sap flux measurements in the field tracked expected variations in vapor pressure deficit and tree phenology. The low cost, compact design, reliability, and power consumption of this device enable sap flux studies to operate with more replication and in more diverse ecological settings than has been practical in the past.

BL-8040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed/refractory acute myelogenous leukemia: An open-label safety and efficacy phase 2a study.

BACKGROUND: CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high-affinity CXCR4 antagonist BL-8040 with high-dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML. METHODS: Forty-two patients received treatment with BL-8040 monotherapy for 2 days followed by a combination of BL-8040 with HiDAC for 5 days. Six escalating BL-8040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg/kg), and 1.5 mg/kg was selected as the dose for the expansion phase (n = 23). RESULTS: BL-8040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL-8040 doses ≥1.0 mg/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5-mg/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5-mg/kg phase, and 21.8 months for responding patients in the 1.5-mg/kg cohort. Two days of BL-8040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold-changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts. CONCLUSIONS: The current results demonstrate the efficacy of CXCR4 targeting with BL-8040 and support continued clinical development in acute myelogenous leukemia.

BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial.

Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC (NCT02826486). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8+ effector T cell tumor infiltration, decreased myeloid-derived suppressor cells (MDSCs) and further decreased circulating regulatory T cells. In cohort 2, 22 patients received BL-8040 and pembrolizumab with chemotherapy, with an ORR, DCR and median duration of response of 32%, 77% and 7.8 months, respectively. These data suggest that combined CXCR4 and PD-1 blockade may expand the benefit of chemotherapy in PDAC and warrants confirmation in subsequent randomized trials.

Behavioural Differences in Dogs with Atopic Dermatitis Suggest Stress Could Be a Significant Problem Associated with Chronic Pruritus.

Canine atopic dermatitis (cAD) is a common allergic skin condition in dogs that causes chronic pruritus. The overall quality of life in dogs with cAD is known to be reduced, and human patients with pruritic conditions report significant psychological burdens from pruritus-induced stress, and atopic dermatitis is associated with significant psychopathological morbidities. We tested the hypothesis that dogs with cAD would display more problem behaviours that could be indicative of stress than would healthy controls. Behavioural data were gathered directly from owners using a validated dog behaviour questionnaire for 343 dogs with a diagnosis of cAD and 552 healthy controls, and scores were also provided for their dog's pruritus severity. Regression modelling, controlling for potential confounding variables (age, sex, breed, neuter status or other health problem(s)) showed for the first time that pruritus severity in dogs with cAD was associated with increased frequency of behaviours often considered problematic, such as mounting, chewing, hyperactivity, coprophagia, begging for and stealing food, attention-seeking, excitability, excessive grooming, and reduced trainability. Whilst causality cannot be ascertained from this study, the behaviours that were associated with pruritus severity are redirected, self/environment-directed displacement behaviours, which are often considered indicative of stress. Further investigation is warranted, and stress reduction could be helpful when treating dogs with cAD.

Environmental risk factors for canine atopic dermatitis: a retrospective large-scale study in Labrador and golden retrievers.

BACKGROUND: Canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterized by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors. OBJECTIVES: To evaluate associations between environmental factors and case-control status in two closely related, at-risk breeds, the Labrador retriever and golden retriever. ANIMALS: Two thousand four hundred and forty-five pet dogs, of which 793 were classed as cases (575 Labrador and 218 golden retrievers) and 1,652 as controls (1,120 Labrador and 532 golden retrievers). METHODS AND MATERIALS: Case-control status was assigned based upon owner response to a standardized validated questionnaire. Retrospective data on rearing environment were collected via additional questions. Univariate and multivariate logistic regressions were utilized to evaluate associations between environmental factors and case-control status. RESULTS: Risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labrador retrievers, chocolate-coloured dogs were at greater risk of having cAD than black- or yellow-coated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: This study is the largest of its kind to date to investigate the role of the environment in cAD. Although precise triggers are unclear, this study complements earlier studies in highlighting the protective role of a rural environment and some novel associations with disease development.

AGI-134: a fully synthetic α-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models.

BACKGROUND: Treatments that generate T cell-mediated immunity to a patient's unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galα1-3Galß1-4GlcNAc (α-Gal) in situ leading to opsonization with pre-existing natural anti-α-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity. METHODS: Various immunological effects of coating tumor cells with α-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (α1,3GT-/-) mice. CDC and phagocytosis data were analyzed by one-way ANOVA, ADCC results by paired t-test, distal tumor growth by Mantel-Cox test, C5a data by Mann-Whitney test, and single tumor regression by repeated measures analysis. RESULTS: In vitro, α-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8α+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in α1,3GT-/- mice, intratumoral AGI-134 administration leads to primary tumor regression and has a robust abscopal effect, i.e., it protects from the development of distal, uninjected lesions. Combinations of AGI-134 and anti-PD-1 antibody shows a synergistic benefit in protection from secondary tumor growth. CONCLUSIONS: We have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment.

Landscape Features Associated With Blacklegged Tick (Acari: Ixodidae) Density and Tick-Borne Pathogen Prevalence at Multiple Spatial Scales in Central New York State.

Blacklegged ticks (Ixodes scapularis Say, Acari: Ixodidae) are the most commonly encountered and medically relevant tick species in New York State (NY) and have exhibited recent geographic range expansion. Forests and adjacent habitat are important determinants of I. scapularis density and may influence tick-borne pathogen prevalence. We examined how percent forest cover, dominant land cover type, and habitat type influenced I. scapularis nymph and adult density, and associated tick-borne pathogen prevalence, in an inland Lyme-emergent region of NY. I. scapularis nymphs and adults were collected from edge and wooded habitats using tick drags at 16 sites in Onondaga County, NY in 2015 and 2016. A subsample of ticks from each site was tested for the presence of Borrelia burgdorferi, Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia microti using a novel multiplex real-time polymerase chain reaction (PCR) assay, and deer tick virus using reverse transcription-PCR. Habitat type (wooded versus edge) was an important determinant of tick density; however, percent forest cover had little effect. B. burgdorferi was the most commonly detected pathogen and was present in ticks from all sites. Ba. microti and deer tick virus were not detected. Habitat type and dominant land cover type were not significantly related to B. burgdorferi presence or prevalence; however, ticks infected with A. phagocytophilum and B. miyamotoi were collected more often in urban environments. Similarity between B. burgdorferi prevalence in Onondaga County and hyperendemic areas of southeastern NY indicates a more rapid emergence than expected in a relatively naive region. Possible mechanistic processes underlying these observations are discussed.

Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness.

BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle. A thorough analysis of skeletal muscle tissue was undertaken in order to identify defects in muscle development caused by the lack of SLK. Isometric force analysis was performed on adult knockout mice and compared to age-matched wild-type mice. Furthermore, cardiotoxin injections were performed followed by immunohistochemistry for myogenic markers to assess the efficiency muscle regeneration following SLK deletion. RESULTS: We show here that early deletion of SLK from the myogenic lineage does not markedly impair skeletal muscle development but delays the regenerative process. Interestingly, adult mice (~6 months) display an increase in the proportion of central nuclei and increased p38 activation. Furthermore, mice as young as 3 months old present with decreased force generation, suggesting that the loss of SLK impairs myofiber stability and function. Assessment of structural components revealed aberrant localization of focal adhesion proteins, such as FAK and paxillin. Our data show that the loss of SLK results in unstable myofibers resulting in a progressive myopathy. Additionally, the loss of SLK resulted in a delay in muscle regeneration following cardiotoxin injections. CONCLUSIONS: Our results show that SLK is dispensable for muscle development and regeneration but is required for myofiber stability and optimal force generation.

Microscopical characterization of known postmortem root bands using light and scanning electron microscopy.

A postmortem root band (PMRB) is a distinct microscopic feature that is postulated to occur in hair remaining in the follicle during the postmortem interval [1] (Petraco et al., 1998). The scientific validity of this premise has been highlighted in two recent high-profile criminal cases involving PMRBs [2,3] (State of Florida v. Casey Marie Anthony, 2008; People v. Kogut, 2005). To better understand the fundamental aspects of postmortem root banding, the microscopical properties of known PMRBs1 were characterized by light microscopy, and scanning electron microscope (SEM) imaging of microtomed sections of hairs showing root banding. The results from this study show that the appearance of the PMRB may be due to the degradation of the chemically labile, non-keratin intermacrofibrillar matrix (IMM) in the pre-keratin/keratogenous region of anagen hairs. In addition, this degradation is confined to the cortex of the hair, with no apparent damage to the layers of the cuticle. These results could provide valuable information for determining the mechanism of band formation, as well as identify a set of microscopic features that could be used to distinguish hairs with known PMRBs from similarly looking environmentally degraded hairs.

Chloride sources in urban and rural headwater catchments, central New York.

Road salt used as a deicing agent in winter months has become an emerging contaminant to streams and groundwater. In central New York, road salts are applied heavily during winter months. Recognizing potential sources of salinity to a river may reveal processes controlling the salinization of freshwater systems, with implications for future management practices. The Tioughnioga River, located in central New York, is a headwater of the Susquehanna River, which flows into the Chesapeake Bay. Salinity of the Tioughnioga River water has been increasing since the late 1930s. In this study, water samples were collected weekly at the East and West Branches of the Tioughnioga River from 2012 to 2014. We characterize natural and anthropogenic sources of salinity in the Tioughnioga River, using two independent approaches: (1) chloride to bromide ratios (Cl/Br) and (2) linear discriminant analysis. Ratios of Cl/Br suggest that road salt runoff influence is notable in both branches, but is more significant in the West Branch, consistent with a greater area of urban land. Linear discriminant analysis confirms the results of Cl/Br in the West Branch and further indicates presence of Appalachian Basin Brines in the East Branch, although their contribution may be volumetrically small. Longitudinal stream Cl concentration profiles indicate that sources of pollution are particularly concentrated around urban areas. Residence time of Cl in the watershed is estimated to be approximately 20 to 30years using a mixing model, suggesting that stream Cl concentrations likely will continue to rise for several decades.

Caspase Cleavages of the Lymphocyte-oriented Kinase Prevent Ezrin, Radixin, and Moesin Phosphorylation during Apoptosis.

The lymphocyte-oriented kinase (LOK), also called serine threonine kinase 10 (STK10), is synthesized mainly in lymphocytes. It is involved in lymphocyte migration and polarization and can phosphorylate ezrin, radixin, and moesin (the ERM proteins). In a T lymphocyte cell line and in purified human lymphocytes, we found LOK to be cleaved by caspases during apoptosis. The first cleavage occurs at aspartic residue 332, located between the kinase domain and the coiled-coil regulation domain. This cleavage generates an N-terminal fragment, p50 N-LOK, containing the kinase domain and a C-terminal fragment, which is further cleaved during apoptosis. Although these cleavages preserve the entire kinase domain, p50 N-LOK displays no kinase activity. In apoptotic lymphocytes, caspase cleavages of LOK are concomitant with a decrease in ERM phosphorylation. When non-apoptotic lymphocytes from mice with homozygous and heterozygous LOK knockout were compared, the latter showed a higher level of ERM phosphorylation, but when apoptosis was induced, LOK(-/-) and LOK(+/-) lymphocytes showed the same low level, confirming in vivo that LOK-induced ERM phosphorylation is prevented during lymphocyte apoptosis. Our results demonstrate that cleavage of LOK during apoptosis abolishes its kinase activity, causing a decrease in ERM phosphorylation, crucial to the role of the ERM proteins in linking the plasma membrane to actin filaments.