Exploring Higher-Order Conceptual Learning in an Arthropod with a Large Multisensory Processing Center.

Comparative cognition aims to understand the evolutionary history and current function of cognitive abilities in a variety of species with diverse natural histories. One characteristic often attributed to higher cognitive abilities is higher-order conceptual learning, such as the ability to learn concepts independent of stimuli-e.g., 'same' or 'different'. Conceptual learning has been documented in honeybees and a number of vertebrates. Amblypygids, nocturnal enigmatic arachnids, are good candidates for higher-order learning because they are excellent associational learners, exceptional navigators, and they have large, highly folded mushroom bodies, which are brain regions known to be involved in learning and memory in insects. In Experiment 1, we investigate if the amblypygid Phrynus marginimaculatus can learn the concept of same with a delayed odor matching task. In Experiment 2, we test if Paraphrynus laevifrons can learn same/different with delayed tactile matching and nonmatching tasks before testing if they can transfer this learning to a novel cross-modal odor stimulus. Our data provide no evidence of conceptual learning in amblypygids, but more solid conclusions will require the use of alternative experimental designs to ensure our negative results are not simply a consequence of the designs we employed.

A comparison of farming- and non-farming-related suicides from the United States' National Violent Deaths Reporting System, 2003-2016.

Farmers are at higher risk of suicide than other occupations and the general population. The complex suicide risk factors have not been examined in a large, population-wide study across a significant time period. This observational study draws on existing data from the United States' National Violent Death Reporting System (NVDRS), including 140,523 farming- or non-farming-related suicide decedents between 2003 and 2016 from across 40 states. "Farming-related" decedents included 2,801 suicides. Farmers had higher odds of being male, older, less well-educated, and American Indian/Alaska Native. Farmers had higher odds of using firearms and-when farmers used a gun-higher odds of using a long-arm weapon. Farmers had lower odds of having a known mental health condition or job problem, and lower odds of having made a previous suicide attempt or leaving a suicide note. Findings highlight the complexity of suicide risk within the context of farming in the United States and reinforce the need for tailored prevention efforts; employing means restriction of firearms; and emphasizing that traditional risk factors may not be as common in the farming population.

Evolution of the sheep coat: the impact of domestication on its structure and development.

Wild sheep and many primitive domesticated breeds have two coats: coarse hairs covering shorter, finer fibres. Both are shed annually. Exploitation of wool for apparel in the Bronze Age encouraged breeding for denser fleeces and continuously growing white fibres. The Merino is regarded as the culmination of this process. Archaeological discoveries, ancient images and parchment records portray this as an evolutionary progression, spanning millennia. However, examination of the fleeces from feral, two-coated and woolled sheep has revealed a ready facility of the follicle population to change from shedding to continuous growth and to revert from domesticated to primitive states. Modifications to coat structure, colour and composition have occurred in timeframes and to sheep population sizes that exclude the likelihood of variations arising from mutations and natural selection. The features are characteristic of the domestication phenotype: an assemblage of developmental, physiological, skeletal and hormonal modifications common to a wide variety of species under human control. The phenotypic similarities appeared to result from an accumulation of cryptic genetic changes early during vertebrate evolution. Because they did not affect fitness in the wild, the mutations were protected from adverse selection, becoming apparent only after exposure to a domestic environment. The neural crest, a transient embryonic cell population unique to vertebrates, has been implicated in the manifestations of the domesticated phenotype. This hypothesis is discussed with reference to the development of the wool follicle population and the particular roles of Notch pathway genes, culminating in the specific cell interactions that typify follicle initiation.

Active Duty Personnel With ST Elevation Myocardial Infarctions Are Deployment Ineligible Despite Receiving Standard Management.

INTRODUCTION: ST elevation myocardial infarction (STEMI) is a high acuity diagnosis that requires prompt recognition and developed system responses to reduce morbidity and mortality. There is a paucity of literature describing active duty (AD) military personnel with STEMI syndromes at military treatment facilities (MTFs). This study aims to describe AD military members with STEMI diagnoses, military treatment facility management, and subsequent military dispositions observed. MATERIALS AND METHODS: We performed a single-center, retrospective review of all STEMI diagnoses at San Antonio Military Medical Center (SAMMC) from January 2008 to June 2018. Patients met inclusion in the analysis if they were (1) AD personnel in the United States Air Force (USAF) or United States Army (USA) and (2) presented with electrocardiogram findings and cardiac biomarkers diagnostic of a STEMI diagnosis. ASCVD and STEMI diagnoses were confirmed by board certified interventional cardiologists with coronary angiography. The 2017 American College of Cardiology (ACC) STEMI clinical performance and quality measures were used as the standard of care metrics for our case reviews. RESULTS: A total of 236 patients were treated for STEMI at SAMMC during the study period. Eight (3.4%) of these cases met inclusion criteria of being AD status at the time of diagnosis. Five (63%) of the AD STEMI diagnoses were USA members, three (37%) were USAF members, 50% were Caucasian, and 100% were male sex. The average age and body mass index were 46.3 ± 5.5 years old and 28.5 ± 3.1 kg/m 2, respectively. Preexisting cardiovascular risk factors were present in six (75%) of the individuals with hypertension being most common (63%). The eight patients had a baseline average low-density lipoprotein cholesterol of 110 ± 39 mg/dL, total cholesterol of 180 ± 49 mg/dL and calculated 10-year risk of atherosclerotic cardiovascular disease (ASCVD) 3.9 ± 1.6%. 100% of patients underwent primary percutaneous coronary intervention (PCI) within 90 minutes of presentation (average door-to-balloon time 59.3 ± 24 min). Single-vessel disease was found in all eight patients and seven of them underwent drug-eluting stent placement (average number of stents 2 ± 1.5). Performance and quality measures were met in all applicable categories including door-to-balloon times, discharge medical therapies, and cardiac rehabilitation enrollments for 100% AD personnel. Reported adverse events included two stent thromboses and two vascular complications. Three of eight individuals (37.5%) were diagnosed with behavioral health disorders secondary to their acute coronary syndrome. Medical retirement secondary to STEMI diagnosis occurred in 87.5% of subjects and all study personnel medically retired within 24 months (average 12.8 ± 7.9 months). CONCLUSIONS: AD personnel represent a small minority of MTF STEMI diagnoses and present with lower risk cardiovascular profiles. AD personnel received standard STEMI management compared to national performance measures, and were deployment ineligible after STEMI diagnoses. Further studies are needed to definitively explore the appropriate military dispositions for members with STEMI diagnoses and acute coronary syndromes.

Echocardiographic assessment of asymptomatic US Air Force members with early HIV infection.

OBJECTIVE: People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. However, there is scant evidence of the echocardiographic changes that occur shortly after seroconversion. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection and evaluated at the San Antonio Military Medical Center between September 1, 2015 and September 30, 2016. RESULTS: Patients (n = 50) were predominantly male (96%), mostly African American (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/µL. All were found to have normal left ventricular systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and left ventricular remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p > 0.05 for all).This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

Association of Endothelial Dysfunction and Antiretroviral Therapy in Early HIV Infection.

Importance: Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular disease (CVD) events. Endothelial dysfunction (EDF) is involved in CVD pathogenesis; however, EDF onset after HIV acquisition and the potential for reversibility with antiretroviral therapy (ART) have not been evaluated to date. Objective: To evaluate endothelial function with noninvasive reactive hyperemia index (RHI) in patients with early HIV infection at baseline and after ART initiation. Design, Setting, and Participants: Cohort study in which 61 members of the United States Air Force diagnosed with HIV infection from September 1, 2015, through September 30, 2017, were evaluated for baseline EDF. Natural log-transformed RHI values (lnRHI) of less than 0.51 and at least 0.51 were defined as abnormal and normal, respectively. The RHI interval changes were evaluated in a subgroup of 40 patients. Data were analyzed from September 30, 2017, through January 30, 2018. Exposure: Early HIV infection. Main Outcomes and Measures: Baseline EDF at HIV diagnosis and interval changes associated with ART initiation. Results: The 61 patients included in the analysis were predominantly male (58 [95%]) and mostly African American (35 [57%]), with a mean (SD) age of 28.1 (6.7) years at HIV diagnosis. Median time from estimated date of HIV seroconversion to RHI assessment was 10.6 months (interquartile range [IQR], 5.1-13.2 months), and the median CD4 lymphocyte count was 552/µL (IQR, 449/µL-674/µL). Patients had a mean (SD) body mass index of 26.2 (4.0), median (IQR) low-density lipoprotein cholesterol level of 97 (80-126) mg/dL, median (IQR) total cholesterol level of 163 (146-195) mg/dL, and no diabetes diagnoses. Overall mean (SD) lnRHI was 0.70 (0.29) at HIV diagnosis. Baseline RHI was normal in 47 patients (77%; mean [SD] lnRHI, 0.82 [0.20]) and was abnormal in 14 patients (23%; mean [SD] lnRHI, 0.30 [0.18]). Age (per 10-year increase) was not associated with an abnormal lnRHI (odds ratio, 2.15; 95% CI, 0.89-5.19; P = .09). Of the 41 patients with follow-up RHI assessments, 40 started ART immediately and repeated the RHI assessments at a median (IQR) of 6.4 (6.0-7.8) months. Use of ART was associated with an overall significan increase in mean (SD) lnRHI (0.13 [0.33]; P = .02). A greater increase in mean (SD) lnRHI was associated with abnormal (n = 11) compared with normal (n = 29) lnRHI at HIV diagnosis (0.33 [0.34]; P = .01 vs 0.04 [0.30]; P = .38). Among those with abnormal baseline lnRHI, 8 (73%) showed improved endothelial function after ART. The patient who declined ART converted from having a normal lnRHI (0.60) to an abnormal lnRHI (0.11) lnRHI after 8.3 months. Conclusions and Relevance: In this study, EDF was common in early HIV infection, with associated reversal in most patients taking ART. Results suggest that persistent EDF and CVD complications may be associated with delayed ART. Further studies are necessary to define the role of noninvasive endothelial function testing in patients with HIV infection.

Gradient variability in hypertrophic cardiomyopathy: New insights from computer-assisted, high fidelity, rest and exercise hemodynamic analysis.

OBJECTIVES: This study examines the intrapatient variability in peak instantaneous left ventricular outflow tract (LVOT) gradients and aortic pulse pressures during rest, exercise, and after ventricular ectopy. BACKGROUND: Although the variability in LVOT gradients in patients with hypertrophic cardiomyopathy (HCM) is well known, the predictors of such variation are not. We hypothesized that quantitative invasive analysis of gradient variation could identify useful predictors of maximal gradients. METHODS: Variability in continuously recorded, high-fidelity left ventricular and aortic pressure waveforms were evaluated by computer-assisted analysis in the resting state (N = 659 beats) and during supine exercise (N = 379 beats) in a symptomatic patient with a resting LVOT gradient >30 mmHg and frequent ventricular ectopy. RESULTS: At rest, the peak left ventricular and aortic pressures at the time of the peak instantaneous LVOT gradient for all sinus and postectopic beats followed consistent regression slopes characterizing the potential energy loss between the LV cavity and aorta. During exercise, similar regression slopes were identified, and these converged with the resting slopes at the point of the maximal measured LVOT gradient. Component analysis of the LVOT gradient suggests that resting beat-to-beat variability provides information similar to post-ectopic pressures for predicting maximal gradients in obstructive-variant HCM. CONCLUSIONS: Our study suggests that computer-assisted analysis of hemodynamic variability in HCM may prove useful in characterizing the severity of obstruction. Further study is warranted to confirm the reproducibility and utility of this finding in a population with clinically significant exercise-induced gradients.

Aviator's Heart: A Case of Athlete's Heart in an Active Duty Male Naval Aviator.

Athlete's heart is the condition of cardiac remodeling as a result of physiologic stress induced by regular strenuous physical activity by professional or elite amateur individuals. The literature describes several characteristics of the athletic heart, including left ventricular hypertrophy, increased left ventricular mass, right ventricular dilatation, atrial enlargement, electrocardiographic changes, and abnormalities on cardiac magnetic resonance imaging. We present a case of athletic heart in an exceptionally physically fit active duty naval aviator who experienced syncope and underwent extensive cardiac testing. He was found to have borderline hypertrophic changes as well as delayed gadolinium enhancement initially concerning for myocarditis. Cardiopulmonary exercise testing revealed an exercise capacity of 120% above the maximum measurable value for his age and gender. He was then diagnosed with athlete's heart and released to active duty with no limitations to his flight status. A challenge is posed to the practicing clinician in differentiating the athletic heart from the heart of an athlete suffering from underlying pathophysiology. Athlete's heart is an elusive diagnosis and may be associated with findings concerning for more insidious pathology, including hypertrophic cardiomyopathy and dilated cardiomyopathy. Additionally, patients with athlete's heart have been noted to have delayed gadolinium enhancement similar to that seen in patients with a history of myocarditis; the clinical significance of this finding is yet to be fully elucidated. In a military setting, distinguishing the heart of the healthy and athletic service member from the unfortunate one who has cardiomyopathy remains an important clinical distinction warranting further study.

Rest and exercise hemodynamic and metabolic findings in active duty soldiers referred for cardiac catheterization to exclude heart disease: Insights from past invasive cardiopulmonary exercise testing using multisensor high fidelity catheters.

OBJECTIVE: This study describes results of iCPET from the past, which used submaximal stress and multisensor high-fidelity catheters to exclude heart disease in a unique population of young adults. BACKGROUND: There has been resurgence in comprehensive hemodynamic evaluation of complex cardiovascular patients. Although dynamic assessments during cardiac catheterization have become commonplace, there remains limited information regarding left and right heart hemodynamic changes during supine exercise in young adults. METHODS: The study population was derived from a retrospective review of catheterization records at Brooke Army Medical Center for active duty patients (ages: 19-40 years) in whom hemodynamic waveforms were obtained with multisensor high-fidelity catheters and supine exercise testing (53.1 ± 12.6 watts) and angiography performed to exclude heart disease. We report findings from 41 males and 1 female (ages: 19-40 years) found free of heart disease. RESULTS: Submaximal exercise was associated with ≈ fourfold (P < 0.001) increase in minute ventilation (VE), O2 consumption (VO2 ) and carbon dioxide production (VCO2 ). VE/VCO2 ratio decreased (-16.8 ± 13.9%, P < 0.001) and VE/VCO2 slope was 22.6 ± 0.6 (±SE). Cardiac index (CI) increased with VO2 (ΔCI/ΔVO2 slope = 7.6 ± 2.2). Heart rate increased nearly 10 bpm per 100 mL O2 /min/M2 , whereas, changes in stroke volume were more variable. Pulmonary artery (PA) saturations fell from 77 to 55% (P < 0.001). No change was noted in mean right atrial pressures; PA pressures increased ≈10 mm Hg (P < 0.001). Pulmonary capillary wedge and left ventricular end-diastolic pressures increased ≈2 mm Hg (P < 0.001) but variability noted between individuals. CONCLUSION: This study provides insight into past practices of invasive cardiopulmonary testing and furthers the understanding of metabolic and hemodynamic changes in a young population during supine submaximal exercise. © 2017 Wiley Periodicals, Inc.

A case of Chagas cardiomyopathy following infection in south central Texas.

Between 5 and 8 million people globally are infected with Trypanosoma cruzi, the causative parasitic agent of Chagas disease. The vast majority of incident infections originate in pockets of Latin America where domestic vector-borne transmission cycles are more common. Since 1955, when the first locally-acquired case was reported, fewer than 30 autochthonous cases have been documented in the United States. We describe the case of an 18-year-old US Air Force trainee, a native Texan with no travel history beyond the continental United States, who screened positive for T cruzi infection on blood donation and was subsequently found to have chronic Chagasic cardiomyopathy. This is the first documented case of Chagas disease in a US military trainee and one of the first known autochthonous cases of Chagasic cardiomyopathy in a Texas resident. Diagnostic, therapeutic, and military implications are discussed.

Cardiovascular Complaints Among Military Members During Operation Enduring Freedom.

During Operation Enduring Freedom, the US military began deploying a dedicated theater cardiology consultant to Afghanistan in an effort to increase rates of return to duty in service members with cardiovascular complaints. This study was designed to categorize these complaints and determine the effect on both aeromedical evacuation and return to duty rates during a 2.5 year observation period. A total of 1,495 service members were evaluated, with 43% presenting due to chest pain followed by arrhythmias/palpitations (24.5%) and syncope (13.5%). Eighty-five percent of individuals returned to duty, most commonly with complaints of noncardiac chest pain, palpitations, or abnormal electrocardiograms. Fifteen percent were evacuated out of theater, most often with acute coronary syndrome, pulmonary embolus, or ventricular tachycardia. The forward-deployed theater cardiology consultant is vital in the disposition of military members by effectively parsing out life threatening cardiovascular conditions versus low risk diagnoses that can safely return to duty.

Impact of Enhanced External Counterpulsation on Heart Failure Rehospitalization in Patients With Ischemic Cardiomyopathy.

Heart failure (HF) affects millions of Americans and causes financial burdens because of the need for rehospitalization. For this reason, health care systems and patients alike are seeking methods to decrease readmissions. We assessed the potential for reducing readmissions of patients with postacute care HF through an educational program combined with enhanced external counterpulsation (EECP). We examined 99 patients with HF who were referred to EECP centers and received heart failure education and EECP treatment within 90 days of hospital discharge from March 2013 to January 2015. We compared observed and predicted 90-day readmission rates and examined results of 6-minute walk tests, Duke Activity Status Index, New York Heart Association classification, and Canadian Cardiovascular Society classification before and after EECP. Patients were treated with EECP at a median augmentation pressure of 280 mm Hg (quartile 1 = 240, quartile 3 = 280), achieved as early as the first treatment. Augmentation ratios varied from 0.4 to 1.9, with a median of 1.0 (quartile 1 = 0.8, quartile 3 = 1.2). Only 6 patients (6.1%) had unplanned readmissions compared to the predicted 34%, p <0.0001. The average increase in distance walked was 52 m (18.4%), and the median increase in Duke Activity Status Index was 9.95 points (100%), p values <0.0001. New York Heart Association and Canadian Cardiovascular Society classes improved in 61% and 60% of the patients, respectively. In conclusion, patients with HF who received education and EECP within 90 days of discharge had significantly lower readmission rates than predicted, and improved functional status, walk distance, and symptoms.

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure.

OBJECTIVES: The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). BACKGROUND: Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. METHODS: The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. RESULTS: A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. CONCLUSIONS: Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trial's untimely termination, additional AUF investigation is warranted.

Predictors of survival to orthotopic heart transplant in patients with light chain amyloidosis.

BACKGROUND: Orthotopic heart transplant (OHT), followed by myeloablative chemotherapy and autologous stem cell transplant (ASCT), has been successful in the treatment of amyloid light-chain (AL) cardiac amyloidosis. The purpose of this study was to identify predictors of survival to OHT in patients with end-stage heart failure due to AL amyloidosis and compare post-OHT survival of cardiac amyloid patients with survival of other cardiomyopathy patients undergoing OHT. METHODS: From January 2000 to June 2011, 31 patients with end-stage heart failure secondary to AL amyloidosis were listed for OHT at Massachusetts General Hospital. Univariate and multivariate regression analyses identified predictors of survival to OHT. Kaplan-Meier analysis compared survival between the Massachusetts General Hospital amyloidosis patients and non-amyloid cardiomyopathy patients from the Scientific Registry of Transplant Recipients (SRTR). RESULTS: Low body mass index was the only predictor of survival to OHT in patients with end-stage heart failure caused by cardiac amyloidosis. Survival of cardiac amyloid patients who died before receiving a donor heart was only 63 ± 45 days after listing. Patients who survived to OHT received a donor organ at 53 ± 48 days after listing. Survival of AL amyloidosis patients on the waiting list was less than patients on the waiting list for all other non-amyloid diagnoses. The long-term survival of amyloid patients who underwent OHT was no different than the survival of non-amyloid, restrictive (p = 0.34), non-amyloid dilated (p = 0.34), or all non-amyloid cardiomyopathy patients (p = 0.22) in the SRTR database. CONCLUSIONS: Amyloid patients who survive to OHT, followed by ASCT, have a survival rate similar to other cardiomyopathy patients undergoing OHT; however, 35% of the patients died awaiting OHT. The only predictor of survival to OHT in AL amyloidosis patients was a low body mass index, which correlated with a shorter time on the waiting list. To optimize the survival of these patients, access to donor organs must be improved.

A case of congenitally corrected transposition of the great arteries discovered on coronary computed tomography.

Congenitally corrected transposition of the great arteries is a rare condition accounting for less than 1% of all congenital cardiac diseases. The fundamental nature of this condition involves a blend of atrioventricular as well as ventriculoarterial discordance. Congenitally corrected transposition of the great arteries is classically associated with three additional abnormalities, including ventricular septal defect, right ventricular outflow tract obstruction, and tricuspid valve abnormalities. Patients with this anomaly have been shown to exhibit reduced exercise tolerance as well as reduced health-related quality of life when compared to patients with normal cardiovascular anatomy. We present the case of a 33-year-old active duty lieutenant in the United States Air Force referred to the cardiology clinic for evaluation of valvular heart disease with subsequent discovery of congenitally corrected transposition of the great arteries on cardiac gated computed tomography.

Drosophila embryos close epithelial wounds using a combination of cellular protrusions and an actomyosin purse string.

The repair of injured tissue must occur rapidly to prevent microbial invasion and maintain tissue integrity. Epithelial tissues in particular, which serve as a barrier against the external environment, must repair efficiently in order to restore their primary function. Here we analyze the effect of different parameters on the epithelial wound repair process in the late stage Drosophila embryo using in vivo wound assays, expression of cytoskeleton and membrane markers, and mutant analysis. We define four distinct phases in the repair process, expansion, coalescence, contraction and closure, and describe the molecular dynamics of each phase. Specifically, we find that myosin, E-cadherin, Echinoid, the plasma membrane, microtubules and the Cdc42 small GTPase respond dynamically during wound repair. We demonstrate that perturbations of each of these components result in specific impairments to the wound healing process. Our results show that embryonic epithelial wound repair is mediated by two simultaneously acting mechanisms: crawling driven by cellular protrusions and actomyosin ring contraction along the leading edge of the wound.

Cytoskeleton responses in wound repair.

Wound repair on the cellular and multicellular levels is essential to the survival of complex organisms. In order to avoid further damage, prevent infection, and restore normal function, cells and tissues must rapidly seal and remodel the wounded area. The cytoskeleton is an important component of wound repair in that it is needed for actomyosin contraction, recruitment of repair machineries, and cell migration. Recent use of model systems and high-resolution microscopy has provided new insight into molecular aspects of the cytoskeletal response during wound repair. Here we discuss the role of the cytoskeleton in single-cell, embryonic, and adult repair, as well as the striking resemblance of these processes to normal developmental events and many diseases.

VAMP4- and VAMP7-expressing vesicles are both required for cytotoxic granule exocytosis in NK cells.

NK cells eliminate cancer and virus-infected cells through their cytolytic activity. The last step in NK-cell cytotoxicity, resulting in exocytosis of granule content, requires fusion of lytic granules with the plasma membrane. Proteins from the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion events in the cell. Here, we show that NK cells express all members of the R-SNARE subgroup. Two of these R-SNARE proteins, VAMP4 and VAMP7, colocalize with lytic granules during cytotoxic interactions. However, only VAMP7 associates with perforin-containing granules in nonactivated cells, indicating that the two VAMPs have different functions in exocytosis. Using both the tumor NK-cell line YTS and the peripheral NK cells, we show that the disruption of expression of either VAMP4 or VAMP7 inhibits the release of lytic granules and severely impairs NK-cell cytotoxic activity. Furthermore, VAMP7 but not VAMP4 is involved in IFN-γ secretion in NK cells, indicating that VAMP7 is involved in many fusion processes and thus plays a more general function in NK-cell activity than VAMP4.

A proteomic (SELDI-TOF-MS) approach to estrogen agonist screening.

A small fish model and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry were used to investigate plasma protein expression as a means to screen chemicals for estrogenic activity. Adult male sheepshead minnows (Cyprinodon variegatus) were placed into aquaria for seawater control, solvent control, and treatments of 17beta-estradiol (E2), methoxychlor (MXC), bisphenol-A (BPA), 4-tert-pentylphenol (TPP), endosulfan (ES), and chlorpyriphos (CP). Fish plasma was applied to weak cation exchange (CM10) ProteinChip arrays, processed, and analyzed. The array produced approximately 42 peaks for E2 plasma and 30 peaks for solvent control plasma. Estrogen-responsive mass spectral biomarker peaks were identified by comparison of E2-treated and control plasma spectra. Thirteen potential protein biomarkers with a range from 1 to 13 kDa were up- or downregulated in E2-treated fish and their performance as estrogenic effects markers was evaluated by comparing spectra from control, estrogen agonist, and nonagonist stressor-treated males and normal female fish plasma. One of the biomarkers, mass-to-charge ratio 3025.5, was identified by high-resolution tandem mass spectrometry as C. variegatus zona radiata protein, fragment 2. The weak environmental estrogens MXC, BPA, and TPP elicited protein expression profiles consistent with the estrogen expression model. Estrogen-responsive peaks were not detected in plasma from fish in the seawater, vehicle, ES, or CP treatments. No difference was found between plasma protein expression of seawater control and solvent control fish. We show that water exposure of fish to estrogen agonists produces distinct plasma protein biomarkers that can be reproducibly detected at low levels using protein chips and mass spectrometry.