Habitat structure changes the relationships between predator behavior, prey behavior, and prey survival rates.

The individual behavioral traits of predators and prey sometimes determine the outcome of their interactions. Here, we examine whether changes to habitat complexity alter the effects of predator and prey behavior on their survival rates. Specifically, we test whether behavioral traits (activity level, boldness, and perch height) measured in predators and prey or multivariate behavioral volumes best predict the survival rates of both trophic levels in staged mesocosms with contrasting structural complexity. Behavioral volumes and hypervolumes are a composite group-level behavioral diversity metric built from the individual-level behavioral traits we measured in predators and prey. We stocked mesocosms with a host plant and groups of cannibalistic predators (n = 5 mantises/mesocosm) and their prey (n = 15 katydids/mesocosm), and mesocosms varied in the presence/absence of additional non-living climbing structures. We found that mantis survival rates were unrelated to any behavioral metric considered here, but were higher in structurally complex mesocosms. Unexpectedly, katydids were more likely to survive when mantis groups occupied larger behavioral volumes, indicating that more behaviorally diverse predator groups are less lethal. Katydid mortality was also increased when both predators and prey exhibited higher average perch heights, but this effect was increased by the addition of supplemental structure. This is consistent with the expectation that structural complexity increases the effect of intraspecific behavioral variation on prey survival rates. Collectively, these results convey that the effects of predator and prey behavior on prey survival could depend highly on the environment in which they are evaluated.

Occupational medicine clinical practice data reveal increased injury rates among Hispanic workers.

BACKGROUND: Minnesota has an ethnically diverse labor force, with the largest number of refugees per capita in the United States. In recent years, Minnesota has been and continues to be a major site for immigrant and refugee resettlement in the United States, with a large population of both immigrant and native born Hmong, Hispanic, and East Africans. This study seeks to evaluate the injury risk among the evolving minority workforce in the Minnesota Twin Cities region. METHODS: A retrospective cohort study identifying work-related injuries following pre-employment examinations was performed using electronic health records from a large multi-clinic occupational medicine practice. Preplacement examinations and subsequent work-related injuries were pulled from the electronic health record using representative ICD-10 codes for surveillance examinations and injuries. This study included patient records collected over a 2-year period from January 1, 2015, through December, 2016. The patients in this cohort worked in a wide-array of occupations including production, assembly, construction, law enforcement, among others. RESULTS: Hispanic minority workers were twice as likely to be injured at work compared with White workers. Hispanics were 2.89 times more likely to develop back injuries compared with non-Hispanic workers, and 1.86 times more likely to develop upper extremity injuries involving the hand, wrist, or elbow. CONCLUSION: Clinical practice data shows that Hispanic workers are at increased risk for work-related injuries in Minnesota. They were especially susceptible to back and upper extremity injuries. Lower injury rates in non-Hispanic minority workers, may be the result of injury underreporting and require further investigation.

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster.

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug's impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

Mechano-capacitive properties of polarized membranes.

Biological membranes are capacitors that can be charged by applying a field across the membrane. The charges on the capacitor exert a force on the membrane that leads to electrostriction, i.e. a thinning of the membrane. Since the force is quadratic in voltage, negative and positive voltage have an identical influence on the physics of symmetric membranes. However, this is not the case for a membrane with an asymmetry leading to a permanent electric polarization. Positive and negative voltages of identical magnitude lead to different properties. Such an asymmetry can originate from a lipid composition that is different on the two monolayers of the membrane, or from membrane curvature. The latter effect is called 'flexoelectricity'. As a consequence of permanent polarization, the membrane capacitor is discharged at a voltage different from zero. This leads to interesting electrical phenomena such as outward or inward rectification of membrane permeability. Here, we introduce a generalized theoretical framework, that treats capacitance, polarization, flexoelectricity, piezoelectricity and thermoelectricity in the same language. We show applications to electrostriction, membrane permeability and piezoelectricity and thermoelectricity close to melting transitions, where such effects are especially pronounced.

Thermal-work strain in law enforcement personnel during chemical, biological, radiological, and nuclear (CBRN) training.

BACKGROUND: Thermal safety standards for the use of chemical, biological, radiological, and nuclear (CBRN) ensembles have been established for various US occupations, but not for law enforcement personnel. OBJECTIVES: We examined thermal strain levels of 30 male US law enforcement personnel who participated in CBRN field training in Arizona, Florida, and Massachusetts. METHODS: Physiological responses were examined using unobtrusive heart rate (HR) monitors and a simple thermoregulatory model to predict core temperature (Tc) using HR and environment. RESULTS: Thermal strain levels varied by environments, activity levels, and type of CBRN ensemble. Arizona and Florida volunteers working in hot-dry and hot-humid environment indicated high heat strain (predicted max Tc>38·5°C). The cool environment of Massachusetts reduced thermal strain although thermal strains were occasionally moderate. CONCLUSIONS: The non-invasive method of using physiological monitoring and thermoregulatory modeling could improve law enforcement mission to reduce the risk of heat illness or injury.

ECHO Autism Washington: Autism Diagnostic Evaluations in Primary Care.

ECHO (Extensions for Community Healthcare Outcomes) Autism is a telementoring learning model to increase community capacity for autism-related health care. Seventy-seven pediatric providers (mostly primary care, seeing exclusively Medicaid patient populations) enrolled in 1 year of ECHO Autism Washington. Analysis of self-report surveys showed a significant increase in autism diagnoses made by ECHO providers after 1 year, F(1, 65) = 7.52, P = .008. Providers who attended more sessions reported making more diagnoses, F(2, 613.26), P = .045. Of note, autism diagnoses were not externally validated. The total number of reported barriers reduced, F(2, 61) = 13.5), P < .001, and confidence ratings increased F(2, 60) = 24.21, P < .001. The average number of diagnostic referrals from ECHO providers to the state's largest autism specialty clinic significantly reduced, t(43) = 4.23, P < .001, with significantly fewer diagnostic referrals made during and after ECHO training compared with a comparison group of 28 non-ECHO providers, t(58.77) = -3.36, P < .001. Overall, 1 year of ECHO Autism Washington participation led to significant changes in autism diagnostic practices.

A stem cell-based assay platform demonstrates alpha-synuclein dependent synaptic dysfunction in patient-derived cortical neurons.

Alpha-synuclein (αS)-rich Lewy bodies and neurites in the cerebral cortex correlate with the presence of dementia in Parkinson disease (PD) and Dementia with Lewy bodies (DLB), but whether αS influences synaptic vesicle dynamics in human cortical neurons is unknown. Using a new iPSC-based assay platform for measuring synaptic vesicle cycling, we found that in human cortical glutamatergic neurons, increased αS from either transgenic expression or triplication of the endogenous locus in patient-derived neurons reduced synaptic vesicle cycling under both stimulated and spontaneous conditions. Thus, using a robust, easily adopted assay platform, we show for the first time αS-induced synaptic dysfunction in human cortical neurons, a key cellular substrate for PD dementia and DLB.

Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells.

The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March-I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I-deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II-specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitin-dependent degradation of internalized pMHC-II.

Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis.

GATA-3 is one member of a growing family of related transcription factors which share a strongly conserved expression pattern in all vertebrate organisms. In order to elucidate GATA-3 function using a direct genetic approach, we have disrupted the murine gene by homologous recombination in embryonic stem cells. Mice heterozygous for the GATA3 mutation are fertile and appear in all respects to be normal, whereas homozygous mutant embryos die between days 11 and 12 postcoitum (p.c.) and display massive internal bleeding, marked growth retardation, severe deformities of the brain and spinal cord, and gross aberrations in fetal liver haematopoiesis.

The ethical imperative to honor autistic clients' autonomy in mental health treatment.

Autistic adolescents and adults commonly experience mental health concerns; however, mental health clinicians may hold implicit stigmatizing views of autism that contribute to case conceptualization and treatment goal setting that align more with caregivers' than clients' goals. This impingement on client autonomy is concerning, problematic, and potentially harmful for autistic clients who are of an age to set their own treatment agenda regardless of co-occurring intellectual disability and/or language delays. An application of the shared decision-making framework, an evidence-based tool for promoting client autonomy, can help to avoid these challenges in treatment. In this perspective, we use a case vignette as an anchor for discussing the imperative of honoring autistic clients' autonomy in mental health treatment and guiding shared decision-making to reduce stigma, promote autonomy, and increase collaborative care for autistic clients in mental health treatment.

Dendritic cell activation prevents MHC class II ubiquitination and promotes MHC class II survival regardless of the activation stimulus.

The expression of MHC class II (MHC-II) on the surface of antigen-presenting cells, such as dendritic cells (DCs), is tightly regulated during cellular activation. Many cells, including DCs, are activated following stimulation of innate Toll-like receptors (TLRs) by products of microorganisms. In the resting (immature) state, MHC-II is ubiquitinated in immature DCs and is rapidly degraded; however, after activation of these cells with MyD88-dependent TLR ligands, MHC-II ubiquitination is blocked, and MHC-II survival is prolonged. We now show that DC activation using MyD88-dependent TLR ligands, MyD88-independent TLR ligands, and even infection with the intracellular parasite Toxoplasma gondii leads to identical changes in MHC-II expression, ubiquitination, and surface stability, revealing a conserved role for enhanced MHC-II stability after DC activation by different stimuli.

The POU factor Oct-6 and Schwann cell differentiation.

The POU transcription factor Oct-6, also known as SCIP or Tst-1, has been implicated as a major transcriptional regulator in Schwann cell differentiation. Microscopic and immunochemical analysis of sciatic nerves of Oct-6(-/-) mice at different stages of postnatal development reveals a delay in Schwann cell differentiation, with a transient arrest at the promyelination stage. Thus, Oct-6 appears to be required for the transition of promyelin cells to myelinating cells. Once these cells progress past this point, Oct-6 is no longer required, and myelination occurs normally.

Localization of distant urogenital system-, central nervous system-, and endocardium-specific transcriptional regulatory elements in the GATA-3 locus.

We found previously that neither a 6-kbp promoter fragment nor even a 120-kbp yeast artificial chromosome (YAC) containing the whole GATA-3 gene was sufficient to recapitulate its full transcription pattern during embryonic development in transgenic mice. In an attempt to further identify tissue-specific regulatory elements modulating the dynamic embryonic pattern of the GATA-3 gene, we have examined the expression of two much larger (540- and 625-kbp) GATA-3 YACs in transgenic animals. A lacZ reporter gene was first inserted into both large GATA-3 YACs. The transgenic YAC patterns were then compared to those of embryos bearing the identical lacZ insertion in the chromosomal GATA-3 locus (creating GATA-3/lacZ "knock-ins"). We found that most of the YAC expression sites and tissues are directly reflective of the endogenous pattern, and detailed examination of the integrated YAC transgenes allowed the general localization of a number of very distant transcriptional regulatory elements (putative central nervous system-, endocardium-, and urogenital system-specific enhancers). Remarkably, even the 625-kbp GATA-3 YAC, containing approximately 450 kbp and 150 kbp of 5' and 3' flanking sequences, respectively, does not contain the full transcriptional regulatory potential of the endogenous locus and is clearly missing regulatory elements that confer tissue-specific expression to GATA-3 in a subset of neural crest-derived cell lineages.

GATA-3 is involved in the development of serotonergic neurons in the caudal raphe nuclei.

The GATA-3 transcription factor shows a specific and restricted expression pattern in the developing and adult mouse brain. In the present study we investigated the role of GATA-3 in the caudal raphe system, which is known to operate as a modulator of motor activity. We demonstrate that virtually all neurons in the caudal raphe nuclei that express GATA-3 also produce serotonin. Absence of GATA-3, as analyzed in chimeric -/- mice, affects the cytoarchitecture of serotonergic neurons in the caudal raphe nuclei. As a result the chimeras show a serious defect in their locomotor performance on a rotating rod. In sum, we conclude that GATA-3 plays a major role in the development of the serotonergic neurons of the caudal raphe nuclei, and that it is crucial for their role in locomotion.

The Effect of the Nonlinearity of the Response of Lipid Membranes to Voltage Perturbations on the Interpretation of Their Electrical Properties. A New Theoretical Description.

Our understanding of the electrical properties of cell membranes is derived from experiments where the membrane is exposed to a perturbation (in the form of a time-dependent voltage or current change) and information is extracted from the measured output. The interpretation of such electrical recordings consists in finding an electronic equivalent that would show the same or similar response as the biological system. In general, however, there is no unique circuit configuration, which can explain a single electrical recording and the choice of an electric model for a biological system is based on complementary information (most commonly structural information) of the system investigated. Most of the electrophysiological data on cell membranes address the functional role of protein channels while assuming that the lipid matrix is an insulator with constant capacitance. However, close to their melting transition the lipid bilayers are no inert insulators. Their conductivity and their capacitance are nonlinear functions of both voltage, area and volume density. This has to be considered when interpreting electrical data. Here we show how electric data commonly interpreted as gating currents of proteins and inductance can be explained by the nonlinear dynamics of the lipid matrix itself.

Transcription factor GATA-3 alters pathway selection of olivocochlear neurons and affects morphogenesis of the ear.

Patterning the vertebrate ear requires the coordinated expression of genes that are involved in morphogenesis, neurogenesis, and hair cell formation. The zinc finger gene GATA-3 is expressed both in the inner ear and in afferent and efferent auditory neurons. Specifically, GATA-3 is expressed in a population of neurons in rhombomere 4 that extend their axons across the floor plate of rhombomere 4 (r4) at embryonic day 10 (E10) and reach the sensory epithelia of the ear by E13.5. The distribution of their cell bodies corresponds to that of the cell bodies of the cochlear and vestibular efferent neurons as revealed by labeling with tracers. Both GATA-3 heterozygous and GATA-3 null mutant mice show unusual axonal projections, such as misrouted crossing fibers and fibers in the facial nerve, that are absent in wild-type littermates. This suggests that GATA-3 is involved in the pathfinding of efferent neuron axons that navigate to the ear. In the ear, GATA-3 is expressed inside the otocyst and the surrounding periotic mesenchyme. The latter expression is in areas of branching of the developing ear leading to the formation of semicircular canals. Ears of GATA-3 null mutants remain cystic, with a single extension of the endolymphatic duct and no formation of semicircular canals or saccular and utricular recesses. Thus, both the distribution of GATA-3 and the effects of null mutations on the ear suggest involvement of GATA-3 in morphogenesis of the ear. This study shows for the first time that a zinc finger factor is involved in axonal navigation of the inner ear efferent neurons and, simultaneously, in the morphogenesis of the inner ear.

Francisella tularensis elicits IL-10 via a PGE2-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation.

Francisella tularensis is a bacterial pathogen that uses host-derived PGE2 to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE2 acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE2 can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensismacrophage supernatant), which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 "resistant" class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE2 can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE2 drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE2, these results suggest that a yet-to-be-identified PGE2-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens.

Deletion of SNAP-23 results in pre-implantation embryonic lethality in mice.

SNARE-mediated membrane fusion is a pivotal event for a wide-variety of biological processes. SNAP-25, a neuron-specific SNARE protein, has been well-characterized and mouse embryos lacking Snap25 are viable. However, the phenotype of mice lacking SNAP-23, the ubiquitously expressed SNAP-25 homolog, remains unknown. To reveal the importance of SNAP-23 function in mouse development, we generated Snap23-null mice by homologous recombination. We were unable to obtain newborn SNAP-23-deficient mice, and analysis of pre-implantation embryos from Snap23(Δ/wt) matings revealed that Snap23-null blastocysts were dying prior to implantation at embryonic day E3.5. Thus these data reveal a critical role for SNAP-23 during embryogenesis.

Assistive device use as a dynamic acquisition process in later life.

PURPOSE: This study identifies risk factors, including incident disability, for the use of assistive devices (ADs) among older people. DESIGN AND METHODS: Three waves of data from the National Long-Term Care Survey (NLTCS) are used to examine whether upper and lower body disability lead to use of ADs (both number of devices used and number of activities of daily living domains for which ADs are used). Predictors of AD use include demographic variables, body mass index, and disability (both initial and incident). Relationships are estimated with negative binomial regression models. RESULTS: Lower body disability, advanced age, and obesity are consistent predictors of the number of ADs used. An interaction between age and incident disability revealed the highest rate of adoption among the younger respondents who experienced increases in disability. IMPLICATIONS: Many older adults use ADs in response to the disablement process. In addition to need driven by rising disability, obese older adults use more ADs. Results from this study clarify who and why ADs are adopted by older persons and should facilitate effective intervention by health care personnel and caregivers.

Alpha-synuclein A30P point-mutation generates age-dependent nigrostriatal deficiency in mice.

Lewy bodies are mainly composed of alpha-synuclein (SNCA) and specific mutations in SNCA gene are related to familial forms of Parkinson's disease (PD). The purpose of our study was to generate a mouse line with A30P knock-in point mutation in SNCA gene and to test if a single point-mutation is able to turn otherwise normal SNCA into a toxic form. The behavioral profile of SNCA A30P mice was followed for 16 months. Generally, these mice are healthy and viable without any obvious abnormalities. Starting from the age of 13 months mice developed a significant deficit in motor performance tests related to nigrostriatal function (ink-test and beam walk). In other tests (motility boxes, rotarod) mice continuously performed normally. Moreover, SNCA A30P mice expressed the altered sensitivity to VMAT2 inhibitor reserpine, possibly reflecting a functional deficiency of dopamine. Indeed, mice at 15 months of age had significantly reduced levels of dopamine and its major metabolite DOPAC in the striatum, and reduced levels of dopamine in the mesolimbic system. The present study confirms that SNCA plays an important role in the development of PD and an insertion of a single point mutation is sufficient to generate age-related decline in specific motor performance. The generated mouse line has a potential to become a model for PD with comparable time course and phenotype.