A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy

$\textit{Mycobacterium leprae}$ causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the $\textit{M. leprae}$-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of $\textit{M. leprae}$-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by $\textit{M. leprae}$ but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with $\textit{M. marinum}$-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to $\textit{M. leprae}$ PGL-1 in initiating nerve damage in leprosy.This work was supported by an A.P. Giannini Foundation Postdoctoral Fellowship, an NIH training grant (T32 AI1007411), and an NIH NRSA Postdoctoral Fellowship (AI104240) to C.A.M.; an NSF Predoctoral Fellowship and NIH training grant T32 AI55396 to C.J.C.; a UCLA Clinical Translational Science Institute grant (UL1TR001881 to K.K.S.); K08AR066545 to P.O.S.; U19AI111224 and R01AI049313 to D.B.M.; an NIH grant (R01AR064582) to A.S.; the NIH Director’s Pioneer Award, an NIH MERIT award (R37AI054503), and a Wellcome Trust Principal Research Fellowship to L.R

Iranian staff nurses' views of their productivity and human resource factors improving and impeding it: a qualitative study

BACKGROUND: Nurses, as the largest human resource element of health care systems, have a major role in providing ongoing, high-quality care to patients. Productivity is a significant indicator of professional development within any professional group, including nurses. The human resource element has been identified as the most important factor affecting productivity. This research aimed to explore nurses' perceptions and experiences of productivity and human resource factors improving or impeding it. METHOD: A qualitative approach was used to obtain rich data; open, semi-structured interviews were also conducted. The sampling was based on the maximum variant approach; data analysis was carried out by content analysis, with the constant comparative method. RESULTS: Participants indicated that human resources issues are the most important factor in promoting or impeding their productivity. They suggested that the factors influencing effectiveness of human resource elements include: systematic evaluation of staff numbers; a sound selection process based on verifiable criteria; provision of an adequate staffing level throughout the year; full involvement of the ward sister in the process of admitting patients; and sound communication within the care team. Paying attention to these factors creates a suitable background for improved productivity and decreases negative impacts of human resource shortages, whereas ignoring or interfering with them would result in lowering of nurses' productivity. CONCLUSION: Participants maintained that satisfactory human resources can improve nurses' productivity and the quality of care they provide; thereby fulfilling the core objective of the health care system

Population ecology of the sea lamprey (Petromyzon marinus) as an invasive species in the Laurentian Great Lakes and an imperiled species in Europe

The sea lamprey Petromyzon marinus (Linnaeus) is both an invasive non-native species in the Laurentian Great Lakes of North America and an imperiled species in much of its native range in North America and Europe. To compare and contrast how understanding of population ecology is useful for control programs in the Great Lakes and restoration programs in Europe, we review current understanding of the population ecology of the sea lamprey in its native and introduced range. Some attributes of sea lamprey population ecology are particularly useful for both control programs in the Great Lakes and restoration programs in the native range. First, traps within fish ladders are beneficial for removing sea lampreys in Great Lakes streams and passing sea lampreys in the native range. Second, attractants and repellants are suitable for luring sea lampreys into traps for control in the Great Lakes and guiding sea lamprey passage for conservation in the native range. Third, assessment methods used for targeting sea lamprey control in the Great Lakes are useful for targeting habitat protection in the native range. Last, assessment methods used to quantify numbers of all life stages of sea lampreys would be appropriate for measuring success of control in the Great Lakes and success of conservation in the native range

Malaria pigment crystals as magnetic micro-rotors: Key for high-sensitivity diagnosis

The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences. Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise. Here, we suggest an alternative optical methodology with an easy-to- use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study. Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme. These crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood. As a consequence, they can simultaneously act as magnetically driven micro-rotors and spinning polarizers in suspensions. These properties can gain importance not only in malaria diagnosis and therapies, where hemozoin is considered as drug target or immune modulator, but also in the magnetic manipulation of cells and tissues on the microscopic scale

Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior

Two genome duplications early in the vertebrate lineage expanded gene families, including GluN2 subunits of the NMDA receptor. Diversification between the four mammalian GluN2 proteins occurred primarily at their intracellular C−terminal domains (CTDs). To identify shared ancestral functions and diversified subunit−specific functions, we exchanged the exons encoding the GluN2A (also known as Grin2a) and GluN2B (also known as Grin2b) CTDs in two knock−in mice and analyzed the mice's biochemistry, synaptic physiology, and multiple learned and innate behaviors. The eight behaviors were genetically separated into four groups, including one group comprising three types of learning linked to conserved GluN2A/B regions. In contrast, the remaining five behaviors exhibited subunit−specific regulation. GluN2A/B CTD diversification conferred differential binding to cytoplasmic MAGUK proteins and differential forms of long−term potentiation. These data indicate that vertebrate behavior and synaptic signaling acquired increased complexity from the duplication and diversification of ancestral GluN2 gene

Physicochemical conditions and timing of rodingite formation: evidence from rodingite-hosted fluid inclusions in the JM Asbestos mine, Asbestos, Québec

Fluid inclusions and geological relationships indicate that rodingite formation in the Asbestos ophiolite, Québec, occurred in two, or possibly three, separate episodes during thrusting of the ophiolite onto the Laurentian margin, and that it involved three fluids. The first episode of rodingitization, which affected diorite, occurred at temperatures of between 290 and 360°C and pressures of 2.5 to 4.5 kbar, and the second episode, which affected granite and slate, occurred at temperatures of between 325 and 400°C and pressures less than 3 kbar. The fluids responsible for these episodes of alteration were moderately to strongly saline (~1.5 to 6.3 m eq. NaCl), rich in divalent cations and contained appreciable methane. A possible third episode of alteration is suggested by primary fluid inclusions in vesuvianite-rich bodies and secondary inclusions in other types of rodingite, with significantly lower trapping temperatures, salinity and methane content. The association of the aqueous fluids with hydrocarbon-rich fluids containing CH4 and higher order alkanes, but no CO2, suggests strongly that the former originated from the serpentinites. The similarities in the composition of the fluids in all rock types indicate that the ophiolite had already been thrust onto the slates when rodingitization occurred

Delayed granulomatous reaction to hyaluronic acid gel injection

Injectable hyaluronic acid (HA) derivatives are the most used resorbable dermal fillers used for soft tissue augmentation. While their use is considered safe, there have been reports of cutaneous granulomatous reactions.We describe the clinical, radiological, and cytological findings in a patient who presented a full year after cosmetic treatment with HA injections and discuss the various treatment options. Level of Evidence: Level V, therapeutic study

The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization

The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses

Predicting environmental chemical factors associated with disease-related gene expression data

<p>Abstract</p> <p>Background</p> <p>Many common diseases arise from an interaction between environmental and genetic factors. Our knowledge regarding environment and gene interactions is growing, but frameworks to build an association between gene-environment interactions and disease using preexisting, publicly available data has been lacking. Integrating freely-available environment-gene interaction and disease phenotype data would allow hypothesis generation for potential environmental associations to disease.</p> <p>Methods</p> <p>We integrated publicly available disease-specific gene expression microarray data and curated chemical-gene interaction data to systematically predict environmental chemicals associated with disease. We derived chemical-gene signatures for 1,338 chemical/environmental chemicals from the Comparative Toxicogenomics Database (CTD). We associated these chemical-gene signatures with differentially expressed genes from datasets found in the Gene Expression Omnibus (GEO) through an enrichment test.</p> <p>Results</p> <p>We were able to verify our analytic method by accurately identifying chemicals applied to samples and cell lines. Furthermore, we were able to predict known and novel environmental associations with prostate, lung, and breast cancers, such as estradiol and bisphenol A.</p> <p>Conclusions</p> <p>We have developed a scalable and statistical method to identify possible environmental associations with disease using publicly available data and have validated some of the associations in the literature.</p