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H2-Driven NADH regeneration has long suffered from low selectivity when non-enzymatic, particularly heterogeneous catalysts, are used. In addition to the unselective nature of the catalysts, the typically unmeasured NAD+ conversion has inevitably hindered catalyst development. Here we report Sn-doped Pt/SiO2 catalysts for the selective regeneration of NADH and show that doping Pt/SiO2 with 10 at% Sn can deliver a selectivity of 90% (at full conversion) using H2. We propose that this is a result of Sn disturbing the Pt ensemble, altering the mode of NAD+ adsorption and directing the reduction to the 1,4-position of the nicotinamide ring. [ABSTRACT FROM AUTHOR]

NAD(P)H is a key cofactor widely used in biocatalytic reductive transformations, facilitating a wide range of industrially significant reactions which ultimately result in the consumption of the costly cofactor. To make NAD(P)H dependent biotransformations sustainable and economically feasible, different catalytic routes have been investigated to regenerate NAD(P)H. Here we report a comprehensive life cycle assessment (LCA) of these catalytic regeneration methods. Midpoint characterisation and normalisation show that the synthesis of the catalyst, specifically the use of noble metals and energy consumption, dominate the environmental impacts and have the greatest contribution to all considered impact categories. This comparative LCA highlights the need for future investigation into noble metal based catalyst alternatives, to provide cleaner and more sustainable methods of regenerating the cofactor NAD(P)H. [ABSTRACT FROM AUTHOR]

Global bifurcation and spatio-temporal patterns of periodic solutions (with prescribed period) to second order reversible equivariant autonomous systems with commensurate delays are studied using the Brouwer/Leray–Schauder O (2) × Γ × ℤ 2 -equivariant degree theory. Here, O (2) is related to the reversal symmetry combined with the autonomous form of the system, Γ reflects extra spacial symmetries of the system, and ℤ 2 is related to the oddness of the right-hand side. Abstract results are supported by a concrete example with Γ = D 6 — the dihedral group of order 12. [ABSTRACT FROM AUTHOR]

This study demonstrates a novel method to quantify selective (1,4-NADH) and unselective products (1,2- and 1,6-NADH) in NADH regeneration using combined UV-Vis spectroscopy and biological assays. The validity of the proposed method was tested in the Pt/C promoted NAD+ hydrogenation using hydrogen as reducing agent. [ABSTRACT FROM AUTHOR]

• NAD(P)H regeneration cleanliness is crucial for sustainable biotransformations. • First assessment of environmental impact of NAD(P)H regeneration methods. • Heterogeneous catalysis and electrocatalysis produce the lowest amount of waste. • Recyclable heterogeneous Pt/Fe 3 O 4 catalyst exhibits an E-factor of ∼1 using H 2. Cofactor (reduced) Nicotinamide Adenine Dinucleotide (NAD(P)H) is an energy carrier in enzymatic redox reactions that are employed for the synthesis of valuable chemicals and pharmaceuticals. The high cost of NAD(P)H makes it impractical to use in stoichiometric amounts in industrial processes. This has led to the development of a variety of methods for NAD(P)H regeneration. In this work, process cleanliness of the current NADH recycling systems was evaluated using E-factor (kg waste /kg NADH) as a green chemistry metric. The E-factor obtained, depending on the process method, reaches values higher than 20000, where non-recyclable agents, including sacrificial hydride/electron donors, catalysts and electron mediators, alongside by-products (from cosubstrates), account for the overall waste. A promising alternative methodology for NADH regeneration using H 2 and recyclable Pt/Fe 3 O 4 is presented and characterisation performed by temperature-programmed reduction (TPR), nitrogen adsorption (surface area/porosity), powder X-ray diffraction (XRD) and transmission electron microscopy (TEM) is used to elucidate the observed performance. The Pt/Fe 3 O 4 system at room temperature delivers a turnover frequency of 20 h−1 and the catalyst can be recycled for reuse, producing a significantly low level of waste (E-factor = ∼1). [ABSTRACT FROM AUTHOR]

We consider a generalized type of unique factorization of the positive integers with restrictions on the exponents and view them as a family of arithmetic convolutions and divisibility relations, similar to the convolutions defined by Narkewicz [On a class of arithmetical convolutions, Colloq. Math.10 (1963) 81–94]. We introduce special types of multiplicativity corresponding to these convolutions, and discuss algebraic properties of the associated arithmetic convolutions and analogs of the Möbius functions. We also prove asymptotics for analogs of the totient function, totient summatory function, and divisor summatory function. [ABSTRACT FROM AUTHOR]

The k-ary divisibility relations are a class of recursively defined relations beginning with standard divisibility and culminating in the so-called infinitary divisibility relation. We examine the summatory functions corresponding to the k-ary analogues of various popular functions in number theory, proving various results about the structure of the k-ary divisibility relations along the way. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) typically exhibits rapid progression, high mortality and faster relapse rates relative to other breast cancer subtypes. In this report we examine the combination of taxanes (paclitaxel or docetaxel) with a breast cancer stem cell (CSC)-targeting agent sulforaphane for use against TNBC. We demonstrate that paclitaxel or docetaxel treatment induces IL-6 secretion and results in expansion of CSCs in TNBC cell lines. Conversely, sulforaphane is capable of preferentially eliminating CSCs, by inhibiting NF-κB p65 subunit translocation, downregulating p52 and consequent downstream transcriptional activity. Sulforaphane also reverses taxane-induced aldehyde dehydrogenase-positive (ALDH+) cell enrichment, and dramatically reduces the size and number of primary and secondary mammospheres formed. In vivo in an advanced treatment orthotopic mouse xenograft model together with extreme limiting dilution analysis (ELDA), the combination of docetaxel and sulforaphane exhibits a greater reduction in primary tumor volume and significantly reduces secondary tumor formation relative to either treatment alone. These results suggest that treatment of TNBCs with cytotoxic chemotherapy would be greatly benefited by the addition of sulforaphane to prevent expansion of and eliminate breast CSCs. [ABSTRACT FROM AUTHOR]

Abstract: Envenomation syndromes induced by Atlantic cnidaria have been tabulated and their therapy discussed. The pharmacokinetics of the venom has been emphasized. Pain occurs instantly and reaches a zenith rapidly in the surf. The nematocysts have already penetrated the dermis and disease proceeds before help can arrive. This fact plus the relative impermeability of human epidermis hampers the efficacy of topical agents. Oral analgesics, the agents of choice, are seldom offered and systemic administration of these drugs is usually not necessary. The use of hot or cold applications has not been settled. Measures to inactivate nematocysts within tentacles adherent to skin post-sting have been demonstrated in vitro, but the clinical significance of these actions has not been shown. Using an abrader (sand, crystalline papain) to counter-irritate nearby skin might provide relief. Antivenoms for Atlantic cnidaria are not available. The instances when verapamil might be employed are very rare. The reasons for the increasing case load of these injuries are discussed and the need to discover more effective therapeutic agents is emphasized. [Copyright &y& Elsevier]

Human figure drawings of patients with severe (n = 85) and mild (n = 38) psoriasis were compared on dimensions of nudity, sexual overemphasis, and omissions of exposed body parts. For female patients significant differences were found for percentages of undressed figures and omissions. For male patients only omissions were significant. When compared to 30 patients with other mild dermatologic conditions, mildly affected psoriatic males drew significantly fewer omissions. Discussion of results focussed on body image concerns, of dermatology patients as related to issues of nudity, sexuality, and exhibition of exposed body parts. [ABSTRACT FROM AUTHOR]

Sea nettle toxin was found to increase the short-circuit current across isolated frog skin. This effect was blocked by hyperimmune serum but not by calcium chloride. In vitro guinea pig kidney (Na + K) ATPase was unaffected by the toxin. The rise in short-circuit current was mimicked by vasopressin but tissue level of 3'5' cyclic AMP were not found to be elevated over controls. [ABSTRACT FROM AUTHOR]

A series of ceria–zirconia mixed metal oxides with varying metal ratios were prepared by the calcination of precursors synthesized by mechanochemical grinding of the metal carbonates, and tested for catalytic naphthalene and propane total combustion. The mechanically-mixed metal oxides were more active for both propane and naphthalene total oxidation compared to the parent metal oxides. Ce0.95Zr0.05Ox was the most active catalyst for the total combustion of propane and naphthalene. Catalysts were characterized by x-ray diffraction, BET surface area, laser Raman spectroscopy, temperature programmed reduction, scanning electron microscopy with energy dispersive x-ray analysis and x-ray photoelectron spectroscopy techniques. Formation of ceria–zirconia solid solutions was observed for catalysts with a zirconia content of 10% or lower, whereas ceria and zirconia phase separation was observed when zirconia content was above 25%. Surface area increased when ceria and zirconia were mixed, and the reduction temperature of the bulk shifted to lower temperatures upon increasing zirconia content. Incorporation of zirconia was found to increase the relative concentration of surface oxygen defects compared to pure ceria, with low amounts of zirconia showing the greatest increase. The concentration of oxygen defects correlates with propane and naphthalene total oxidation activity. The enhanced total oxidation activity occurs as a result of the increased number of oxygen defects and the higher surface area. The results demonstrate that mechanochemical preparation from carbonate precursors was an effective route to make active catalysts. [ABSTRACT FROM AUTHOR]

Although trastuzumab is an effective treatment in early stage HER2+ breast cancer the majority of advanced HER2+ breast cancers develop trastuzumab resistance, especially in the 40% of breast cancers with loss of PTEN. However, HER2+ breast cancer patients continue to receive trastuzumab regardless PTEN status and the consequence of therapy in these patients is unknown. We demonstrate that continued use of trastuzumab in HER2+ cells with loss of PTEN induces the epithelial-mesenchymal transition (EMT) and transform HER2+ to a triple negative breast cancer. These transformed cells exhibited mesenchymal morphology and gene expression markers, while parent HER2+ cells showed epithelial morphology and markers. The transformed cells exhibited loss of dependence on ERBB family signaling (such as HER2, HER3, HER4, BTC, HRG, EGF) and reduced estrogen and progesterone receptors. Continued use of trastuzumab in HER2+ PTEN− cells increased the frequency of cancer stem cells (CSCs) and metastasis potential. Strikingly, parental HER2+ cells and transformed resistant cells respond to treatment differently. Transformed resistant cells were sensitive to chemical probe (sulforaphane) through inhibition of IL-6/STAT3/NF-κB positive feedback loop whereas parental HER2+ cells did not respond. This data suggests that trastuzumab resistance in HER2+ PTEN− breast cancer induces EMT and subtype switching, which requires unique treatment options. [ABSTRACT FROM AUTHOR]

Reports on the investigation on the obstruction of jellyfish nematocysts by topical agents. Effects of topical application on the skin; Use of scanning electron to study nematocyst discharge on the human cadaver skin; Requirement of standard in vitro test to screen topical agents for protection of human skin.

A letter to the editor is presented in response to the article "Additional Test Evaluating the Psychosocial Status of Psoriasis Patients," that was published in the May 16, 2006 issue.

Despite a dramatic recovery from the brink of extinction, California Condors (Gymnogyps californianus) still face significant anthropogenic threats. Although condor movement patterns across large temporal scales are understood, less is known about their movements on a fine temporal scale. We used a trajectory-based analysis of GPS telemetry data gathered from condors during 2013 to 2018 to investigate the relationship between the distances condors travel in a day, demographic characteristics (e.g., age and sex), and time of year. Most (>71.4%) daily travel distances by condors were <100 km, and, on average, condors traveled 70.1 ± 60.9 km/d (x̄ ± SD). On two occasions one condor traveled >400 km in a single day (477 km one day and 415 km the following day). The tendency for condors to travel long distances increased with age, and condors traveled longer distances during the summer and when nesting. Traveling such long distances likely exposes birds to threats across a greater variety of landscapes than would be expected for birds that moved shorter distances. Given anticipated condor range expansion and population increase, this work highlights the importance of coordinating condor conservation across the broad spatial scales at which they move. [ABSTRACT FROM AUTHOR]

Three common Red Sea soft corals (Cnidaria: Anthozoa), Nephthea sp, Dendronephthya sp and Heteroxenia fuscescens sting humans. Nematocyst venoms of each animal are lethal to mice and hemolytic to human erythrocytes. However, these hemolysins are partially inhibited by known anti-hemolytic agents. Venoms and their gel chromatography-separated fractions have different dermonecrosis and vasopermeability potency in mouse skin. The venom of Heteroxenia fuscescens (Hf) was more lethal (LD50: 0.7 mg/kg), with one prominent 97-kDa protein fraction (LD50: 0.55 mg/kg). Hf venom was more hemolytic, more dermonecrotic, and had more vasopermeable factors than that of the two other species. SDS polyacrylamide gel electrophoresis of soft coral whole venoms and fractions showed different protein molecular masses ranging from 200 to less than 6 kDa. High IgG titers were assayed from venom-sensitized mice blood sera. Enzyme-linked immunosorbent assays (ELISA) marked significant immunological cross-reaction between the studied soft coral venoms and their bioactive fractions. [Copyright &y& Elsevier]

Presents the case of a patient which manifested erythematous, papulovesicular lesions after being stung by Bartholomea annulata. Length of the resolution of the lesions; First aid which was rendered; Discussion on sea anemones.

The polymerase chain reaction (PCR) was used to detect HSV DNA in genomic DNA extracted from skin biopsies obtained from healed skin of five patients with hyperpigmented macules following recurrent cutaneous HSV infections and from eight patients with HSV-associated erythema multiforme (EM). A 92-bp HSV-1 DNA fragment was found in all the skin biopsies from the site of recurrent HSV infection and five of eight (62%) biopsies from the EM patients Virus DNA was not found in tissues distant from the site of HSV recurrence or from a patient without a history of HSV in healed skin from the site of recurrent HSV disease and are consistent with the concept that HSV is involved in EM pathogenesis. [ABSTRACT FROM AUTHOR]

Vertebrates respond to stressful stimuli with the secretion of glucocorticoid (GC) hormones, such as corticosterone (CORT), and measurements of these hormones in wild species can provide insight into physiological responses to environmental and human-induced stressors. California condors (Gymnogyps californianus) are a critically endangered and intensively managed avian species for which information on GC response to stress is lacking. Here we evaluated a commercially available I125 double antibody radioimmunoassay (RIA) and an enzyme-linked immunosorbent assay (ELISA) kit for measurement of CORT and GC metabolites (GCM) in California condor plasma, urate, and feather samples. The precision and accuracy of the RIA assay outperformed the ELISA for CORT and GCM measurements, and CORT and GCM values were not comparable between the two assays for any sample type. RIA measurements of total CORT in condor plasma collected from 41 condors within 15 minutes of a handling stressor were highly variable (median = 70 ng/mL, range = 1–189 ng/mL) and significantly different between wild and captive condors (p = 0.02, two-tailed t-test, n = 10 wild and 11 captive). Urate GCM levels (median = 620 ng/g dry wt., range = 0.74–7200 ng/g dry wt., n = 216) significantly increased within 2 hr of the acute handling stressor (p = 0.032, n = 11 condors, one-tailed paired t-test), while feather section CORT concentrations (median = 18 pg/mm, range = 6.3–68 ng/g, n = 37) also varied widely within and between feathers. Comparison of multiple regression linear models shows condor age as a significant predictors of plasma CORT levels, while age, sex, and plasma CORT levels predicted GCM levels in urates collected within 30 min of the start of handling. Our findings highlight the need for validation when selecting an immunoassay for use with a new species, and suggest that non-invasively collected urates and feathers hold promise for assessing condor responses to acute or chronic environmental and human-induced stressors. [ABSTRACT FROM AUTHOR]

Increasing evidence suggesting breast cancer stem cells (BCSCs) drive metastasis and evade traditional therapies underscores a critical need to exploit the untapped potential of nanotechnology to develop innovative therapies that will significantly improve patient survival. Photothermal therapy (PTT) to induce localized hyperthermia is one of few nanoparticle-based treatments to enter clinical trials in human cancer patients, and has recently gained attention for its ability to induce a systemic immune response targeting distal cancer cells in mouse models. Here, we first conduct classic cancer stem cell (CSC) assays, both in vitro and in immune-compromised mice, to demonstrate that PTT mediated by highly crystallized iron oxide nanoparticles effectively eliminates BCSCs in translational models of triple negative breast cancer. PTT in vitro preferentially targets epithelial-like ALDH + BCSCs, followed by mesenchymal-like CD44+/CD24- BCSCs, compared to bulk cancer cells. PTT inhibits BCSC self-renewal through reduction of mammosphere formation in primary and secondary generations. Secondary implantation in NOD/SCID mice reveals the ability of PTT to impede BCSC-driven tumor formation. Next, we explore the translational potential of PTT using metastatic and immune-competent mouse models. PTT to inhibit BCSCs significantly reduces metastasis to the lung and lymph nodes. In immune-competent BALB/c mice, PTT effectively eliminates ALDH + BCSCs. These results suggest the feasibility of incorporating PTT into standard clinical treatments such as surgery to enhance BCSC destruction and inhibit metastasis, and the potential of such combination therapy to improve long-term survival in patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Single crystals of Pr2Fe4-xCoxSb5 (1 < x < 2.5) were grown from a Bi flux and characterized by X-ray diffraction. The compounds adopt the La2Fe4Sb5 structure type (I4/mmm). The structure of Pr2Fe4-xCoxSb5 (1 < x < 2.5) contains a network of transition metals forming isosceles triangles. The x ∼ 1 analogue is metallic and exhibits a magnetic transition at T1 ≈ 25 K. The magnetic moment obtained from the Curie-Weiss fit is 11.49(4) μB, which is larger than the spin-only Pr3+ moment. The x ∼ 2 analogue orders magnetically at T1 ≈ 80 and T2 ≈ 45 K. This is the first case of the substitution of Co into the La2Fe4Sb5 structure type, evidenced by the increased concentration of dopant with decreased lattice parameters coupled with a change in the transition temperature with a change in the cobalt concentration. The added complexity in the magnetic behavior of the x ∼ 1 and 2 analogues indicates that the increased concentration of Co invokes an additional magnetic contribution of the transition metal in the sublattice. Furthermore, X-ray photoelectron spectroscopy measurements support the change in the oxidation states of transition metals with increasing cobalt concentration. [ABSTRACT FROM AUTHOR]

Describes a case of cutaneous sarcoidosis, a systemic granulomatous disease, of the scrotum. Case background; Eczematous eruption of the scrotum with associated edema and tenderness; Treatment options.

Lead poisoning is preventing the recovery of the critically endangered California condor ( Gymnogyps californianus ) and lead isotope analyses have demonstrated that ingestion of spent lead ammunition is the principal source of lead poisoning in condors. Over an 8 month period in 2009, three lead-poisoned condors were independently presented with birdshot embedded in their tissues, evidencing they had been shot. No information connecting these illegal shooting events existed and the timing of the shooting(s) was unknown. Using lead concentration and stable lead isotope analyses of feathers, blood, and recovered birdshot, we observed that: i) lead isotope ratios of embedded shot from all three birds were measurably indistinguishable from each other, suggesting a common source; ii) lead exposure histories re-constructed from feather analysis suggested that the shooting(s) occurred within the same timeframe; and iii) two of the three condors were lead poisoned from a lead source isotopically indistinguishable from the embedded birdshot, implicating ingestion of this type of birdshot as the source of poisoning. One of the condors was subsequently lead poisoned the following year from ingestion of a lead buckshot (blood lead 556 µg/dL), illustrating that ingested shot possess a substantially greater lead poisoning risk compared to embedded shot retained in tissue (blood lead ~20 µg/dL). To our knowledge, this is the first study to use lead isotopes as a tool to retrospectively link wildlife shooting events. [ABSTRACT FROM AUTHOR]

Presents a case study of fulminant hepatic failure due to a sea anemone sting in a 28-year-old male. Medical history of the patient; Details on the hepatitis serologic tests performed on the patient; Cause of death of the patient.

Hsp90 requires cochaperone Cdc37 to load its clients to the Hsp90 superchaperone complex. The purpose of this study was to utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence to study the full-length human Hsp90-Cdc37 complex and to identity critical residues and their contributions for Hsp90/ Cdc37 interaction in living cells. SRL-PFAC showed that full-length human Hsp90/Cdc37 interaction restored dramatically high luciferase activity through Hsp90-Cdc37-assisted complementation of the N and C termini of luciferase (compared with the set of controls). Immunoprecipitation confirmed that the expressed fusion proteins (NRL-Hsp90 and Cdc37-CRL) preserved their ability to interact with each other and also with native Hsp90 or Cdc37. Molecular dynamic simulation revealed several critical residues in the two interaction patches (hydrophobic and polar) at the interface of Hsp90/Cdc37. Mutagenesis confirmed the critical residues for Hsp90-Cdc37 complex formation. SRL-PFAC bioluminescence evaluated the contributions of these critical residues in Hsp90/Cdc37 interaction. The results showed that mutations in Hsp90 (Q133A, F134A, and A121N) and mutations in Cdc37 (M164A, R167A, L205A, and Q208A) reduced the HspgO/Cdc37 interaction by 70-95% as measured by the resorted luciferase activity through Hsp90-Cdc37-assisted complementation. In comparison, mutations in Hsp90 (E47A and S113A) and a mutation in Cdc37 (A204E) decreased the Hsp90/Cdc37 interaction by 50%. In contrast, mutations of Hsp90 (R46A, SSOA, C481A, and C598A) and mutations in Cdc37 (C54S, C57S, and C64S) did not change Hsp90/Cdc37 interactions. The data suggest that single amino acid mutation in the interface of Hsp90/Cdc37 is sufficient to disrupt its interaction, although Hsp90/Cdc37 interactions are through large regions of hydrophobic and polar interactions. These findings provides a rationale to develop inhibitors for disruption of the Hsp90/Cdc37 interaction. [ABSTRACT FROM AUTHOR]

Anticancer nanomedicines are designed to improve anticancer efficacy by increasing drug accumulation in tumors through enhanced permeability retention (EPR) effect, and to reduce toxicity by decreasing drug accumulation in normal organs through long systemic circulation. However, the inconsistent efficacy/safety of nanomedicines in cancer patients versus preclinical cancer models have provoked debate for nanomedicine design criteria. In this study, we investigate nanomedicine design criteria in three types of preclinical cancer models using five clinically used nanomedicines, which identifies the factors for better clinical translations of their observed clinical efficacy/safety compared to free drug or clinical micelle formulation. When those nanomedicines were compared with drug solution or clinical micelle formulation in breast tumors, long and short-circulating nanomedicines did not enhance tumor accumulation by EPR effect in transgenic spontaneous breast cancer model regardless of their size or composition, although they improved tumor accumulations in subcutaneous and orthotopic breast cancer models. However, when tumors were compared to normal breast tissue, nanomedicines, drug solution and clinical micelle formulation showed enhanced tumor accumulation regardless of the breast cancer models. In addition, long-circulating nanomedicines did not further increase tumor accumulation in transgenic mouse spontaneous breast cancer nor universally decrease drug accumulations in normal organs; they decreased or increased accumulation in different organs, potentially changing the clinical efficacy/safety. In contrast, short-circulating nanomedicines decreased blood concentration and altered drug distribution in normal organs, which are correlated with their clinical efficacy/safety. A reappraisal of current nanomedicine design criteria is needed to ensure consistent clinical translation for improvement of their clinical efficacy/safety in cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I–VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75μg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12μg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1μg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (≤10kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects. [Copyright &y& Elsevier]

Chrysaora quinquecirrha (sea nettle) nematocyst venom is lethal to rainbow killifish (Adina xenica) when injected intraperitoneally or topically applied to the exposed brain or denuded epithelium. The lethal activity is thermostable requiring 100°C heat for inactivation. This paper reports here for the first time that the venom also activates the complement system with the subsequent formation of the C5b-9 terminal complement complex. The events are associated with both a strong chemoattractant release and the tissue damage. These are also, at least in part, responsible for the pathogenesis of some clinical signs and symptoms associated to the jellyfish stings. [Copyright &y& Elsevier]

Summary The herpes simplex virus large subunit of ribonucleotide reductase differs from its counterparts in eukaryotic and prokaryotic cells and in other viruses in that it contains a unique domain that codes for a distinct serine-threonine protein kinase that activates the Ras/MEK/MAPK mitogenic pathway and is required for virus growth. Previous studies suggested that ribonucleotide reductase protein kinase was co-opted from a cellular gene. Cellular genes similar to ribonucleotide reductase protein kinase were not cloned, however, and their function is unknown. Here we report that a novel gene (H11) that codes for a protein similar to herpes simplex virus 2 ribonucleotide reductase protein kinase, is expressed in skin tissues, cultured keratinocytes, and the keratinocyte cell line A431. The protein is phosphorylated and it associates with the plasma membrane. H11 is expressed in keratinocytes with long-term in vitro growth potential and is coexpressed with high levels of adhesion molecules involved in signal transduction, such as β1 integrin. Antisense oligonucleotides that inhibit H11 expression inhibit DNA synthesis and keratinocyte proliferation, suggesting that H11 expression is required for cell growth. [ABSTRACT FROM AUTHOR]

Erythema multiforme follows administration of several drugs or infection with various agents, including herpes simplex virus, a syndrome designated herpes simplex virus associated erythema multiforme. Lesional skin from 21 of 26 (81%) herpes simplex virus associated erythema multiforme patients was positive for herpes simplex virus gene expression as evidenced by reverse transcriptase–polymerase chain reaction with primers for DNA polymerase and/or immunohistochemistry with DNA polymerase antibody. Reverse transcriptase–polymerase chain reaction and immunohistochemistry studies indicated that herpes simplex virus associated erythema multiforme lesional skin from 16 of 21 (76%) DNA polymerase positive herpes simplex virus associated erythema multiforme patients was also positive for interferon-γ, a product of T cells involved in delayed-type hypersensitivity (p < 0.0001 by Pearson correlation coefficient). Interferon-γ signals were in infiltrating mononuclear cells and in intercellular spaces within inflammatory sites in the epidermis and at the epidermis/dermis junction. Herpes simplex virus lesional skin was also positive for DNA polymerase [five of five (100%)] and interferon-γ [four of five (80%)], but lesional skin from drug-induced erythema multiforme patients was negative. Lesional herpes simplex virus associated erythema multiforme keratinocytes also stained with antibody to transforming growth factor-β [14 of 23 (61%)] and cyclin-dependent kinase inhibitor waf [12 of 18 (67%)]. Staining was also seen in keratinocytes from herpes simplex virus lesions [five of five (100%)], but not in normal skin. By contrast, staining with antibody to tumor necrosis factor-α, another pro-inflammatory cytokine, was seen in seven of 11 (64%) drug-induced erythema multiforme patients, but not in herpes simplex virus or herpes simplex virus associated erythema multiforme patients, and lesional keratinocytes from drug-induced ... [ABSTRACT FROM AUTHOR]