The works of the Right Reverend Father in God, Ezekiel Hopkins...now first collected.

I. Account of former editions of Bishop Hopkins's works. Account of the present edition. Life of Bishop Hopkins. Critical remarks on the author's writings. The Vanity of the world. A practical exposition on the Lord's prayer. A catechistical exposition on the Lord's prayer. Exposition on the Ten commandments.--II. Discourses on the law. Discourses concerning sin. The doctrine of the two covenants. The doctrine of the two sacraments. The nature and necessity of regeneration.--III. The all-sufficiency of Christ to save sinners. The excellency of heavenly treasures. Practical Christianity, in working out our own salvation. The assurance of heaven and salvation, a powerful motive to serve God with fear. On glorifying God in His attributes. The almost-Christian discovered. On the nature, corruption, and renewing of the conscience. The great duty of mortification.--IV. Death disarmed of its sting; from several considerations. Miscellaneous sermons. Index of texts illustrated.

The works of Ezekiel Hopkins : successively bishop of Raphoe and Derry /

v.1. Memoir of the author, and expositions of the Lord's prayer and the decalogue.--v.2. Discourses concerning sin, the two covenants, the two sacraments and practical religion.--v.3. Death disarmed of its sting and miscellaneous sermons.

Clinical effects of stings by sponges of the genus Tedania and a review of sponge stings worldwide

Contact with sponges (Phylum Porifera) usually results in minimal effects or abrasions, except for species that produce crinitoxins and can cause irritation and dermatitis. There are few reports of sponge stings, mainly in divers or collectors. We report a group of sponge stings from handling flame red/orange sponges on the beach, confirmed to be Tedania anhelans in five cases. All seven patients suffered immediate effects ranging from mild to severe pain, and local inflammation. A 38-year-old female and three children had delayed skin involvement including itchiness, pain, swelling and redness. Blistering and desquamation occurred in the female adult and limited desquamation in one child. Similar delayed effects have been reported in Tedania spp. stings previously. (c) 2005 Elsevier Ltd. All rights reserved.

Logics of marginalisation in health and social care reform:integration, choice, and provider-blind provision

The period 2010–2013 was a time of far-reaching structural reforms of the National Health Service in England. Of particular interest in this paper is the way in which radical critiques of the reform process were marginalised by pragmatic concerns about how to maintain the market-competition thrust of the reforms while avoiding potential fragmentation. We draw on the Essex school of political discourse theory and develop a ‘nodal’ analytical framework to argue that widespread and repeated appeals to a narrative of choice-based integrated care served to take the fragmentation ‘sting’ out of radical critiques of the pro-competition reform process. This served to marginalise alternative visions of health and social care, and to pre-empt the contestation of a key norm in the provision of health care that is closely associated with the notions of ‘any willing provider’ and ‘any qualified provider’: provider-blind provision.

Temporal differences across a bio-geographical boundary reveal slow response of sub-littoral benthos to climate change

The English Channel is located at the biogeographical boundary between the northern Boreal and southern Lusitanian biozones and therefore represents an important area to study the effects of global warming on marine organisms. While the consequences of climatic change in the western English Channel have been relatively well documented for fish, plankton and inter-tidal benthic communities, data highlighting the same effects on the distribution of sub-littoral benthic organisms does, to date, not exist. The present study resurveyed a subset of sites originally surveyed from 1958 to 1959 along the UK coast of the English Channel. The main aims of this resurvey were to describe the present status of benthic communities and to investigate potential temporal changes, in particular distributional changes in western stenothermal ‘cold’ water and southern Lusitanian ‘warm’ water species. The increase in water temperature observed since the historic survey was predicted to have caused a contraction in the distribution of cold water species and an extension in the distribution of warm water species. The temporal comparison did not show any clear broad-scale distributional changes in benthic communities consistent with these predictions. Nevertheless, 2 warm water species, the sting winkle Ocenebra erinacea and the introduced American slipper limpet Crepidula fornicata, did show range extensions and increased occurrence, possibly related to climatic warming. Similarly, warm water species previously not recorded by the historic survey were found. The absence of broad-scale temporal differences in sub-tidal communities in response to climatic warming has been reported for other areas and may indicate that these communities respond far more slowly to environmental changes compared to plankton, fish and inter-tidal organisms.

Temporal differences across a bio-geographical boundary reveal slow response of sub-littoral benthos to climate change

The English Channel is located at the biogeographical boundary between the northern Boreal and southern Lusitanian biozones and therefore represents an important area to study the effects of global warming on marine organisms. While the consequences of climatic change in the western English Channel have been relatively well documented for fish, plankton and inter-tidal benthic communities, data highlighting the same effects on the distribution of sub-littoral benthic organisms does, to date, not exist. The present study resurveyed a subset of sites originally surveyed from 1958 to 1959 along the UK coast of the English Channel. The main aims of this resurvey were to describe the present status of benthic communities and to investigate potential temporal changes, in particular distributional changes in western stenothermal ‘cold’ water and southern Lusitanian ‘warm’ water species. The increase in water temperature observed since the historic survey was predicted to have caused a contraction in the distribution of cold water species and an extension in the distribution of warm water species. The temporal comparison did not show any clear broad-scale distributional changes in benthic communities consistent with these predictions. Nevertheless, 2 warm water species, the sting winkle Ocenebra erinacea and the introduced American slipper limpet Crepidula fornicata, did show range extensions and increased occurrence, possibly related to climatic warming. Similarly, warm water species previously not recorded by the historic survey were found. The absence of broad-scale temporal differences in sub-tidal communities in response to climatic warming has been reported for other areas and may indicate that these communities respond far more slowly to environmental changes compared to plankton, fish and inter-tidal organisms.

Alergia à picada de Himenópteros em cães

Dissertação de Mestrado Integrado em Medicina Veterinária

BIOCHEMICAL VARIABILITY BETWEEN VENOMS FROM DIFFERENT HONEYBEE (APIS-MELLIFERA) RACES

1. The comparison of molecular exclusion cromatography profiles of venoms from sting apparatuses of Apis mellifera ligustica, Apis mellifera adansonii and Africanized honey-bees in Sephadex G-100 revealed both qualitative and quantitative differences.2. The venoms from A.m. ligustica and A.m. adansonii presented, respectively, three and two peaks characteristic of each sub-species, while Africanized honey-bee was characterized by the absence of eight peaks common to the former.3. The polypeptides with M(r) in the range from 100,000 to 7500 da correspond respectively to 62.0%, 66.6% and 68.7% of total proteins from the venon of A.m. ligustica, A.m. adansonii and Africanized honey-bees, while the peptidic fraction with M(r) range from 4100 to 2000 da corresponds to 11.4%, 32.4% and 10.2% of venom protein, respectively.

HIV-1 infection: back and forth between virus and host.

The main obstacles to HIV-1 eradication are linked to the viral ability to evade immune system and establish a reservoir where virus is transcriptionally latent but able to replicate. IFN action and Restriction Factors (RFs) expression, dominant proteins that target multiple steps of the HIV-1 lifecycle, represent an early line of defence Because of their interplay with viral replication, we would like to study the relationship between RFs and the viral amount in latently infected cells.The first part of this project investigates the expression levels variations of a selected group of RFs (APOBEC3G, BST2, TRIM5α, MX2, SAMHD1, SERINC3/5, IFI16 and STING) in HIV-1 patients during the course of infection before and after ART administration by using Real Time qPCR. The second part of this study deals with the role of IFNα and IFNγ, and their role in the immune system disfunction that has been described during chronic inflammation associated to cancer, viral infection such as HIV-1, and autoimmune-disease. Immune Check Point proteins (ICPs) are a group of inhibitory receptors expressed on the cellular surface of immune cells and trigger immunosuppressive signaling pathways leading to T-cell exhaustion and the expression of immune checkpoint molecules (PD-1, PD-L1, TIGIT, LILRB2). The major aim of this project is to assess the clinical meaning of ICPs expression in HIV-1 chronically infected patients to better characterized their involvement in immune system disfunction.

Unbalanced R-loops and micronuclei induced by DNA topoisomerase I poisons in cancer cells

Topoisomerase I (Top1) poisons are among the most clinically-effective drugs used for colon, ovary and lung cancers. Unpublished data from our lab have recently revealed that the structurally-unrelated Top1 poisons, Camptothecin (CPT) and Indimitecan (LMP776), induce the formation of micronuclei (MNi) in human cancer cells. In addition, MNi trigger an innate immune gene response by stimulating the cGAS/STING pathway. As the mechanisms of MNi formation are not fully determined, our aim is here to establish how MNi form after Top1 poisoning. Using immunofluorescence assays and EdU labelling of nascent DNAs, our results show that, after 24 hours of recovery, a short treatment with sub-cytotoxic doses of Top1 poisons induces the formation of MNi that do not contain newly synthetized (EdU+) DNA. We also saw that Top1 poisons delay replication machinery reducing EdU incorporation and produce significant levels of the damage markers γH2AX and p53BP1 in S-phase cells but not in G1 and G2/M cells. The results also show that MNi formation is dependent on R-loops, as RNaseH1 overexpression markedly reduces Top1 induced MNi. Genome-wide mapping of R-loops by DRIP-seq technique revealed that R-loop levels are both decreased and increased by CPT. In particular, increased R-loops are mainly found at active genes and always overlapped with Top1cc sites. We also found that increased R-loops overlap with lamina-associated chromatin domains while decreased R-loops correlate with replication origin sites. Overall, our data are consistent with the formation of MNi due to R-loop increase and under-replication at specific regions caused by Top1 poisons. These results will eventually help in developing new strategies for effective personalized interventions by using Top1-targeted compounds as immuno-modulators in cancer patients.

R-loops and G4-structures: from DNA damage to innate immune response gene activation

Non-B DNA structures like R-loops and G-quadruplexes play a pivotal role in several cellular vital processes like DNA transcription regulation. Misregulation of said non-canonical DNA structures can often lead to genome instability, DNA damage, and, eventually, to the activation of an innate immune response. For such reasons they have been studied as adjuvants in anticancer therapies. Here we studied drugs targeting R-loops (Top1 poisons) and G4s (hydrazone derivatives) in order to observe their effects in terms of DNA damage induction and, subsequently, activation of innate immune response. We studied how non-cytotoxic doses of ampthotecin and LMP-776 impact on genome instability, are capable to induce DNA damage and micronuclei, and, eventually lead to an innate immune gene response via the cGAS/STING pathway. G-quadruplexes are another ubiquitous, non-canonical DNA structure, more abundant in telomeric regions, demonstrating a marked relation with the impairment of telomerase and the regulation of DNA replication and transcription. Furthermore, we investigated the properties of new-synthesized molecules belonging to the highly promising class of hydrazone derivatives, in terms of cytotoxicity, ability to stabilize G4-structures, induce DNA damage, and activate interferon-B production. Both Top1 poisons and G4-stabilizers possess several features that can be very useful in clinical applications, in light of their ability to stimulate innate immune response factors and exert a certain cell-killing power, plus they offer a broad and diverse range of treatment options in order to face a variety of patient treatment needs. It is for these very reasons that it is of uttermost importance that further studies are conducted on these compounds, in order to synthesize new and increasingly powerful and flexible ones, with fewer side effects to customize therapies on specific cancers’ and patients’ features.