Crystal structures of a family of layered coordination polymers containing divalent metal ions (Mn2+, Co2+, Ni2+ and Zn2+) and the 3-amino 4-methyl benzoate ion

Peer reviewed

Crystal structures of a family of layered coordination polymers containing divalent metal ions (Mn2+, Co2+, Ni2+ and Zn2+) and the 3-amino 4-methyl benzoate ion

Peer reviewed

Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20–32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD– and the sequence motifs –VALGAVSK– or –GKAAL(N/G/S) (V/A)V– in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77 μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3–fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11 μM). CZS-1 reached 100% haemolysis at 120.87 μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use.

Proficiency and mechanisms of perturbation of mature T-cell homeostasis by the TCL1 family of oncogenes

In the first part of this thesis, the oncogenic potential of TCL1A family genes was comparatively evaluated by using gamma-retroviral vectors to introduce human TCL1A, MTCP1, and TML1 into hematopoietic stem cells/hematopoietic progenitor cells (HSC/HPC) of wild type mice that were transplanted into wild type recipients. TCL1A and MTCP1 recipient mice predominantly developed B-cell malignancies after a median survival of 388 days and 394 days, respectively. The presented data indicates that TCL1A and MTCP1 are oncogenes with comparable oncogenic potential and shows for the first time that MTCP1 is not only a T-cell oncogene, but is able to transform B cells as well. The third family member TML1 induced the development of immature T-cell malignancies in only a few mice. This study provides first evidence for its oncogenic function. Additionally, the transforming potential of compartment-targeted TCL1A variants was evaluated by retroviral expression of a membrane localizing myristoylated (myr-TCL1A) and a nuclear localizing (nls-TCL1A) variant. Recipients of HSC/HPC transduced with myr-TCL1A and nls-TCL1A predominantly developed B-cell malignancies after a median survival of 360 days and 349 days, respectively. There was a significantly shorter latency period for nls-TCL1A compared to the previously described generic TCL1A. Gene expression analysis revealed higher similarities between expression profiles of tumors induced by TCL1A and nls-TCL1A. Together these data implicate that TCL1A’s predominant oncogenic function might rely on its nuclear presence. The second part of this thesis aims to understand if and how TCR stimulation affects the transforming potential of TCL1A. Mature OT-1 T cells carrying monoclonal TCR’s that specifically recognize ovalbumin (OVA) were retrovirally transduced with TCL1A and repeatedly stimulated in vivo with OVA-peptides. TCR stimulated recipient mice of TCL1A transduced T cells showed a significantly accelerated leukemic outgrowth and a reduced median survival of 305 days, when compared to unstimulated recipients (417 days). These data strongly implicate a pro-leukemogenic cooperation of TCL1A and TCR signals that might be actionable in upcoming interventional designs.

Bis(arylene-ethynylene)-s-tetrazines: A Promising Family of n-Type Organic Semiconductors?

We theoretically describe in this work the n-type semiconducting behavior of a set of bis(arylene-ethynylene)-s-tetrazines ((ArCC)2Tz), by comparing their electronic properties with those of their parent diaryl-s-tetrazines (Ar2Tz) after the introduction of ethynylene bridges. The significantly reduced internal reorganization energy for electron transfer is ascribed to an extended delocalization of the LUMO for (ArCC)2Tz as opposite to that for Ar2Tz, which was described mostly localized on the s-tetrazine ring. The largest electronic coupling and the corresponding electron transfer rates found for bis(phenyl-ethynylene)-s-tetrazine, as well as for some halogenated derivatives, are comparable to those reported for the best performing n-type organic semiconductor materials such as diimides and perylenes. The theoretical mobilities for the studied compounds turn out to be in the range 0.3–1.3 cm2 V–1 s–1, close to values experimentally determined for common n-type organic semiconductors used in real devices. In addition, ohmic contacts can be expected when these compounds are coupled to metallic cathodes such as Na, Ca, and Sm. For these reasons, the future application of semiconducting bis(phenyl-ethynylene)-s-tetrazine and its fluorinated and brominated derivatives in optoelectronic devices is envisioned.

Receptor activity-modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors

The calcitonin gene-related peptide (CGRP) family of G protein- coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in aGαs-mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gαs and Gαq but also identify a Gαi component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMPdependent signaling bias among the Gαs, Gαi, and Gαq/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology.

The actinin family of actin crosslinking proteins: natural functions and potential applications in synthetic biology

Actinin and spectrin proteins are members of the Spectrin Family of Actin Crosslinking Proteins. The importance of these proteins in the cytoskeleton is demonstrated by the fact that they are common targets for disease causing mutations. In their most prominent roles, actinin and spectrin are responsible for stabilising and maintaining the muscle architecture during contraction, and providing shape and elasticity to the red blood cell in circulation, respectively. To carry out such roles, actinin and spectrin must possess important mechanical and physical properties. These attributes are desirable when choosing a building block for protein-based nanoconstruction. In this study, I assess the contribution of several disease-associated mutations in the actinin-1 actin binding domain that have recently been linked to a rare platelet disorder, congenital macrothrombocytopenia. I investigate the suitability of both actinin and spectrin proteins as potential building blocks for nanoscale structures, and I evaluate a fusion-based assembly strategy to bring about self-assembly of protein nanostructures. I report that the actinin-1 mutant proteins display increased actin binding compared to WT actinin-1 proteins. I find that both actinin and spectrin proteins exhibit enormous potential as nano-building blocks in terms of their stability and ability to self-assemble, and I successfully design and create homodimeric and heterodimeric bivalent building blocks using the fusion-based assembly strategy. Overall, this study has gathered helpful information that will contribute to furthering the advancement of actinin and spectrin knowledge in terms of their natural functions, and potential unnatural functions in protein nanotechnology.

Catalogo di opere ebraiche greche latine et italiane stampate dai celebri tipografi Soncini ne' secoli XV e XVI, compilato da Gaetano Zaccaria Antonucci prete ravennate.

"Edizione di soli 150 esemplari."

Annales de l'imprimerie des Alde,

Engraved book plates reading. Friederici Nicolai et Amicorum.

A Summary of Archaeological Excavations from 1983-1986 at the Green Family Print Shop, 18AP29, Annapolis, Maryland

18AP29, the Green Family Printshop, also known as the Jonas Green site, was excavated from 1983 to 1986 by Archaeology in Annapolis and Historic Annapolis Foundation. The site is not only the home of a significant figure in colonial Maryland but is also the location of one of the first colonial printing operations in Maryland. This site represents an important pre-industrial business in Annapolis. While this domestic site is complicated and rich, one of the most fascinating aspect of 18AP29 is the discovery of a large quantity of printers' type. Extensive analysis of the printers' type and documentary research on one of the print shop's products, the colonial newspaper, the Maryland Gazette, provides insights into the print culture which was developing during the 18th and 19th centuries. This report summarizes the stratigraphic analysis, minimum vessel counts, and faunal analysis. It provides some description of the printers' type.

Thai family support (TFS) : working with families of young substance users in primary health care

Living with substance users negatively impacts upon family members in many ways, and distress is common. Despite these deep and wide-ranging impacts, supportive interventions for family members in their own right are rarely available. Thailand has substantial and growing problems with substance use, and there is very little support or family members of drug users, especially in community setting. The Thai Family Support (TFS) program was designed for implementation in primary health care units (PCUs) in Thailand. TFS was based on two approaches with existing empirical support in Western contexts—the 5-step method and CRAFT—with adaptations to a Thai setting that included integration with Buddhist practices. Its aims were to increase well-being of family members, reduce mental distress, improve family relationships between family members, and engage substance users in behaviour change. A small-scale randomised controlled trial on TFS with a Delayed Treatment control was conducted, with assessments at 8 weeks (Post 1) and 20-24 weeks (Post 2). Structured interviews with participants and PCU staff and an examination of five case studies augmented the quantitative results. Mixed Model Analyses were applied to quantitative outcomes, and thematic analysis was used for qualitative data. Thirty-six participants (18 in each of Immediate and Delayed Conditions) were recruited. A significant difference at Baseline between the two conditions was observed on the Thai GHQ-28 and Gender, but it was not possible to statistically control for these effects. There was a significant Time by Condition interaction on the Thai GHQ-28, WHOQOL-BREF-THAI and FAS, reflecting greater improvements in the Immediate condition by Post 1, but with the Delayed condition meeting or exceeding that effect by Post 2. On FES Cohesion and Conflict, there were falls across conditions at Post 2, but only Cohesion also showed a Time by Condition interaction, and that effect was consistent with a delayed impact of treatment. Overall, TFS by PCU staff in the Delayed Condition gave similar results to TFS conducted by the researcher, supporting the viability of its dissemination to standard health services. Qualitative data also confirmed the quantitative results. Most participants reported physiological and psychological improvements even though their substance-using relative did not change their drug use behaviour. After completing TFS, participants reported increased knowledge, group support and sharing feeling, having positive patient-professional relationship, having greater knowledge of substance abuse and social support. In particular, they changed their behaviour towards the substance user, resulting in improvements to family relationships. PCU staff gave similar responses on the efficacy of TFS, and saw it as feasible for routine use, although some implementation challenges were identified. The cultural adaptation and in particular the religious activities, were recognised by participants and PCU staff as an important component of TFS to support psychological health and well-being. Findings from this study showed the impact of substance use on family members and difficulties that they experienced when living with the substance users, resulting distresses and burden that may develop severe mental health disease. Drug use policies should be modified to support family members and response to their needs effectively for early prevention. This study also gave preliminary support for application of the TFS program in rural primary care settings and identified some policies that will be required for it to be disseminated more broadly.

A description of the Mei2-like protein family; structure, phylogenetic distribution and biological context

The Schizosaccharomyces pombe Mei2 gene encodes an RNA recognition motif (RRM) protein that stimulates meiosis upon binding a specific non-coding RNA and subsequent accumulation in a “mei2-dot” in the nucleus. We present here the first systematic characterization of the family of proteins with characteristic Mei2-like amino acid sequences. Mei2-like proteins are an ancient eukaryotic protein family with three identifiable RRMs. The C-terminal RRM (RRM3) is unique to Mei2-like proteins and is the most highly conserved of the three RRMs. RRM3 also contains conserved sequence elements at its C-terminus not found in other RRM domains. Single copy Mei2-like genes are present in some fungi, in alveolates such as Paramecium and in the early branching eukaryote Entamoeba histolytica, while plants contain small families of Mei2-like genes. While the C-terminal RRM is highly conserved between plants and fungi, indicating conservation of molecular mechanisms, plant Mei2-like genes have changed biological context to regulate various aspects of developmental pattern formation.

End-of-life care in the intensive care unit : a systematic review of qualitative studies investigating the experiences and perceptions of the patient's family

Review question/objective The review objective is to synthesise the best available evidence on experiences and perceptions of family members of intensive care unit patients on the adequacy of end-of-life care, where life-support modalities have been withheld or withdrawn. Inclusion criteria Types of participants This review will consider studies that report on the experiences and perceptions of patients’ families on EOLC in the ICU, where life-support modalities have been withheld or withdrawn. The family is defined as “those who are closest to the patient... the family may include the biological family, family by acquisition, and the family of choice and friends”. Phenomena of interest The phenomena of interest for this review are the patients’ families experiences, perceptions or views on the adequacy of EOLC delivered in the ICU, where life-support modalities were withheld or withdrawn. These experiences may refer to the following views on domains of care considered important at the end-of-life in the ICU, which have been described already in the existing literature: timely, consistent, and compassionate communication, clinician availability, clinical decision making based on patients’ preferences, goals and values, physical care implemented to maintain patient comfort, holistic interdisciplinary care and bereavement care for families of patients who died.

Superstructures exhibited by oxides of the aurivillius family, (Bi2O2)2+ (Anâ 1BnO3n+1)2â

Bi5Ti3FeO15 and Bi7Ti3Fe3O21 which are n=4 and n=6 members of the family of oxides of the general formula (Bi2O2)2+(An−1BnO3n+1)2− show unusual superstructures, possibly due to cation ordering. Bi5Ti3FeO15; Bi7Ti3Fe3O21; oxides.