The Rain Forests of Home: an Atlas of People and Place

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The Continuing Leverage of Releasing Authorities: Findings from a National Survey

The Robina Institute of Criminal Law and Criminal Justice launched a national survey of releasing authorities in March 2015 to each state, and the U.S. Parole Commission. The importance of the survey was underscored by an endorsement from the Association of Paroling Authorities International (APAI). We are pleased to present the results from this important survey here. This is the first comprehensive survey of parole boards completed in nearly 10 years. Its findings provide a rich database for better understanding the policy and practice of paroling authorities. The last survey to be conducted of paroling authorities was in 2007/2008.The current report offers an expansion and update of previous surveys. The results summarized throughout the report offer a timely resource for paroling authorities, correctional policy-makers and practitioners, legislators, and those with a public policy interest in sentencing and criminal justice operations. It is our hope that the document and its findings provide key justice system and other stakeholders with an incisive snapshot of the work of paroling authorities across the country in a manner that contributes to a larger conversation about sound and effective parole release and revocation practices.The completion of this comprehensive survey and the reporting of its findings offers a timely and invaluable resource for releasing authorities. It provides them and other key justice system stakeholders with a comparative understanding of their colleagues' work across the nation, and contributes to a larger conversation pertaining to effective parole release and revocation practices

Town register: Lincolnville, Northport, Belmont, Morrill, Searsmont and Waldo

The group of towns included in this work are located in the southeastern portion of the county of Waldo, adjacent to the city of Belfast. The region in which they lie is, for the most part hilly and broken, rimmed by low-lying mountains which extend almost to the waters of Penobscot Bay. Portions of the mountain chain extending across the country separate the land into valleys and small plateaus which afford much excellent land for agriculture, the occupation in which most of the inhabitants are engaged. Combining the attractions of seashore and mountain, and abounding in beautiful lakes and streams, this section presents manifold attractions to every lover of the beautiful. These towns are closely connected both from an historical and from a geographical point of view and have a common origin

Engineering of PA-IIL lectin from Pseudomonas aeruginosa – Unravelling the role of the specificity loop for sugar preference

<p>Abstract</p> <p>Background</p> <p>Lectins are proteins of non-immune origin capable of binding saccharide structures with high specificity and affinity. Considering the high encoding capacity of oligosaccharides, this makes lectins important for adhesion and recognition. The present study is devoted to the PA-IIL lectin from <it>Pseudomonas aeruginosa</it>, an opportunistic human pathogen capable of causing lethal complications in cystic fibrosis patients. The lectin may play an important role in the process of virulence, recognizing specific saccharide structures and subsequently allowing the bacteria to adhere to the host cells. It displays high values of affinity towards monosaccharides, especially fucose – a feature caused by unusual binding mode, where two calcium ions participate in the interaction with saccharide. Investigating and understanding the nature of lectin-saccharide interactions holds a great potential of use in the field of drug design, namely the targeting and delivery of active compounds to the proper site of action.</p> <p>Results</p> <p><it>In vitro </it>site-directed mutagenesis of the PA-IIL lectin yielded three single point mutants that were investigated both structurally (by X-ray crystallography) and functionally (by isothermal titration calorimetry). The mutated amino acids (22–23–24 triad) belong to the so-called specificity binding loop responsible for the monosaccharide specificity of the lectin. The mutation of the amino acids resulted in changes to the thermodynamic behaviour of the mutants and subsequently in their relative preference towards monosaccharides. Correlation of the measured data with X-ray structures provided the molecular basis for rationalizing the affinity changes. The mutations either prevent certain interactions to be formed or allow formation of new interactions – both of afore mentioned have strong effects on the saccharide preferences.</p> <p>Conclusion</p> <p>Mutagenesis of amino acids forming the specificity binding loop allowed identification of one amino acid that is crucial for definition of the lectin sugar preference. Altering specificity loop amino acids causes changes in saccharide-binding preferences of lectins derived from PA-IIL, via creation or blocking possible binding interactions. This finding opens a gate towards protein engineering and subsequent protein design to refine the desired binding properties and preferences, an approach that could have strong potential for drug design.</p

Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

BACKGROUND: The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (A(y)) and viable yellow (A(vy)) are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. RESULTS: The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number of liver tumors compared to non-transgenic control mice. CONCLUSIONS: The data demonstrate that liver-specific expression of the agouti gene is not sufficient to induce obesity or diabetes, but, in the absence of these factors, agouti continues to promote hepatocellular carcinogenesis

HDAC3-Dependent Epigenetic Pathway Controls Lung Alveolar Epithelial Cell Remodeling and Spreading via miR-17-92 and TGF-β Signaling Regulation

SummaryThe terminal stages of pulmonary development, called sacculation and alveologenesis, involve both differentiation of distal lung endoderm progenitors and extensive cellular remodeling of the resultant epithelial lineages. These processes are coupled with dramatic expansion of distal airspace and surface area. Despite the importance of these late developmental processes and their relation to neonatal respiratory diseases, little is understood about the molecular and cellular pathways critical for their successful completion. We show that a histone deacetylase 3 (Hdac3)-mediated epigenetic pathway is critical for the proper remodeling and expansion of the distal lung saccules into primitive alveoli. Loss of Hdac3 in the developing lung epithelium leads to a reduction of alveolar type 1 cell spreading and a disruption of lung sacculation. Hdac3 represses miR-17-92 expression, a microRNA cluster that regulates transforming growth factor β (TGF-β) signaling. De-repression of miR-17-92 in Hdac3-deficient lung epithelium results in decreased TGF-β signaling activity. Importantly, inhibition of TGF-β signaling and overexpression of miR-17-92 can phenocopy the defects observed in Hdac3 null lungs. Conversely, loss of miR-17-92 expression rescues many of the defects caused by loss of Hdac3 in the lung. These studies reveal an intricate epigenetic pathway where Hdac3 is required to repress miR-17-92 expression to allow for proper TGF-β signaling during lung sacculation