A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice.

While most effects of dopamine in the brain are mediated by the D1 and D2 receptor subtypes, other members of this G protein-coupled receptor family have potentially important functions. D3 receptors belong to the D2-like subclass of dopamine receptors, activation of which inhibits adenylyl cyclase. Using targeted mutagenesis in mouse embryonic stem cells, we have generated mice lacking functional D3 receptors. A premature chain-termination mutation was introduced in the D3 receptor gene after residue Arg-148 in the second intracellular loop of the predicted protein sequence. Binding of the dopamine antagonist [125I]iodosulpride to D3 receptors was absent in mice homozygous for the mutation and greatly reduced in heterozygous mice. Behavioral analysis of mutant mice showed that this mutation is associated with hyperactivity in an exploratory test. Homozygous mice lacking D3 receptors display increased locomotor activity and rearing behavior. Mice heterozygous for the D3 receptor mutation show similar, albeit less pronounced, behavioral alterations. Our findings indicate that D3 receptors play an inhibitory role in the control of certain behaviors.

The peptide binding site of the substance P (NK-1) receptor localized by a photoreactive analogue of substance P: presence of a disulfide bond.

Substance P (SP) is a neuropeptide that mediates multiple physiological responses including transmission of painful stimuli and inflammation via an interaction with a receptor of known primary sequence. To identify the regions of the SP receptor, also termed the NK-1 receptor, involved in peptide recognition, we are using analogues of SP containing the photoreactive amino acid p-benzoyl-L-phenylalanine (Bpa). In the present study, we used radioiodinated Bpa8-SP to covalently label with high efficiency the rat SP receptor expressed in a transfected mammalian cell line. To identify the amino acid residue that serves as the site of covalent attachment, a membrane preparation of labeled receptor was subjected to partial enzymatic cleavage by trypsin. A major digestion product of 22 kDa was identified. Upon reduction with 2-mercaptoethanol the mass of this product decreased to 14 kDa. The 22-kDa tryptic fragment was purified in excellent yield by preparative SDS/PAGE under nonreducing conditions. Subcleavage with Staphylococcus aureus V8 protease and endoproteinase ArgC yielded fragments of 8.2 and 9.0 kDa, respectively. Upon reductive cleavage, the V8 protease fragment decreased to 3.0 kDa while the endoproteinase ArgC fragment decreased to 3.2 kDa. Taking into consideration enzyme specificity, molecular size, determination of the presence or absence of N-glycosylation sites, and recognition by antibodies to specific sequences of the SP receptor, the V8 protease fragment is Thr-173 to Glu-183, while the endoproteinase ArgC fragment is Val-178 to Arg-190. These two fragments share the common sequence Val-Val-Cys-Met-Ile-Glu (residues 178-183). The site of covalent attachment of radioiodinated Bpa8-SP is thus restricted to a residue within this overlap sequence. The data presented here also establish that the cysteine residue in this sequence Cys-180, which is positioned in the middle of the second extracellular loop, participates in a disulfide bond that links the first and second extracellular loops of the receptor.

The genetic link between the Chinese bamboo partridge (Bambusicola thoracica) and the chicken and junglefowls of the genus Gallus.

Further comparison of mitochondrial control-region DNA base sequences of 16 avian species belonging to the subfamily Phasianinae revealed the following: (i) Generalized perdicine birds (quails and partridges) are of ancient lineages. Even the closest pair, the common quail (Coturnix coturnix japonica) and the Chinese bamboo partridge (Bambusicola thoracica), maintained only 85.71% identity. (ii) The 12 species of phasianine birds previously and presently studied belonged to three distinct branches. The first branch was made exclusively of members of the genus Gallus, while the second branch was made of pheasants of the genera Phasianus, Chrysolophus, and Syrmaticus. Gallopheasants of the genus Lophura were distant cousins to these pheasants. The great argus (Argusianus argus) and peafowls of the genus Pavo constituted the third branch. The position of peacock-pheasants of the genus Polyplectron in the third branch was similar to that of the genus Lophura in the second branch. Members of the fourth phasianine branch, such as tragopans and monals, were not included in the present study. (iii) The one perdicine species, Bambusicola thoracica, was more closely related to phasianine genera Gallus and Pavo than to members of other perdicine genera. The above might indicate that Bambusicola belong to one-stem perdicine lineage that later splits into two sublineages that yielded phasianine birds, one evolving to Gallus, and the other differentiating toward Pavo and its allies.

The role of the social environment in non-suicidal self-injury among LGBTQ youth: A mixed methods study

Non-suicidal self-injury (NSSI), such as cutting and burning, is a widespread social problem among lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) youth. Extant research indicates that this population is more than twice as likely to engage in NSSI than heterosexual and cisgender (non-transgender) youth. Despite the scope of this social problem, it remains relatively unexamined in the literature. Research on other risk behaviors among LGBTQ youth indicates that experiencing homophobia and transphobia in key social contexts such as families, schools, and peer relationships contributes to health disparities among this group. Consequently, the aims of this study were to examine: (1) the relationship between LGBTQ youth's social environments and their NSSI behavior, and (2) whether/how specific aspects of the social environment contribute to an understanding of NSSI among LGBTQ youth. This study was conducted using an exploratory, sequential mixed methods design with two phases. The first phase of the study involved analysis of transcripts from interviews conducted with 44 LGBTQ youth recruited from a community-based organization. In this phase, five qualitative themes were identified: (1) Violence; (2) Misconceptions, Stigma, and Shame; (3) Negotiating LGBTQ Identity; (4) Invisibility and Isolation; and (5) Peer Relationships. Results from the qualitative phase were used to identify key variables and specify statistical models in the second, quantitative, phase of the study, using secondary data from a survey of 252 LGBTQ youth. The qualitative phase revealed how LGBTQ youth, themselves, described the role of the social environment in their NSSI behavior, while the quantitative phase was used to determine whether the qualitative findings could be used to predict engagement in NSSI among a larger sample of LGBTQ youth. The quantitative analyses found that certain social-environmental factors such as experiencing physical abuse at home, feeling unsafe at school, and greater openness about sexual orientation significantly predicted the likelihood of engaging in NSSI among LGBTQ youth. Furthermore, depression partially mediated the relationships between family physical abuse and NSSI and feeling unsafe at school and NSSI. The qualitative and quantitative results were compared in the interpretation phase to explore areas of convergence and incongruence. Overall, this study's findings indicate that social-environmental factors are salient to understanding NSSI among LGBTQ youth. The particular social contexts in which LGBTQ youth live significantly influence their engagement in this risk behavior. These findings can inform the development of culturally relevant NSSI interventions that address the social realities of LGBTQ youth's lives.

Summary of the evolution of the fortifications of Santa Barbara Castle in Alicante from its origins to the beginning of the eighteenth century

Since ancient times, Alicante has been considered a strategic location on the east coast of Spain. Situated close to the sea, it is protected to the southeast by the Cape of Huerta and to the southwest by the Cape of Santa Pola. The city lies at the foot of Mount Benacantil, a high outcrop which has been the site of defensive buildings since time immemorial due to its naturally strong position: it was undoubtedly one of the strongest natural sites in the Levant. Its summit, lying 160 metres above the sea, is topped by a series of fortified enclosures now known as Santa Barbara Castle. This paper briefly describes the alterations made to the castle fortifications from its origins through the Renaissance, including the Muslim and Christian periods until the late fifteenth century and subsequent alterations to adapt new bastioned fortification techniques, and depicts the status of the fortress in each period. This paper is the result of doctoral research carried out at different national and international archives and leading to a thesis presented in 2011.

Political economy of the Agenda 2010 reforms: How Gerhard Schröder overcame the "blocked republic". ACES Cases No. 2008.3

This essay will show that the Schröder-led government managed to break the political gridlock and introduce the Agenda 2010 because key institutional structures of Germany‟s political economy had lost their obstructive powers. In other words, the formerly semi-sovereign state had reclaimed its sovereignty. To understand how this happened, Peter Katzenstein's concept of the semi-sovereign state is first explored as a framework through which to analyze economic policy continuity and change. Within this framework, the causes for constant reform inertia between 1982 and 2002, in spite of varying political constellations and changes in the country‟s economic structure, are then discussed. This analysis will demonstrate that the Agenda 2010 reforms are predominantly a result of underlying incremental change in the political economy and its effect on the political decision-making process. Finally, the findings of this analysis are summarized and discussed with the aim of better understanding the economic policies of the current grand coalition government of the CDU/CSU and the SPD government under Chancellor Angela Merkel.

Proceedings of the ... annual meeting of the Virginia state bar association.

List of members in each volume; cumulative necrological list, in volumes for 1896- ; obituaries of members in volumes for 1891, 1893, 1895-

Annual report of the State Mine Inspector.

Title varies slightly.

Biennial report of the Board of State Harbor Commissioners for ...

Published: Sacramento : State Office, Supt. State Print, 1882-1941.

Minutes of the ... annual meeting and reunion of the United Confederate Veterans ...

The issue for 1917 has title: Reunion of United Confederate Veterans. Proceedings of the twenty-seventh annual reunion of the Confederate Veterans, the eighteenth annual convention of the Confederate Southern Memorial Association and the twenty-second annual reunion of the Sons of Confederarte Veterans, held in Washington, D. C. June 4, 5, 6 and 7, 1917. Washington, 1918.

Transcript of the Federal Interagency Coordinating Committee on Digital Cartography governmentwide meeting : May 20, 1987, Auditorium U.S. Geological Survey.

"May 20, 1987."

Journal of the Philippine commission : being the inaugural session of the first Philippine Legislature, begun and held at the city of Manila October 16, 1907 [to February 1, 1908].

Included also in the entry for the numbered session.

Complete roster of the Eighth Regiment New Hampshire Volunteers.

Reprinted from the Revised register of the soldiers and sailors of New Hampshire in the war of the rebellion, Concord, 1895.

Papers illustrating the history of the Scots brigade in the service of the United Netherlands, 1572-1782;

Vol. 3 includes half-title: The remebrance, or The progress of a regiment commanded by my Lord Portmore in the year 1701 and 1702 ... giveing a true acount of al ther deeds and quartering the space of the ... by John Scot, souldier.

Annual report of the Commissioner of Labor /

Description based on: 2nd (1902).