Letters, hitherto unpublished, written by members of Sir Walter Scott's family to their old governess.

"Of the forty-seven letters [to Miss Millar] twenty-eight were written by Charlotte Sophia Scott ... twelve by Anne Scott."

Dorothea Scott, otherwise Gotherson and Hogben, of Egerton house, Kent, 1611-1680.

A discourse of polletique and civill honor by Thomas Scott: p. [145]-198.

The genealogy of the Scott and Galloway families, Scotland, Mifflin county, Pennsylvania [and] Bourbon county, Kentucky.

Mode of access: Internet.

Monros of Auchinbowie and cognate families.

Mode of access: Internet.

A true history of several honourable families of the right honourable name of Scot, in the shires of Roxburgh and Selkirk and others adjacent : gathered out of ancient chronicles, histories, and traditions of our fathers /

No. 112 of 240 copies printed.

Contemporary issues in Australian family law: Do we need a more unified and interventionist judicial model

Recent decisions of the Family Court of Australian reflect concerns over the adversarial nature of the legal process. The processes and procedures of the judicial system militate against a detailed examination of the issues and rights of the parties in dispute. The limitations of the family law framework are particularly demonstrated in disputes over the custody of children where the Court has tended to neglect the rights and interests of the primary carer. An alternative "unified family court" framework will be examined in which the Court pursues a more active and interventionist approach in the determination of family law disputes.

“I would have lost the respect of my friends and family if they knew I had bent the road rules” : parents, peers, and the perilous behaviour of young drivers

Young novice drivers are at considerable risk of injury on the road. Their behaviour appears vulnerable to the social influence of their parents and friends. The nature and mechanisms of parent and peer influence on young novice driver (16–25 years) behaviour was explored via small group interviews (n = 21) and two surveys (n1 = 1170, n2 = 390) to inform more effective young driver countermeasures. Parental and peer influence occurred in preLicence, Learner, and Provisional (intermediate) periods. Pre-Licence and unsupervised Learner drivers reported their parents were less likely to punish risky driving (e.g., speeding). These drivers were more likely to imitate their parents and reported their parents were also risky drivers. Young novice drivers who experienced or expected social punishments from peers, including ‘being told off’ for risky driving, reported less riskiness. Conversely drivers who experienced or expected social rewards such as being ‘cheered on’ by friends – who were also more risky drivers – reported more risky driving including crashes and offences. Interventions enhancing positive influence and curtailing negative influence may improve road safety outcomes not only for young novice drivers, but for all persons who share the road with them. Parent-specific interventions warrant further development and evaluation including: modelling safe driving behaviour by parents; active monitoring of driving during novice licensure; and sharing the family vehicle during the intermediate phase. Peer-targeted interventions including modelling of safe driving behaviour and attitudes; minimisation of social reinforcement and promotion of social sanctions for risky driving also need further development and evaluation.

The DUB/USP17 deubiquitinating enzymes: A gene family within a tandemly repeated sequence, is also embedded within the copy number variable Beta-defensin cluste

Background: The DUB/USP17 subfamily of deubiquitinating enzymes were originally identified as immediate early genes induced in response to cytokine stimulation in mice (DUB-1, DUB-1A, DUB-2, DUB-2A). Subsequently we have identified a number of human family members and shown that one of these (DUB-3) is also cytokine inducible. We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the 'CAAX' box protease RCE1.

Results: Here we demonstrate that the human DUB/USP17 family members are found on both chromosome 4p16.1, within a block of tandem repeats, and on chromosome 8p23.1, embedded within the copy number variable betadefensin cluster. In addition, we show that the multiple genes observed in humans and other distantly related mammals have arisen due to the independent expansion of an ancestral sequence within each species. However, it is also apparent when sequences from humans and the more closely related chimpanzee are compared, that duplication events have taken place prior to these species separating.

Conclusions: The observation that the DUB/USP17 genes, which can influence cell growth and survival, have evolved from an unstable ancestral sequence which has undergone multiple and varied duplications in the species examined marks this as a unique family. In addition, their presence within the beta-defensin repeat raises the question whether they may contribute to the influence of this repeat on immune related conditions.

Inhibition of Secretion of Interleukin (IL)-12/IL-23 Family Cytokines by 4-Trifluoromethyl-celecoxib Is Coupled to Degradation via the Endoplasmic Reticulum Stress Protein HERP

Interleukin-12 (IL-12), p80, and IL-23 are structurally related cytokines sharing a p40 subunit. We have recently demonstrated that celecoxib and its COX-2-independent analogue 4-trifluoromethyl-celecoxib (TFM-C) inhibit secretion but not transcription of IL-12 (p35/p40) and p80 (p40/p40). This is associated with a mechanism involving altered cytokine-chaperone interaction in the endoplasmic reticulum (ER). In the present study, we found that celecoxib and TFM-C also block secretion of IL-23 (p40/p19 heterodimers). Given the putative ER-centric mode of these compounds, we performed a comprehensive RTPCR analysis of 23 ER-resident chaperones/foldases and associated co-factors. This revealed that TFM-C induced 1.5-3-fold transcriptional up-regulation of calreticulin, GRP78, GRP94, GRP170, ERp72, ERp57, ERdj4, and ERp29. However, more significantly, a 7-fold up-regulation of homocysteine-inducible ER protein (HERP) was observed. HERP is part of a high molecular mass protein complex involved in ER-associated protein degradation (ERAD). Using co-immunoprecipitation assays, we show that TFM-C induces protein interaction of p80 and IL-23 with HERP. Both HERP siRNA knockdown and HERP overexpression coupled to cycloheximide chase assays revealed that HERP is necessary for degradation of intracellularly retained p80 by TFM-C. Thus, our data suggest that targeting cytokine folding in the ER by small molecule drugs could be therapeutically exploited to alleviate in appropriate inflammation in autoimmune conditions.

SLPI and elafin: multifunctional antiproteases of the WFDC family

SLPI (secretory leucoprotease inhibitor) and elafin represent the archetypal members of the WFDC [WAP (whey acidic protein) four disulfide core] family of proteins, and were originally characterized as protease inhibitors but have since been shown to possess a wider repertoire of activities. These functions include antimicrobial and immunomodulatory properties, suggesting that these proteins may play key roles in the innate immune response, and indicate the potential to develop some of these proteins as novel therapeutics. Susceptibility to host and bacterial protease cleavage may, however, limit the efficacy of recombinant protein therapies in diseases with a high protease burden such as CF (cystic fibrosis) lung disease. To overcome this problem, further refinement of the native proteins will be required to provide effective treatment strategies.

The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention.

Wellness and balance: perceptions amongst female health care professionals negotiating career, family, and continuing education /

The purpose ofthis study was to explore the perceptions of wellness and bidance amongst female health care professionals negotiating career, family aiul continuing education commitments. Five women who met the criteria of having a family (with children), holding a full-time professional career in health care, and who were presently pursuing continuing education were interviewed. This paper begins with the introduction to the topic of research and the questions to be answered. The review of literature explores the theory and research A^ch precede this study and addresses the surrounding areas of: wellness, balance, multiple roles, stress and continuing education. < This study has assumed a qualitative, phenomenological approach. The data collected through the use of individual interviews were analyzed using a two-part process. Analysis using both (a) methodological interpretation and (b) The Listening Guide method has allowed for the uncovering of major themes, and the portrayal of each participant's unique experience. Some of the major themes which emerged from this research include: wellness as multidimensional and fluctuating, making personal sacrifices, the presence of stress, professional as a vital role, and continuing education as something for me. Perhaps the most significant finding this research has identified is the positive role continuing education can hold in the lives of women already negotiating multiple commitments. The notion that continuing education can act as a means of enhancing perceptions of wellness and balance holds a number of implications in theory, practice, and for future research.

Demonstrating distinction at ‘the lowest edge of the black-coated class’: the family expenditures of Edwardian railway clerks

Families at the bottom end of the Edwardian white-collar income spectrum demonstrated middle-class status through observable consumption, at the cost of squeezing other expenditures, including ‘necessities’. This had negative economic impacts, lowering living standards due to inefficiently high budget shares for positional goods. Drawing on the work of Pierre Bourdieu, we examine how railway clerks sought to demonstrate ‘distinction’ from manual workers through certain conspicuous expenditures and how this strategy was progressively undermined by falling real incomes over the Edwardian period.

Contributions to the taxonomy of the Normanellidae (Copepoda, Harpacticoida): description of a new genus from the Brazilian continental shelf and re-assignment of Pseudocletodes vararensis Scott & Scott, 1893 (ex Nannopodidae)

A new genus and species of Normanellidae (Copepoda, Harpacticoida), Paranaiara inajae gen. et sp. nov., is described from the continental shelf off the northern coast of Sao Paulo State, Brazil. The new genus differs from the type genus Normanella Brady, 1880 and Sagamiella Lee & Huys, 1999 in its presence of lamelliform caudal rami, a maxillulary endopod represented by 2 setae, an unarmed maxillipedal syncoxa, and reduced setation on P2 enp-2 (without outer spine) and P3 enp-2 (with only 2 inner setae). All these apomorphic character states are shared with the genus Pseudocletodes Scott & Scott, 1893, formerly placed in the family Nannopodidae (ex Huntemanniidae) and here assigned to the Normanellidae. Pseudocletodes can be differentiated from Paranaiara by the loss of the P1 endopod and of the inner seta on P2-P4 enp-1, the presence of only 2 inner setae on P2 enp-2 (instead of 3) and only 1 inner seta on P4 exp-3 (instead of 2), the presence of a second inner seta on P4 enp-2 (instead of 1), the morphology of the fifth pair of legs which are not medially fused and have only 3 endopodal elements (instead of 4) in the male, and the well developed caudal ramus seta V (instead of rudimentary). It is postulated that prehensility of the P1 endopod was secondarily lost in the common ancestor of Paranaiara and Pseudocletodes. An updated family diagnosis of the Normanellidae and a dichotomous identification key to the 22 currently valid species are presented.

Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1

Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved alpha-helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation.