Class and comparison: subjective social location and lay experiences of constraint and mobility.

Lay perceptions and experiences of social location have been commonly framed with reference to social class. However, complex responses to, and ambivalence over, class categories have raised interesting analytic questions relating to how sociological concepts are operationalized in empirical research. For example, prior researchers have argued that processes of class dis-identification signify moral unease with the nature of classed inequalities, yet dis-identification may also in part reflect a poor fit between 'social class' as a category and the ways in which people accord meaning to, and evaluate, their related experiences of socio-economic inequality. Differently framed questions about social comparison, aligned more closely with people's own terms of reference, offer an interesting alternative avenue for exploring subjective experiences of inequality. This paper explores some of these questions through an analysis of new empirical data, generated in the context of recession. In the analysis reported here, class identification was common. Nevertheless, whether or not people self identified in class terms, class relevant issues were perceived and described in highly diverse ways, and lay views on class revealed it to be a very aggregated as well as multifaceted construct. It is argued that it enables a particular, not general, perspective on social comparison. The paper therefore goes on to examine how study participants compared themselves with familiar others, identified by themselves. The evidence illuminates social positioning in terms of constraint, agency and (for some) movement, and offers insight into very diverse experiences of inequality, through the comparisons that people made. Their comparisons are situated, and pragmatic, accounts of the material contexts in which people live their lives. Linked evaluations are circumscribed and strongly tied to these proximate material contexts.The paper draws out implications for theorizing lay perspectives on class, and subjective experiences of inequality.

NRAGE mediates p38 activation and neural progenitor apoptosis via the bone morphogenetic protein signaling cascade.

Understanding the molecular events that govern neural progenitor lineage commitment, mitotic arrest, and differentiation into functional progeny are germane to our understanding of neocortical development. Members of the family of bone morphogenetic proteins (BMPs) play pivotal roles in regulating neural differentiation and apoptosis during neurogenesis through combined actions involving Smad and TAK1 activation. We demonstrate that BMP signaling is required for the induction of apoptosis of neural progenitors and that NRAGE is a mandatory component of the signaling cascade. NRAGE possesses the ability to bind and function with the TAK1-TAB1-XIAP complex facilitating the activation of p38. Disruption of NRAGE or any other member of the noncanonical signaling cascaded is sufficient to block p38 activation and thus the proapoptotic signals generated through BMP exposure. The function of NRAGE is independent of Smad signaling, but the introduction of a dominant-negative Smad5 also rescues neural progenitor apoptosis, suggesting that both canonical and noncanonical pathways can converge and regulate BMP-mediated apoptosis. Collectively, these results establish NRAGE as an integral component in BMP signaling and clarify its role during neural progenitor development.

Postnatal development and gender-dependent expression of TIP39 in the rat brain.

Tuberoinfundibular peptide of 39 residues (TIP39) is a selective agonist of the parathyroid hormone 2 (PTH2) receptor. The topographical distributions of TIP39 and the PTH2 receptor in the brain, described for young male rats, suggested that TIP39 has limbic and endocrine functions. In the present study, we investigated the expression of TIP39 and the PTH2 receptor in male and female rat brain during postnatal development by means of in situ hybridization histochemistry, quantitative RT-PCR, and immunocytochemistry. TIP39's distribution and expression levels are similar in young female and male brains. TIP39 mRNA levels peak at postnatal day 14 and subsequently decline both in the subparafascicular area and in the medial paralemniscal nucleus, the two major sites where TIP39 is synthesized. A greater developmental decrease in TIP39 expression in males leads to greater levels in older females than older males. The decrease is partially reversed by prepubertal but not postpubertal gonadectomy. TIP39 peptide levels in cell bodies change in parallel with mRNA levels, whereas TIP39 appears and disappears somewhat later in nerve fibers. In addition, TIP39 peptide levels are also sexually dimorphic in older rats. In contrast, PTH2 receptor expression in the brain does not decrease during puberty and is not sexually dimorphic even in old animals. The appearance of TIP39 during early, and decline during late, postnatal development together with the gender-dependent levels in mature animals suggests that TIP39 may play a role in sexual maturation or gender-specific functions.

Calcitonin gene-related peptide-containing pathways in the rat forebrain.

The present study focuses on the topographical distribution of calcitonin gene-related peptide (CGRP)-containing cell bodies and fibers and their connections and pathways in the rat forebrain. We confirm previously reported CGRP projections from the perifornical area of the hypothalamus to the lateral septum, from the posterior thalamus to the caudate putamen and cerebral cortex, and from the parabrachial nuclei to the central extended amygdala, lateral hypothalamus, and ventromedial thalamus. Despite previous descriptions of CGRP in the central nervous system, important neuroanatomical aspects of the forebrain CGRP system remained obscure, which we addressed by using brain lesion techniques combined with modern immunohistology. We first report CGRP terminal fields in the olfactory-anterior septal region and also CGRP projections from the parabrachial nuclei to the olfactory-anterior septal region, the medial prefrontal cortex, the interstitial nucleus of the anterior commissure, the nucleus of the lateral olfactory tract, the anterior amygdaloid area, the posterolateral cortical amygdaloid nucleus, and the dorsolateral part of the lateral amygdaloid nucleus. In addition, we identified a CGRP cell group in the premamillary nuclei and showed that it projects to the medial CGRP layer of the lateral septum. CGRP fibers usually join other pathways rather than forming bundles. They run along the fornix from the hypothalamus, along the supraoptic decussations or the inferior thalamic peduncle-stria terminalis pathway from the posterior thalamus, and along the superior cerebellar peduncle, thalamic fasciculus, and ansa peduncularis from the parabrachial nuclei. This description of the forebrain CGRP system will facilitate investigation of its role in higher brain functions.

Education and evidence are needed to improve neonatal parenteral nutrition practice.

BACKGROUND: Parenteral nutrition (PN) is an essential component of neonatal care for those infants who are unable to tolerate adequate enteral feeding. Its use is not without complications such as biochemical derangements, sepsis, thrombosis, extravasation of fluid, and death. Such complications can be reduced by meticulous management of PN in response to biochemical abnormalities, nutrition teams, policies to reduce sepsis, and staff training to be more aware of pericardial and pleural effusions. We ascertained the current practices in PN administration and management of complications in all neonatal units with 6 or more intensive care cots in England, Scotland, and Wales. METHODS: Telephone survey of middle grade doctors (Specialist Registrars) working in all 57 neonatal units was conducted using a standard questionnaire. The questions were focused around practical issues and problems that are commonly encountered with PN practice, including composition, complications, and nutrition support. RESULTS: A response was obtained from 95% of the units contacted and a wide range of practices observed. Thirty-three percent of units delay protein (nitrogen) until > 48 hours after birth. Lipid infusions are stopped in proven or suspected sepsis in just over half of all units. In hyperglycemic preterm infants, 25 units decrease their glucose infusion, 21 commence insulin, and 8 have no policy. Two thirds of middle grade doctors had no idea of the amount of protein or nitrogen to prescribe for these infants, and only one-third involve a pharmacist in the PN prescribing. CONCLUSIONS: There is a diverse practice and knowledge with a concerning lack of education in nutrition among the middle grade doctors in England, Scotland, and Wales. The management of common complications such as sepsis and hyperglycemia are highly variable. Improved staff training and production of unified evidence-based guidelines need urgent consideration.

Analytical Validation of a Highly Quantitative, Sensitive, Accurate, and Reproducible Assay (HERmark) for the Measurement of HER2 Total Protein and HER2 Homodimers in FFPE Breast Cancer Tumor Specimens.

We report here the results of the analytical validation of assays that measure HER2 total protein (H2T) and HER2 homodimer (H2D) expression in Formalin Fixed Paraffin Embedded (FFPE) breast cancer tumors as well as cell line controls. The assays are based on the VeraTag technology platform and are commercially available through a central CAP-accredited clinical reference laboratory. The accuracy of H2T measurements spans a broad dynamic range (2-3 logs) as evaluated by comparison with cross-validating technologies. The measurement of H2T expression demonstrates a sensitivity that is approximately 7-10 times greater than conventional immunohistochemistry (IHC) (HercepTest). The HERmark assay is a quantitative assay that sensitively and reproducibly measures continuous H2T and H2D protein expression levels and therefore may have the potential to stratify patients more accurately with respect to response to HER2-targeted therapies than current methods which rely on semiquantitative protein measurements (IHC) or on indirect assessments of gene amplification (FISH).

The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus.

This study reports the distribution of parathyroid hormone 2 receptor (PTH2R)-immunoreactive fibers in the hypothalamus using fluorescent amplification immunocytochemistry. The pattern of immunolabeling is strikingly similar to that of tuberoinfundibular peptide of 39 residues (TIP39), a peptide recently purified from bovine hypothalamus and proposed to be a ligand of the PTH2R based on pharmacological data. To investigate the anatomical basis of suggestions that TIP39 affects the secretion of several hypophysiotropic hormones we performed double-labeling studies and found that only somatostatin fibers contain PTH2R in the median eminence, which suggests that somatostatin release could be directly regulated via the PTH2R. However, several hypothalamic nuclei projecting to the median eminence contain a high density of both TIP39 and PTH2R fibers and terminals. We report here, that the PTH2R terminals also contain vesicular glutamate transporter-2, and suggest that TIP39 terminals are ideally positioned to modulate glutamatergic influences on hypophysiotropic neurons.

Interdependencies, values and the reshaping of difference: gender and generation at the birth of twentieth-century modernity.

The paper explores the mutuality of values, claims and social relations in the process of social change. Values are not separable from social relations but are embedded in the shaping and reshaping of social difference and interdependence. The paper focuses on developments around the turn of the twentieth century, and analyses changes in the relative social positioning of children and adults, and women and men, shifting patterns of interdependence, and linked values and ideas about difference. The reconfiguring of generational and gender relations was integral to the first fertility decline, to transformation in family life and societal divisions of labour, and to the embedding of particular values and claims regarding gendered difference, identities and gender appropriate roles. Analysis of these developments reveals the mutuality of 'cultural' and 'material' processes and holds lessons for interpreting social change today.