Neutral Hydrogen Structures Trace Dust Polarization Angle: Implications for Cosmic Microwave Background Foregrounds.

Using high-resolution data from the Galactic Arecibo L-Band Feed Array HI (GALFA-Hi) survey, we show that linear structure in Galactic neutral hydrogen (Hi) correlates with the magnetic field orientation implied by Planck 353 GHz polarized dust emission. The structure of the neutral interstellar medium is more tightly coupled to the magnetic field than previously known. At high Galactic latitudes, where the Planck data are noise dominated, the Hi data provide an independent constraint on the Galactic magnetic field orientation, and hence the local dust polarization angle. We detect strong cross-correlations between template maps constructed from estimates of dust intensity combined with either Hi-derived angles, starlight polarization angles, or Planck 353 GHz angles. The Hi data thus provide a new tool in the search for inflationary gravitational wave B-mode polarization in the cosmic microwave background, which is currently limited by dust foreground contamination.

Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease.

BACKGROUND: Molecular profiling has identified at least four subtypes of invasive breast carcinoma, which exhibit distinct clinical behaviour. There is good evidence now that DCIS represents the non-obligate precursor to invasive breast cancer and therefore it should be possible to identify similar molecular subtypes at this stage. In addition to a limited five-marker system to identify molecular subtypes in invasive breast cancer, it is evident that other biological molecules may identify distinct tumour subsets, though this has not been formally evaluated in DCIS. METHODS: Tissue microarrays were constructed for 188 cases of DCIS. Immunohistochemistry was performed to examine the expression patterns of oestrogen receptor (ER), progesterone receptor (PR), Her2, EGFR, cytokeratin (CK) 5/6, CK14, CK17, CK18, ß4-integrin, ß6-integrin, p53, SMA, maspin, Bcl-2, topoisomerase IIα and P-cadherin. Hierarchical clustering analysis was undertaken to identify any natural groupings, and the findings were validated in an independent sample series. RESULTS: Each of the intrinsic molecular subtypes described for invasive breast cancer can be identified in DCIS, though there are differences in the relative frequency of subgroups, in particular, the triple negative and basal-like phenotype is very uncommon in DCIS. Hierarchical cluster analysis identified three main subtypes of DCIS determined largely by ER, PR, Her2 and Bcl-2, and this classification is related to conventional prognostic indicators. These subtypes were confirmed in an analysis on independent series of DCIS cases. CONCLUSION: This study indicates that DCIS may be classified in a similar manner to invasive breast cancer, and determining the relative frequency of different subtypes in DCIS and invasive disease may shed light on factors determining disease progression. It also demonstrates a role for Bcl-2 in classifying DCIS, which has recently been identified in invasive breast cancer.

The investigation and management of unilateral nipple discharge.

INTRODUCTION: Between 16,000 and 48,000 women are estimated to present to UK breast clinics with nipple discharge each year. The incidence of malignancy in these women is 2.7-24.2%. Currently, there is no consensus on the best way to investigate and manage these women. The aim of this study was to assess the rate of malignancy in women presenting with unilateral nipple discharge, and to evaluate the role of examination, imaging and cytology in reliably predicting outcome. METHODS: Breast units were asked to prospectively collect data on all new patients with unilateral nipple discharge. Data collected included discharge colour, whether it was uniductal or multiductal, examination and imaging findings, cytology results and outcome. RESULTS: Complete datasets were submitted by 5 units on 228 patients. The incidence of malignancy was 4.4%. Clinical examination was valuable in detecting malignancy and multiductal discharge was not related to malignancy. The positive predictive value for detecting malignancy for an abnormality found on mammography was 53.5% and for ultrasonography, it was 65.2%. The role of cytology in detecting malignancy was inconclusive with positive predictive values of the presence of red blood cells and epithelial cells at 6.1% and 10.7% respectively. CONCLUSIONS: A large number of women are investigated for nipple discharge (with huge resource implications) but there is little reliable evidence on the best way to investigate and manage these patients. A larger study is needed to evaluate the role of investigations in nipple discharge to produce guidelines on optimal management.

Expanding insights into the role of cell proliferation in plant development.

Development in plants relies largely on the activity of meristems, which are regions at the apices of shoots and roots that are capable of prolonged organogenesis. Developmental patterning and morphogenesis in plants is principally determined by post-embryonic regulation of the shoot, root and flower meristems, which enable plants to modify their form rapidly in response to different environmental conditions. Because meristems are continually generating new organs and tissues, they provide excellent model systems in which to study the processes of cell division, differentiation and organ formation. Here, we describe recent studies and several classic experiments that are helping to uncover the mechanisms controlling meristem development and the role of cell division in morphogenesis and patterning in plants.

Determinants for cleavage of the chlorophyll a/b binding protein precursor: a requirement for a basic residue that is not universal for chloroplast imported proteins.

We demonstrate that the precursor of the major light-harvesting chlorophyll a/b binding protein (LHCP of Photosystem II), encoded by a Type I gene, contains distinct determinants for processing at two sites during in vitro import into the chloroplast. Using precursors from both pea and wheat, it is shown that primary site processing, and release of a approximately 26-kD peptide, depends on an amino-proximal basic residue. Substitution of an arginine at position -4 resulted in an 80% reduction in processing, with the concomitant accumulation of a high molecular weight intermediate. Cleavage occurred normally when arginine was changed to lysine. The hypothesis that a basic residue is a general requirement for transit peptide removal was tested. We find that the precursors for the small subunit of Rubisco and Rubisco activase do not require a basic residue within seven amino acids of the cleavage site for maturation. In the wheat LHCP precursor, determinants for efficient cleavage at a secondary site were identified carboxy to the primary site, beyond what is traditionally called the transit peptide, within the sequence ala-lys-ala-lys (residues 38-41). Introduction of this sequence into the pea precursor, which has the residues thr-thr-lys-lys in the corresponding position, converted it to a substrate with an efficiently recognized secondary site. Our results indicate that two different forms of LHCP can be produced with distinct NH2-termini by selective cleavage of a single precursor polypeptide.

CLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase.

The CLAVATA1 (CLV1) and CLAVATA3 (CLV3) proteins form a potential receptor and ligand pair that regulates the balance between cell proliferation and differentiation at the shoot meristem of Arabidopsis. CLV1 encodes a receptor-kinase, and CLV3 encodes a predicted small, secreted polypeptide. We demonstrate that the CLV3 and CLV1 proteins coimmunoprecipitate in vivo, that yeast cells expressing CLV1 and CLV2 bind to CLV3 from plant extracts, and that binding requires CLV1 kinase activity. CLV3 only associates with the presumed active CLV1 protein complex in vivo. More than 75% of CLV3 in cauliflower extracts is bound with CLV1, consistent with hypotheses of ligand sequestration. Soluble CLV3 was found in an approximately 25-kilodalton multimeric complex.

Meristems: start your signaling.

All of the cells of the shoot apex are derived from a small number of stem cells in the center of the shoot meristem. Hence, cell lineage plays no role in establishing pattern formation or cell fate at the shoot apex. Growing evidence has implicated a number of cell signaling pathways in regulating shoot meristem development and organ formation. These signaling pathways include receptor-mediated signaling, protein movement via plasmodesmata, and potential feedback loops.

Effect of adding and removing N-glycosylation recognition sites on the thermostability of barley alpha-glucosidase.

The thermostability of alpha-glucosidase is important because the conversion of starch to fermentable sugars during the industrial production of beer and fuel ethanol typically occurs at relatively high temperatures (60-75 degrees C). Barley (Hordeum vulgare) alpha-glucosidase is unstable at these elevated temperatures; however, the alpha-glucosidase from sugar beet (Beta vulgaris) is stable at these temperatures. An alignment of the deduced amino acid sequences of barley and sugar beet alpha-glucosidases revealed considerable differences in the number and position of N-glycosylation recognition sites (NGRS). Other researchers have shown that additions or removals of NGRS resulted in either the stabilization or destabilization of the enzymes at elevated temperatures. NGRS present in the barley sequence and absent in the sugar beet sequence were removed via site-directed mutagenesis from the barley protein. Recognition sites absent in the barley sequence and present in the sugar beet sequence were added via mutagenesis into the barley alpha-glucosidase. Two mutations significantly increased thermostability, one mutation significantly decreased thermostability and five mutations had little effect on alpha-glucosidase thermostability.

Postnatal alterations of GABA receptor profiles in the rat superior colliculus.

Midbrain sections taken from Sprague-Dawley rats of varying ages within the first four postnatal weeks were used to determine, immunocytochemically, putative changes of GABA(A) receptor beta2/3 subunits, GABA(B) receptor (R1a and R1b splice variants), and GABA(C) receptor rho1 subunit expression and distribution in the superficial, visual layers of the superior colliculus. Immunoreactivity for the GABA(A) receptor beta2/3 subunits was found in the superficial grey layer from birth. The labelling changed with age, with an overall continuous reduction in the number of cells labelled and a significant increase in the labelling intensity distribution (neuropil vs soma). Further analysis revealed an initial increase in the labelling intensity between postnatal days 0 and 7 in parallel with an overall reduction of labelled neurones. This was followed by a significant decrease in labelling intensity distribution between postnatal days 7 and 16, and a subsequent increase in intensity between postnatal days 16 and 28. The labelling profiles for GABA(B) receptors (R1a and R1b splice variants) and GABA(C) receptors (rho1 subunit) showed similar patterns. Both receptors could be found in the superficial layers of the superior colliculus from birth, and the intensity and distribution of labelling remained constant during the first postnatal month. However, the cell body count showed a significant decrease between postnatal days 7 and 16. These changes may be related to the time-point of eye opening, which occurred approximately two weeks after birth. For all three receptor types, the cell body count remained constant after postnatal day 16. By four weeks of age, there was no significant difference between the cell numbers obtained for the different receptors. Both GABA itself and neurofilament labelling were also obtained in the superficial superior colliculus at birth. Neurofilament, although found at birth, showed very little ordered arrangement until 16days after birth. When slices were double labelled for GABA(C) receptors and neurofilament, some overlap was observed. Double labelling for the presynaptic protein synaptophysin and GABA(C) receptors showed proximity in some places, indicative of a partly synaptic location of GABA(C) receptors. When GABA(C) and GABA(A) receptors were labelled simultaneously, some but not all neurones showed immunoreactivity for both receptor types. In conclusion, all three GABA receptor types were found to be present in the superior colliculus from birth, and all show some form of postnatal modification, with GABA(A) receptors demonstrating the most dramatic changes. However, GABA(B) and GABA(C) receptors are modified significantly around the onset of input-specific activity. Together, this points towards a contribution of the GABAergic system to processes of postnatal maturation in the superficial superior colliculus.

List-strength effect: I. Data and discussion.

Extra items added to a list cause memory for the other items to decrease (the list-length effect). In one of the present studies we show that strengthening (or weakening) some items on a list harms (helps) free recall of the remaining list items. This is termed the list-strength effect. However, in seven recognition studies the list-strength effect was either absent or negative. This held whether strengthening was accomplished by extra study time or extra repetitions. The seven studies used various means to control rehearsal strategies, thereby providing evidence against the possibility that the findings were due to redistribution of rehearsal or effort from stronger to weaker items within a list. Current models appear unable to predict these results. We suggest that different retrieval operations underlie recall and recognition, as in the SAM model of Gillund and Shiffrin (1984), which can be made to fit the results with certain relatively minor modifications.

List-strength effect: II. Theoretical mechanisms.

Ratcliff, Clark, and Shiffrin (1990) examined the list-strength effect: the effect of strengthening (or weakening) some list items upon memory for other list items. The list-strength effect was missing or negative in recognition, missing or positive in cued recall, and large and positive in free recall. We show that a large number of current models fail to predict these findings. A variant of the SAM model of Gillund and Shiffrin (1984), involving a differentiation hypothesis, can handle the data. A variant of MINERVA 2 (Hintzman, 1986, 1988) comes close but has some problems. Successful variants of a variety of composite and network models were not found (e.g., Ackley, Hinton, & Sejnowski, 1985; Anderson, 1972, 1973; Metcalfe Eich, 1982; Murdock, 1982; Pike, 1984). The results suggest constraints on the future development of such models.

Group collaboration in recognition memory.

Group collaboration was examined in item and associative recognition. The present study distinguishes between group effects versus collaborative processes and defines the latter as interactive information exchange among group members. By that definition, many group effects do not involve collaboration. For example, group performance can exceed individual performance by pooling the increased resources of the group. Specifically, a group advantage can be obtained by deferring to a majority vote or to the group's best member. For both item and associative recognition, a group advantage was obtained that could not be accounted for by resource pooling. Collaborative facilitation was shown reliably in recognizing targets but not for rejecting distractors.

Rules and exemplars in categorization, identification, and recognition.

Subjects learned to classify perceptual stimuli varying along continuous, separable dimensions into rule-described categories. The categories were designed to contrast the predictions of a selective-attention exemplar model and a simple rule-based model formalizing an economy-of-description view. Converging evidence about categorization strategies was obtained by also collecting identification and recognition data and by manipulating strategies via instructions. In free-strategy conditions, the exemplar model generally provided an accurate quantitative account of identification, categorization, and recognition performance, and it allowed for the interrelationship of these paradigms within a unified framework. Analyses of individual subject data also provided some evidence for the use of rules, but in general, the rules seemed to have a great deal in common with exemplar storage processes. Classification and recognition performance for subjects given explicit instructions to use specific rules contrasted dramatically with performance in the free-strategy conditions and could not be predicted by the exemplar model.

Global matching models of recognition memory: How the models match the data.

We present a review of global matching models of recognition memory, describing their theoretical origins and fundamental assumptions, focusing on two defining properties: (1) recognition is based solely on familiarity due to a match of test items to memory at a global level, and (2) multiple cues are combined interactively. We evaluate the models against relevant data bearing on issues including the representation of associative information, differences in verbal and environmental context effects, list-length, list-strength, and global similarity effects, and ROC functions. Two main modifications to the models are discussed: one based on the representation of associative information, and the other based on the addition of recall-like retrieval mechanisms.

Does the Conners' Continuous Performance Test aid in ADHD diagnosis?

The performance of clinic-referred children aged 6-11 (N = 100) was examined using the Conners' Continuous Performance Test (CPT) and measures of auditory attention (Auditory Continuous Performance Test; ACPT), phonological awareness, visual processing speed, and visual-motor competence. The Conners' CPT overall index was unrelated to measures of visual processing speed or visual-motor competence. Although the Conners' CPT converged with the ACPT, the latter demonstrated age and order effects. Significant variance in Conners' CPT parameters was predicted by phonological awareness measures, suggesting that Reading Disordered (RD) children could be "false positives" on the Conners' CPT. The Conners' CPT overall index, phonological awareness, and visual-motor measures were submitted to a 2 x 2 MANCOVA (ADHD vs. RD, covarying for age and socioeconomic status): a main effect for RD status was found. Children with ADHD did not have higher Conners' CPT scores than did clinical controls; however, children with Reading Disorders did. Phonological measures distinguished RD children from ADHD children and other clinical controls. ADHD children who failed the Conners' CPT were rated by teachers as more hyperactive. Despite the strengths of the Conners' CPT, its utility for differential diagnosis of ADHD is questioned.

Does victimization account for sex differences in depressive symptoms?

Women are more depressed than men, and more frequently victimized. We explored the possibility that childhood sexual abuse (CSA) and adult victimization account for the higher levels of depression in women. Depressive symptoms and victimization histories were compared in a sample of 91 men and 76 women seeking out-patient psychotherapy. The women were more depressed, and more likely to have a history of CSA than the men. CSA accounted for a significant proportion of the sex difference in depression levels. The women also were more likely to have been victimized as adults than were the men. However, adult victimization was not associated with higher depression levels, and, therefore, did not account further for the sex difference.

Scintigraphic evaluation of glomus tumours.

The current investigations of choice for a suspected glomus tumour are either direct or indirect angiography to include digital subtraction followed by computerized tomography (CT) or magnetic resonance imaging (MRI) or, if available, CT and MRI with gadolinium alone. Although these modalities confirm the diagnosis and give anatomical information to facilitate accurate staging, they do not provide functional data. The use of radionuclide scintigraphy can add an extra physiological dimension to glomus tumour imaging. Iodine-131/123 metaiodobenzylguanidine (MIBG) is a tumour imaging agent which has been used to diagnose head and neck neuroendocrine tumours to include paragangliomata and medullary carcinoma of the thyroid (MCT). However, it is expensive and the new head and neck tumour imaging agent technetium-99 m (Tc99m) (v) dimercaptosuccinic acid (DMSA) has superceded it as the imaging agent of choice to evaluate MCT. We report a patient with a glomus jugulare tumour which was evaluated with I131/I123-MIBG and Tc99m (v) DMSA. The tumour was functional and is the first reported case exhibiting positive accumulation of both I131-MIBG and Tc99m (v) DMSA. The patient was subsequently treated with a therapeutic dose of I131-MIBG. The significance of these results is discussed.

Grief reactions and recovery in a support group for people bereaved by suicide.

Recent controlled studies have demonstrated that there are few quantitative, but a number of qualitative differences between those bereaved by suicide and those bereaved in other ways. Observations from participants in a support group of those bereaved through suicide are presented here. Guidelines are offered concerning therapy for those who are so clearly distressed by this mode of death.

A support group for people bereaved through suicide.

Although much research has been performed in recent years on the prevention of suicide, less attention has been focused on helping the persons left behind. This article outlines the history of establishing a support group for people who have been bereaved through suicide in an Australian city. It describes the difficulties in establishing the group, its structure, management, and helping functions, and the experiences gained from the initial 7 years of operation. The article has been written in response to requests from medical, social, and lay agencies for information in establishing similar support groups.

Relation between sports context, competitive trait anxiety, perceived ability, and self-presentation confidence.

This study examined the relations among athletic context, i.e., team-sport versus individual-sport, competitive trait anxiety, perceived ability, and self-presentation confidence for 62 men and 34 women athletes. The analyses showed that the athletic context is associated with variations in competitive trait anxiety and self-presentation confidence; however, no main effect or interaction was noted for perceived ability. Results support the notion that aspects of the sports context are significantly related to various precompetitive cognitions.