Seamount egg-laying grounds of the deep-water skate Bathyraja richardsoni.

Highly localized concentrations of elasmobranch egg capsules of the deep-water skate Bathyraja richardsoni were discovered during the first remotely operated vehicle (ROV) survey of the Hebrides Terrace Seamount in the Rockall Trough, north-east Atlantic Ocean. Conductivity-temperature-depth profiling indicated that the eggs were bathed in a specific environmental niche of well-oxygenated waters between 4·20 and 4·55° C, and salinity 34·95-35·06, on a coarse to fine-grained sandy seabed on the seamount's eastern flank, whereas a second type of egg capsule (possibly belonging to the skate Dipturus sp.) was recorded exclusively amongst the reef-building stony coral Solenosmilia variabilis. The depths of both egg-laying habitats (1489-1580 m) provide a de facto refuge from fisheries mortality for younger life stages of these skates.

Working memory development in children with mild to borderline intellectual disabilities.

BACKGROUND: The purpose of the current cross-sectional study was to examine the developmental progression in working memory (WM) between the ages of 9 and 16 years in a large sample of children with mild to borderline intellectual disabilities (MBID). Baddeley's influential WM model was used as a theoretical framework. Furthermore, the relations between WM on the one hand, and scholastic skills (arithmetic and reading) on the other were examined. METHOD: One hundred and ninety-seven children with MBID between 9 and 16 years old participated in this study. All children completed several tests measuring short-term memory, WM, inhibition, arithmetic and single word reading. RESULTS: WM, visuospatial short-term memory and inhibition continued to develop until around age 15 years. However verbal short-term memory showed no further developmental increases after the age of 10 years. Verbal short-term memory was associated with single word reading, whereas inhibition was associated with arithmetic. DISCUSSION: The finding that verbal short-term memory ceases to develop beyond the age of 10 years in children with MBID contrasts with results of studies involving typically developing children, where verbal short-term memory develops until around age 15 years. This relative early developmental plateau might explain why verbal short-term memory is consistently considered weak in children with MBID.

Assessment of financial impact of foot and mouth disease on smallholder cattle farmers in Southern Cambodia.

The financial impact of an outbreak of FMD in 2010 on 62 smallholder cattle farmers in four villages in southern Cambodia was investigated by a financial impact survey questionnaire. Financial losses associated with FMD infection were severe with variation depending on whether the animal survived or died or was used for draft. The average post-FMD loss varied from USD 216.32, a 54% reduction from the pre-FMD value because of weight loss and treatment costs, to USD 370.54, a 92% reduction from pre-FMD values if the animal was treated, died and a rental draft replacement was required. Partial budget analysis identified a strongly positive incentive for cattle to be vaccinated biannually for FMD, providing USD 31.48 per animal for each animal owned. However low vaccination rates suggest that farmers are mostly unaware of the need or averse to the practice of vaccinating their cattle for FMD. This may be due to poor understanding of preventative disease strategies such as vaccination, unavailable disposable income for purchase of vaccines, and failure to recognize the full costs that are incurred when the disease occurs. Enhancing smallholder cattle productivity through the introduction of forage growing systems has been suggested as a pathway for alleviating rural poverty in the Mekong region. As our financial analysis identified a net benefit of vaccination for smallholder farmer enterprises in an endemic FMD area in Cambodia, it is considered important that farmer education strategies aimed at improving cattle productivity, also include both access to vaccine and training in preventative disease risk management and biosecurity practices in Cambodia.

Endoglin expression in breast tumor cells suppresses invasion and metastasis and correlates with improved clinical outcome.

Tumor growth factor-ß (TGF-ß) signaling in cancer has been implicated in growth suppression of early lesions and enhancing tumor cell invasion and metastasis. However, the cellular mechanisms that determine this signaling output in individual tumors are still largely unknown. In endothelial cells, TGF-ß signaling is modulated by the TGF-ß co-receptor endoglin (CD105). Here we demonstrate that endoglin is expressed in a subset of invasive breast cancers and cell lines and is subject to epigenetic silencing by gene methylation. Endoglin downregulation in non-tumorigenic MCF10A breast cells leads to the formation of abnormal acini in 3D culture, but does not promote cell migration or transformation. In contrast, in the presence of activated ErbB2, endoglin downregulation in MCF10A cells leads to enhanced invasion into a 3D matrix. Consistent with these data, ectopic expression of endoglin in MDA-MB-231 cells blocks TGF-ß-enhanced cell motility and invasion and reduces lung colonization in an in vivo metastasis model. Unlike endothelial cells, endoglin does not modulate Smad-mediated TGF-ß signaling in breast cells but attenuates the cytoskeletal remodeling to impair cell migration and invasion. Importantly, in a large cohort of invasive breast cancers, lack of endoglin expression in the tumor cell compartment correlates with ENG gene methylation and poor clinical outcome.

How does the severity of a learning disability affect working memory performance?

Working memory performance was examined in children aged 11-12 years who had borderline, mild, and moderate learning disabilities. Comparisons with children of average abilities were used to determine whether those with more severe learning disabilities had greater impairments in working memory. Seven measures of working memory span were used to assess temporary phonological short-term storage (digit span, word span), temporary visuo-spatial short-term storage (pattern span, spatial span), and temporary short-term storage with additional processing, or central executive, demands (listening span. odd one out span, reverse digit span). Children with mild and moderate learning disabilities were impaired on all measures of working memory compared to children of average abilities. Children with borderline learning disabilities were just as good as children with average abilities on visuo-spatial and complex span tasks, but showed an impairment on phonological span tasks. Children with moderate learning disabilities were indistinguishable from children with mild learning disabilities on simple span tasks, but were significantly poorer than the mild group on the more demanding complex span tasks. For the group as a whole, working memory was strongly related to mental age.

Participation of transglutaminase in the activation of latent transforming growth factor beta1 in aging articular cartilage.

OBJECTIVE: Transglutaminase (TGase) catalyzes the calcium-dependent crosslinking of polypeptide chains, resulting in posttranslational protein modifications that affect both intracellular and extracellular processes. We previously demonstrated a dramatic elevation of TGase activity levels in aging articular chondrocytes and postulated a role for TGase in the pathologic processes common in aging joints. In several cell systems, TGase participates in the activation of latent transforming growth factor beta (LTGFbeta). Since TGFbeta is a key factor in age-related cartilage diseases, the purpose of the present study was to determine whether TGase from aging articular chondrocytes participates in LTGFbeta activation. METHODS: We measured the ability of old and young porcine articular chondrocytes to activate 10 ng/ml of LTGFbeta1 in the presence and absence of TGase inhibitors. The activity of plasmin, another key participant in LTGFbeta activation, was also measured. RESULTS: Old chondrocytes activated 11+/-1.8% (mean +/- SD) of exogenous LTGFbeta1 at 6 hours, while young chondrocytes activated 4.2+/-0.5% of exogenous LTGFbeta1. The addition of 3 different TGase inhibitors suppressed active TGFbeta1 in the cell layer to levels that were 35-69% of control values in old chondrocytes and had no effect on young chondrocytes. The ability to suppress TGFbeta activation correlated with the ability of each of the TGase inhibitors to inhibit TGase activity. The activity of plasmin, which enzymatically activates LTGFbeta1, did not differ between young and old chondrocytes and was unaffected by TGase inhibition. CONCLUSION: We report here a novel pathologic function for TGase in aging articular cartilage. This work supports a role for elevated TGase activity in age-related arthritis based in part on its participation in the activation of the critical growth factor TGFbeta in articular cartilage.

The development of the use of long-term knowledge to assist short-term recall.

The influence of item familiarity upon memory span was examined in adults and children aged 5, 7, and 10 years by comparing the recall of words and nonwords. Using a probed recall task, both item recall and position recall were tested. The effect of familiarity upon item recall was found to develop with age, from no effects in the 5-year-olds to significant effects in the older children and adults. By contrast, no effect of familiarity was found at any age when recall of position was required. Dissociations between word length effects and familiarity effects supported the conclusion that the familiarity effect does not result from rehearsal. Several explanations for the source of the familiarity effect were examined, and the familiarity effect was attributed to a strategic redintegration or reconstruction process, which is necessary for item recall but not for position recall.

Modality effects and the development of the word length effect in children.

Two experiments investigated the development of the word length effect in children aged 4 to 10 years, comparing auditory and visual stimuli. The question addressed was whether word length effects emerged earlier with auditory presentation or visual presentation, or whether they emerged at the same age regardless of presentation modality. Results provided evidence that word length effects emerge earlier with visual than auditory presentation. The implication of our results is that with visual presentation, 4-year-olds engage in some form of verbalization strategy that involves obtaining phonological representations of picture names and mapping them on to articulatory output plans. This strategy is clearly verbal in nature, but is not necessarily characterised as cumulative verbal rehearsal.

Eyewitness memory and suggestibility in children with mental retardation.

We examined how well children with mental retardation were able to recall a live staged event one day later compared to CA- and MA-comparable peers. Children with mental retardation performed very well on many measures of eyewitness memory performance, reaching the level of the CA-comparable group for free recall, general questions, open-ended questions, and correctly leading questions. They were, however, more suggestible in response to closed misleading questions than were children in the CA-comparable group, although they were not more suggestible than those in the MA-comparable group. Some relationships were found between a standardized measure of suggestibility and performance on the eyewitness memory task, but most of these relationships were not the same within each of our study groups.

Thyroid hormones induce features of the hypertrophic phenotype and stimulate correlates of CPPD crystal formation in articular chondrocytes.

OBJECTIVE: Articular cartilage affected by calcium pyrophosphate dihydrate (CPPD) crystal deposition contains abnormal chondrocytes with morphologic similarities to the terminally differentiated hypertrophic chondrocytes that mineralize in growth plate cartilage. These chondrocytes also elaborate high levels of extracellular inorganic pyrophosphate (PPi), an essential component of the CPPD crystal. Several factors that stimulate articular chondrocyte PPi elaboration also induce terminal differentiation in growth plate chondrocytes. We hypothesized that factors such as thyroid hormones (T3 and T4) that are potent stimulants of growth plate chondrocyte hypertrophy might also stimulate articular chondrocyte hypertrophic differentiation. We also hypothesized that like transforming growth factor-beta (TGF-beta), ascorbate, and retinoic acid, thyroid hormones would increase chondrocyte PPi elaboration. METHODS: We determined the effects of T3, T4, and TGF-beta on markers of the hypertrophic phenotype such as alkaline phosphatase (ALPase) activity and type X collagen production; and the effects of T3 and T4 on processes implicated in CPPD crystal formation including PPi elaboration and nucleoside triphosphate pyrophosphohydrolase (NTPPPH) activity in adult porcine articular chondrocytes in culture. RESULTS: ALPase activity increased 3-fold with T3 and T4 and 1.3-fold with TGF-beta. Type X collagen levels also increased with thyroid hormone treatment. [125I]T3 binding studies proved the existence of saturable T3 receptors on chondrocytes. Media [PPi] and cellular NTPPPH activity significantly increased in cultures treated with 1-10 nM T3 or 100-500 nM T4. CONCLUSION: Increased PPi elaboration is an additional and previously unrecognized feature of hypertrophic differentiation in articular chondrocytes. These terminally differentiated chondrocytes may play a pathogenic role in CPPD crystal deposition disease.

Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles.

OBJECTIVE: Transglutaminases (TGases) (E.C. 2.3.2.13) catalyze a posttranslational modification of proteins and are associated with biomineralization in growth plate cartilage. Type II TGase participates in the activation of latent transforming growth factor beta (TGFbeta), a crucial factor for both normal cartilage mineralization and the pathologic mineralization that results in calcium pyrophosphate dihydrate (CPPD) crystal formation in aging articular cartilage. To explore a possible association between TGase levels and CPPD crystal formation in mature articular cartilage, TGase activity in articular chondrocytes from old and young pigs and in the articular cartilage vesicle (ACV) fraction of porcine articular cartilage was examined. In addition, the effects of TGase inhibitors on the production of inorganic pyrophosphate (PPi), a process necessary for CPPD crystallogenesis, were determined. METHODS: TGase activity was measured with a radiometric assay in cultured articular chondrocytes from the knee joints of old (3-5 years old) and young (2-6 weeks old) pigs and in the ACVs. PPi levels were measured in chondrocyte-conditioned media in the presence of TGase inhibitors or control compounds. RESULTS: Levels of TGase activity in the cytosolic fraction of old chondrocytes were 7-fold higher than those in identically cultured young chondrocytes. The mean +/- SD activity level in the membrane fraction of lysed chondrocytes was 6.0 +/- 0.6 units/mg protein in old articular chondrocytes and was undetectable in young chondrocytes. In ACVs, the mean +/- SD TGase activity level was 1.23 +/- 0.1 units/mg protein. Type II TGase protein was present in chondrocyte cytosol and in ACVs. TGase activity was increased by TGFbeta to 120% of control values (P < 0.01), and decreased by insulin-like growth factor 1 to 80% of control values (P < 0.01). TGase inhibitors blocked media accumulation of PPi, an essential precursor of CPPD crystal formation, and a sensitive marker of TGFbeta effect. CONCLUSION: These data suggest a potential link between TGase activity and processes of pathologic biomineralization that result in CPPD crystal formation in aging articular cartilage.

Retinoic acid stimulates pyrophosphate elaboration by cartilage and chondrocytes.

Abnormal metabolism of extracellular inorganic pyrophosphate (PPi) by articular cartilage contributes to calcium pyrophosphate dihydrate (CPPD) crystal formation and the resultant arthritis known as CPPD deposition disease. The factors causing excess PPi elaboration in affected cartilage remain poorly defined. Retinoic acid (RA), a naturally occurring vitamin A metabolite, promotes cartilage degeneration and mineralization, two correlates of CPPD crystal deposition. RA was examined as a potential modifier of cartilage PPi elaboration. All-trans RA (200-1000 nM) increased PPi levels in culture medium of normal porcine cartilage and chondrocytes 2-3-fold over control values at 96 hours of incubation (P < 0.01). IGF1 and anti-EGF antibody diminished the effects of RA on PPi elaboration. RA modestly increased activity of the PPi-generating ectoenzyme NTPPPH in culture medium (P < 0.01). As some RA effects are mediated through increased activity of TGFbeta, a known PPi stimulant, we examined the effect of anti-TGFbeta antibody on RA-induced PPi elaboration. PPi levels in medium were reduced from 30 +/- 7 microM in cartilage cultures with 500 nM RA to 14 +/- 4 microM PPi in cartilage cultures with RA and anti-TGFbeta. Anti-TGFbeta antibody, however, had no significant effect on RA-induced PPi elaboration in chondrocyte cultures. Thus, RA, along with TGFbeta and ascorbate, can now be included in the list of known PPi stimulants. All three of these factors promote mineralization in growth plate cartilage. These data support a central role for TGFbeta in CPPD disease, and provide further evidence linking processes of normal and pathologic calcification in cartilage.