Accumulation, localization, and compartmentation of transforming growth factor beta during endochondral bone development.

Endochondral bone formation was induced in postnatal rats by implantation of demineralized rat bone matrix. Corresponding control tissue was generated by implanting inactive extracted bone matrix, which did not induce bone formation. At various times, implants were removed and sequentially extracted with guanidine hydrochloride, and then EDTA and guanidine hydrochloride. Transforming growth factor beta (TGF beta) in the extracts was quantitated by a radioreceptor assay. TGF beta was present in demineralized bone matrix before implantation, and the concentration had decreased by 1 d after implantation. Thereafter, TGF beta was undetectable by radioreceptor assay until day 9. From day 9-21 the TGF beta was extracted only after EDTA demineralization, indicating tight association with the mineralized matrix. During this time, the content of TGF beta per milligram soluble protein rose steadily and remained high through day 21. This increased concentration correlated with the onset of vascularization and calcification of cartilage. TGF beta was detected only between days 3-9 in the controls; i.e., non-bone-forming implants. Immunolocalization of TGF beta in bone-forming implants revealed staining of inflammatory cells at early times, followed later by staining of chondrocytes in calcifying cartilage and staining of osteoblasts. The most intense staining of TGF beta was found in calcified cartilage and mineralized bone matrix, again indicating preferential compartmentalization of TGF beta in the mineral phase. In contrast to the delayed expression of TGF beta protein, northern blot analysis showed TGF beta mRNA in implants throughout the sequence of bone formation. The time-dependent accumulation of TGF beta when cartilage is being replaced by bone in this in vivo model of bone formation suggests that TGF beta may play a role in the regulation of ossification during endochondral bone development

Inhibitory, GABAergic nerve terminals decrease at sites of focal epilepsy.

Using an immunocytochemical method for the localization of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD), we have observed GABAergic nerve terminals distributed throughout all layers of normal monkey sensorimotor cortex. These terminals displayed ultrastructural characteristics that suggested that they arose from aspinous and sparsely spinous stellate neurons. In monkeys (Macaca mulatta and M. fascicularis) made epileptic by cortical application of alumina gel, a highly significant numerical decrease of GAD-positive nerve terminals occurred at sites of seizure foci indicating a functional loss of GABAergic inhibitory synapses. A loss of such inhibition at seizure foci could lead to epileptic activity of cortical pyramidal neurons

Deep learning-based insights on T:R ratio behaviour during prolonged screening for S-ICD eligibility.

Peer reviewedPublisher PD

Role of deep learning methods in screening for subcutaneous implantable cardioverter defibrillator in heart failure.

Peer reviewedPublisher PD

Automatic mental processes, automatic actions and behaviours in game transfer phenomena: an empirical self-report study using online forum data

Previous studies have demonstrated that the playing of videogames can have both intended and unintended effects. The purpose of this study was to investigate the influence of videogames on players’ mental processes and behaviours in day-to-day settings. A total of 1,023 self-reports from 762 gamers collected from online videogame forums were classified, quantified, described and explained. The data include automatic thoughts, sensations and impulses, automatic mental replays of the game in real life, and voluntary/involuntary behaviours with videogame content. Many gamers reported that they had responded – at least sometimes – to real life stimuli as if they were still playing videogames. This included overreactions, avoidances, and involuntary movements of limbs. These experiences lasted relatively short periods of time but in a minority of players were recurrent. The gamers' experiences appeared to be enhanced by virtual embodiment, repetitive manipulation of game controls, and their gaming habits. However, similar phenomena may also occur when doing other non-gaming activities. The implications of these game transfer experiences are discussed

Tumor cell nuclei soften during transendothelial migration

During cancer metastasis, tumor cells undergo significant deformation in order to traverse through endothelial cell junctions in the walls of blood vessels. As cells pass through narrow gaps, smaller than the nuclear diameter, the spatial configuration of chromatin must change along with the distribution of nuclear enzymes. Nuclear stiffness is an important determinant of the ability of cells to undergo transendothelial migration, yet no studies have been conducted to assess whether tumor cell cytoskeletal or nuclear stiffness changes during this critical process in order to facilitate passage. To address this question, we employed two non-contact methods, Brillouin confocal microscopy (BCM) and confocal reflectance quantitative phase microscopy (QPM), to track the changes in mechanical properties of live, transmigrating tumor cells in an in vitro collagen gel platform. Using these two imaging modalities to study transmigrating MDA-MB-231, A549, and A375 cells, we found that both the cells and their nuclei soften upon extravasation and that the nuclear membranes remain soft for at least 24 h. These new data suggest that tumor cells adjust their mechanical properties in order to facilitate extravasation

HIV-Related Knowledge and Practices among Asian and African Migrants Living in Australia: Results from a Cross-Sectional Survey and Qualitative Study

Australian HIV notification rates are higher for people born in Northeast Asia, Southeast Asia and sub-Saharan Africa compared to Australian-born people. The Migrant Blood-Borne Virus and Sexual Health Survey represents the first attempt to build the national evidence base regarding HIV knowledge, risk behaviors and testing among migrants in Australia. To inform survey development, preliminary qualitative research was conducted with a convenience sample of n = 23 migrants. A survey was developed with reference to the qualitative data and existing survey instruments. Non-probability sampling of adults born in Northeast Asia, Southeast Asia and sub-Saharan Africa was undertaken (n = 1489), and descriptive and bivariate analyses of data were conducted. Knowledge of pre-exposure prophylaxis was low (15.59%), and condom use at last sexual encounter was reported by 56.63% of respondents engaging in casual sex, and 51.80% of respondents reported multiple sexual partners. Less than one-third (31.33%) of respondents reported testing for any sexually transmitted infection or blood-borne virus in the previous two years and, of these, less than half (45.95%) tested for HIV. Confusion surrounding HIV testing practices was reported. These findings identify policy interventions and service improvements critically needed to reduce widening disparities regarding HIV in Australia

Classical Conformal Blocks and Accessory Parameters from Isomonodromic Deformations

Classical conformal blocks naturally appear in the large central charge limit of 2D Virasoro conformal blocks. In the $AdS_{3}/CFT_{2}$ correspondence, they are related to classical bulk actions and are used to calculate entanglement entropy and geodesic lengths. In this work, we discuss the identification of classical conformal blocks and the Painlev\'e VI action showing how isomonodromic deformations naturally appear in this context. We recover the accessory parameter expansion of Heun's equation from the isomonodromic $\tau$-function. We also discuss how the $c = 1$ expansion of the $\tau$-function leads to a novel approach to calculate the 4-point classical conformal block.Comment: 32+10 pages, 2 figures; v3: upgraded notation, discussion on moduli space and monodromies, numerical and analytic checks; v2: added refs, fixed emai

North Flinders Reef (Coral Sea, Australia) Porites sp. corals as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Corals are unique in the suite of proposed Anthropocene Global Boundary Stratotype Section and Point (GSSP) archives, as living organisms that produce aragonite exoskeletons preserved in the geological record that contain highly accurate and precise (<±1 year) internal chronologies. The GSSP candidate site North Flinders Reef in the Coral Sea (Australia) is an offshore oceanic reef, and therefore less vulnerable to local human influences than those closer to the coast. Here, we present geochemical records from two Porites sp. corals sampled at an annual to pluri-annual (i.e. 3–5 years) resolution that shows clear global and regional human impacts. Atmospheric nuclear bomb testing by-products (14C,239+240Pu) show a clear increase in the Flinders Reef corals coincident with well-dated nuclear testing operations. By contrast, the radionuclides 241Am and 137Cs are present at low or undetectable levels, as are spheroidal carbonaceous fly-ash particles. Coral δ13C shows centennial variability likely influenced by growth effects in the 18th century and with a progression to lower values starting in 1880 and accelerating post-1970. The latter may be related to the Suess Effect resulting from 13C-depleted fossil fuel burning. Coral δ15N decreased between 1710 and 1954 with a reversal post-1954. Coral temperature proxies indicate prominent centennial variability with equally warm conditions in the 18th and end of 20th century. However, the exact mechanisms responsible for the mid-20th century changes in these parameters need to be scrutinised in further detail. Plain Language summary: This work proposes a candidate natural archive for the official marker of the Anthropocene that geologists will use to mark this important interval in time. Our candidate is a live coral from North Flinders Reef in the Coral Sea (Australia), located 150 km east of the Great Barrier Reef, a location that is remote from direct local human influences. Corals are a unique archive of tropical ocean change because they incorporate the geochemical signature from seawater into their limestone skeleton during their long life-spans. Here we investigated a number of geochemical markers in yearly growth layers of the corals to define several markers for the Anthropocene based on changes in temperature, water chemistry, chemicals from pollution and fertilisers, radioactive products from nuclear bomb testing, and by-products from burning fossil fuels. We have detected clear human influences in several of these markers

Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel