An integrated gene regulatory network controls stem cell proliferation in teeth.

Epithelial stem cells reside in specific niches that regulate their self-renewal and differentiation, and are responsible for the continuous regeneration of tissues such as hair, skin, and gut. Although the regenerative potential of mammalian teeth is limited, mouse incisors grow continuously throughout life and contain stem cells at their proximal ends in the cervical loops. In the labial cervical loop, the epithelial stem cells proliferate and migrate along the labial surface, differentiating into enamel-forming ameloblasts. In contrast, the lingual cervical loop contains fewer proliferating stem cells, and the lingual incisor surface lacks ameloblasts and enamel. Here we have used a combination of mouse mutant analyses, organ culture experiments, and expression studies to identify the key signaling molecules that regulate stem cell proliferation in the rodent incisor stem cell niche, and to elucidate their role in the generation of the intrinsic asymmetry of the incisors. We show that epithelial stem cell proliferation in the cervical loops is controlled by an integrated gene regulatory network consisting of Activin, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Follistatin within the incisor stem cell niche. Mesenchymal FGF3 stimulates epithelial stem cell proliferation, and BMP4 represses Fgf3 expression. In turn, Activin, which is strongly expressed in labial mesenchyme, inhibits the repressive effect of BMP4 and restricts Fgf3 expression to labial dental mesenchyme, resulting in increased stem cell proliferation and a large, labial stem cell niche. Follistatin limits the number of lingual stem cells, further contributing to the characteristic asymmetry of mouse incisors, and on the basis of our findings, we suggest a model in which Follistatin antagonizes the activity of Activin. These results show how the spatially restricted and balanced effects of specific components of a signaling network can regulate stem cell proliferation in the niche and account for asymmetric organogenesis. Subtle variations in this or related regulatory networks may explain the different regenerative capacities of various organs and animal species

Anticancer chemotherapy in teenagers and young adults: managing long term side effects.

SSA is supported by the Cambridge Cancer Centre.This is the final version of the article. It first appeared from BMJ Group at http://dx.doi.org/10.1136/bmj.i4567

Independent adaptation mechanisms for numerosity and size perception provide evidence against a common sense of magnitude

Abstract How numerical quantity is processed is a central issue for cognition. On the one hand the “number sense theory” claims that numerosity is perceived directly, and may represent an early precursor for acquisition of mathematical skills. On the other, the “theory of magnitude” notes that numerosity correlates with many continuous properties such as size and density, and may therefore not exist as an independent feature, but be part of a more general system of magnitude. In this study we examined interactions in sensitivity between numerosity and size perception. In a group of children, we measured psychophysically two sensory parameters: perceptual adaptation and discrimination thresholds for both size and numerosity. Neither discrimination thresholds nor adaptation strength for numerosity and size correlated across participants. This clear lack of correlation (confirmed by Bayesian analyses) suggests that numerosity and size interference effects are unlikely to reflect a shared sensory representation. We suggest these small interference effects may rather result from top-down phenomena occurring at late decisional levels rather than a primary “sense of magnitude”

Ispitivanje kvaliteta podzemnih, izvorskih i rečnih voda sa područja jugoistočne Srbije

The study deals with mineral characterisation of natural waters from South-East Serbia. The contents of aluminium, arsenic, calcium, cadmium, cobalt, chromium, cooper, iron, potassium, magnesium, manganese, sodium, nickel, lead and zinc were analysed in spring, ground and river waters by inductively coupled plasma-atomic emission spectrometry (ICPAES) technique. The study area was in the Southern Serbia, and included slopes of Rtanj, Ozren, Bukovik, Vrdenik and Čemernik mountains, and the valley of South Morava. Obtained contents were compared with Serbian regulations on the quality of water for human use, and directive of World Health Organization (WHO) for maximum allowed concentrations of chemical substances. High contents of macro-elements, namely calcium, magnesium and potassium, were detected in several spring and ground water samples which are believed to be due to direct influence of rock minerals. Some water samples contained iron, manganese and copper in concentration up to 168.3, 8.10 and 14.9 μg dm-3, respectively, but within the permissible limits. Other heavy metals were not detected in analysed samples. Based on the derived results, tested ground and spring water samples have significant potential to be used as sources for the production of bottled water, but further investigations are necessary. Additional investigations have to be focused on complete physical, chemical and microbiological assessments of water resources. Systematic hydrogeological assessment also should be performed in all seasons. In the meantime, precautionary measures should be immediately taken to protect and preserve these water resources.Ovaj rad predstavlja analizu kvaliteta prirodnih voda iz jugoistočne Srbije. Sadržaj arsena, aluminijuma, kalcijuma, kadmijuma, kobalta, hroma, bakra, gvožđa, kalijuma, magnezijuma, mangana, natrijuma, nikla, olova i cinka je određivan u izvorskim i podzemnim vodama, kao i u rečnoj vodi. Analiza navedenih elemenata je izvedena ICP-AES tehnikom. Analizirani su uzorci voda iz oblasti jugoistočne Srbije, uključujući područja planine Rtnja, Ozrena, Bukovika, Vrdenika i Čemernika, kao i područje doline reke Južne Morave. Određeni sadržaji analiziranih elemenata su poređeni sa važećim pravilnicima Republike Srbije i preporukama Svetske zdravstvene organizacije (SZO). Visoki sadržaj makro-elemenata, odnosno kalcijuma, magnezijuma i kalijuma uočeni su u izvorskim i nekoliko uzoraka podzemnih voda, što može biti posledica direktnog uticaja magmatskih stena. Pojedini uzorci voda su sadržali nešto više sadržaje gvožđa, mangana i bakra u koncentraciji do 168,3, 8,10 i 14,9 μg dm-3, redom, ali u granicama propisanim Pravilnikom i u skladu da preporukama SZO. Ostali teški metali nisu detektovani u ispitivanim uzorcima. Na osnovu dobijenih rezultata se može zaključiti da testirani uzorci podzemnih i izvorskih voda imaju značajan potencijal u smislu proizvodnje flaširane vode, uz neophodna dodatna istraživanja. Dodatna istraživanja bi trebalo usmeriti na kompletnu hemijsku analizu i ispitivanje fizičkih i mikrobioloških karakteristika uzoraka voda. Pored toga, neophodno je sprovesti sistematsko hidrogeološko ispitivanje izdašnosti podzemnih i izvorskih voda tokom svih godišnjih doba. U međuvremenu treba preduzeti mere predostrožnosti kako bi se ovi vodeni resursi zaštitili i očuvali

Motor learning outcomes of handrim wheelchair propulsion during active spinal cord injury rehabilitation in comparison with experienced wheelchair users

Purpose: To investigate changes in wheelchair propulsion technique and mechanical efficiency across first five weeks of active inpatient spinal cord injury rehabilitation and to compare the outcomes at discharge with experienced wheelchair users with spinal cord injury. Methods: Eight individuals with recent spinal cord injury performed six weekly submaximal exercise tests. The first and last measurement additionally contained a wheelchair circuit and peak graded exercise test. Fifteen experienced individuals performed all above-mentioned tests on one occasion. Results: Mechanical efficiency and propulsion technique did not change during the five weeks of inpatient rehabilitation. Peak power output during peak graded test and performance time on the wheelchair circuit improved between the first and the last week. No difference in propulsion technique, peak power output, and performance time was found between the persons with a recent injury and the experienced group. Mechanical efficiency was higher after the correction for the difference in relative power output in the experienced group. Conclusion: The group with a recent injury did not improve mechanical efficiency and propulsion technique over the period of active rehabilitation, despite significant improvements on the wheelchair circuit and in work capacity. The only significant difference between the groups was found in mechanical efficiency. Implications for rehabilitation The lack of time-dependent changes in mechanical efficiency and propulsion technique in the group with a recent spinal cord injury, combined with the lack of differences in technique, work capacity and on the wheelchair circuit between the groups, suggest that important adaptations of motor learning may happen even earlier in rehabilitation and emphasize that the group in active rehabilitation was relatively skilled. Standardized observational analyses of handrim wheelchair propulsion abilities during early spinal cord injury rehabilitation provide detailed understanding of wheelchair technique, skill as well as wheelchair propulsion capacity. Measurement of external power output is critical to interpretation of gross efficiency, propulsion technique, and capacity. Wheelchair quality and body weight - next to wheelchair fitness and skill - require careful consideration both in early rehabilitation as well as in the chronic phase of spinal cord injury

Identifying continuous quality improvement publications: what makes an improvement intervention ‘CQI’?

Background: The term continuous quality improvement (CQI) is often used to refer to a method for improving care, but no consensus statement exists on the definition of CQI. Evidence reviews are critical for advancing science, and depend on reliable definitions for article selection. Methods: As a preliminary step towards improving CQI evidence reviews, this study aimed to use expert panel methods to identify key CQI definitional features and develop and test a screening instrument for reliably identifying articles with the key features. We used a previously published method to identify 106 articles meeting the general definition of a quality improvement intervention (QII) from 9427 electronically identified articles from PubMed. Two raters then applied a six-item CQI screen to the 106 articles. Results: Per cent agreement ranged from 55.7% to 75.5% for the six items, and reviewer-adjusted intra-class correlation ranged from 0.43 to 0.62. ‘Feedback of systematically collected data’ was the most common feature (64%), followed by being at least ‘somewhat’ adapted to local conditions (61%), feedback at meetings involving participant leaders (46%), using an iterative development process (40%), being at least ‘somewhat’ data driven (34%), and using a recognised change method (28%). All six features were present in 14.2% of QII articles. Conclusions: We conclude that CQI features can be extracted from QII articles with reasonable reliability, but only a small proportion of QII articles include all features. Further consensus development is needed to support meaningful use of the term CQI for scientific communication

Cytotoxicity of albebetin oligomers depends on cross-β-sheet formation

AbstractPrefibrillar cytotoxicity was suggested as a common amyloid characteristic. We showed two types of albebetin prefibrillar oligomers are formed during incubation at pH 7.3. Initial round-shaped oligomers consist of 10–15 molecules determined by atomic force microscopy, do not bind thioflavin-T and do not affect viability of granular neurons and SH-SY5Y cells. They are converted into ca. 30–40-mers possessing cross-β-sheet and reducing viability of neuronal cells. Neither monomers nor fibrils possess cytotoxicity. We suggest that oligomeric size is important for stabilising cross-β-sheet core critical for cytotoxicity. As albebetin was used as a carrier-protein for drug delivery, examination of amyloidogenicity is required prior polypeptide biomedical applications