Geometric control of myogenic cell fate.

This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle cell fate in a geometric pattern. Embedded GF and DF signal progenitor cells from specifically defined areas on the ECM successfully competed against culture media for myogenic cell fate determination at a clearly defined boundary. Differentiation of myoblasts into myotubes is induced in growth-promoting medium, myotube formation is delayed in differentiation-promoting medium, and myogenic cells, at different stages of proliferation and differentiation, can be induced to coexist adjacently in identical culture media. This method can be used to identify molecular interactions between cells in different stages of myogenic differentiation, which are likely to be important determinants of tissue repair. The designed ECM niches can be further developed into a vehicle for transplantation of myogenic progenitor cells maintaining their regenerative potential. Additionally, this work may also serve as a general model to engineer synthetic cellular niches to harness the regenerative potential of organ stem cells

Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome

Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of non-specific abdominal pain. No underlying cause was evident despite extensive diagnostic work-up. More recently she was diagnosed with gall bladder stones. Abdominal ultrasound, computerised tomography and magnetic resonance imaging revealed no pathologic findings apart from cholelithiasis. Endoscopic ultrasound revealed a 5.5 mm pancreatic lesion. Fine needle aspiration showed cells focally expressing chromogranin, suggestive but not diagnostic of a low grade neuroendocrine tumor. OctreoScan(®) was negative. Serum glucagon was elevated to 66 pmol/L (normal: 0-50 pmol/L). Other gut hormones, chromogranin A and chromogranin B were normal. Cholecystectomy and enucleation of the pancreatic lesion were undertaken. Postoperatively, abdominal symptoms resolved and serum glucagon dropped to 7 pmol/L. Although H and E staining confirmed normal pancreatic tissue, immunohistochemistry was initially thought to be suggestive of alpha cell hyperplasia. A count of glucagon positive cells from 5 islets, compared to 5 islets from 5 normal pancreata indicated that islet size and glucagon cell ratios were increased, however still within the wide range of normal physiological findings. Glucagon receptor gene (GCGR) sequencing revealed a heterozygous deletion, K349_G359del and 4 missense mutations. This case may potentially represent a progenitor stage of glucagon cell adenomatosis with hyperglucagonemia in the absence of glucagonoma syndrome. The identification of novel GCGR mutations suggests that these may represent the underlying cause of this condition

Lessons from Love-Locks: The archaeology of a contemporary assemblage

This document is the Accepted Manuscript version. The final, definitive version of this paper has been published in Journal of Material Culture, November 2017, published by SAGE Publishing, All rights reserved.Loss of context is a challenge, if not the bane, of the ritual archaeologist’s craft. Those who research ritual frequently encounter difficulties in the interpretation of its often tantalisingly incomplete material record. Careful analysis of material remains may afford us glimpses into past ritual activity, but our often vast chronological separation from the ritual practitioners themselves prevent us from seeing the whole picture. The archaeologist engaging with structured deposits, for instance, is often forced to study ritual assemblages post-accumulation. Many nuances of its formation, therefore, may be lost in interpretation. This paper considers what insights an archaeologist could gain into the place, people, pace, and purpose of deposition by recording an accumulation of structured deposits during its formation, rather than after. To answer this, the paper will focus on a contemporary depositional practice: the love-lock. This custom involves the inscribing of names/initials onto a padlock, its attachment to a bridge or other public structure, and the deposition of the corresponding key into the water below; a ritual often enacted by a couple as a statement of their romantic commitment. Drawing on empirical data from a three-year diachronic site-specific investigation into a love-lock bridge in Manchester, UK, the author demonstrates the value of contemporary archaeology in engaging with the often enigmatic material culture of ritual accumulations.Peer reviewe

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

Prevalence of Oral Pain and Barriers to use of Emergency Oral Care Facilities Among Adult Tanzanians.

Oral pain has been the major cause of the attendances in the dental clinics in Tanzania. Some patients postpone seeing the dentist for as long as two to five days. This study determines the prevalence of oral pain and barriers to use of emergency oral care in Tanzania. Questionnaire data were collected from 1,759 adult respondents aged 18 years and above. The study area covered six urban and eight rural study clusters, which had been selected using the WHO Pathfinder methodology. Chi-square tests and logistic regression analyses were performed to identify associations.\ud Forty two percent of the respondents had utilized the oral health care facilities sometimes in their lifetime. About 59% of the respondents revealed that they had suffered from oral pain and/or discomfort within the twelve months that preceded the study, but only 26.5% of these had sought treatment from oral health care facilities. The reasons for not seeking emergency care were: lack of money to pay for treatment (27.9%); self medication (17.6%); respondents thinking that pain would disappear with time (15.7%); and lack of money to pay for transport to the dental clinic (15.0%). Older adults were more likely to report that they had experienced oral pain during the last 12 months than the younger adults (OR = 1.57, CI 1.07-1.57, P < 0.001). Respondents from rural areas were more likely report dental clinics far from home (OR = 5.31, CI = 2.09-13.54, P < 0.001); self medication at home (OR = 3.65, CI = 2.25-5.94, P < 0.001); and being treated by traditional healer (OR = 5.31, CI = 2.25-12.49, P < 0.001) as reasons for not seeking emergency care from the oral health care facilities than their counterparts from urban areas. Oral pain and discomfort were prevalent among adult Tanzanians. Only a quarter of those who experienced oral pain or discomfort sought emergency oral care from oral health care facilities. Self medication was used as an alternative to using oral care facilities mainly by rural residents. Establishing oral care facilities in rural areas is recommended

Topological surface states above the Fermi level in Hf2Te2 P

We report a detailed experimental study of the band structure of the recently discovered topological material Hf2Te2P. Using the combination of scanning tunneling spectroscopy and angle-resolved photoemission spectroscopy with surface K doping, we probe the band structure of Hf2Te2P with energy and momentum resolution above the Fermi level. Our experiments show the presence of multiple surface states with a linear Dirac-like dispersion, consistent with the predictions from previously reported band-structure calculations. In particular, scanning tunneling spectroscopy measurements provide experimental evidence for the strong topological surface state predicted at 460meV, which stems from the band inversion between Hf-d and Te-p orbitals. This band inversion comprised of more localized d states could result in a better surface-to-bulk conductance ratio relative to more traditional topological insulators

Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer

Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

K2: A new method for the detection of galaxy clusters based on CFHTLS multicolor images

We have developed a new method, K2, optimized for the detection of galaxy clusters in multicolor images. Based on the Red Sequence approach, K2 detects clusters using simultaneous enhancements in both colors and position. The detection significance is robustly determined through extensive Monte-Carlo simulations and through comparison with available cluster catalogs based on two different optical methods, and also on X-ray data. K2 also provides quantitative estimates of the candidate clusters' richness and photometric redshifts. Initially K2 was applied to 161 sq deg of two color gri images of the CFHTLS-Wide data. Our simulations show that the false detection rate, at our selected threshold, is only ~1%, and that the cluster catalogs are ~80% complete up to a redshift of 0.6 for Fornax-like and richer clusters and to z ~0.3 for poorer clusters. Based on Terapix T05 release gri photometric catalogs, 35 clusters/sq deg are detected, with 1-2 Fornax-like or richer clusters every two square degrees. Catalogs containing data for 6144 galaxy clusters have been prepared, of which 239 are rich clusters. These clusters, especially the latter, are being searched for gravitational lenses -- one of our chief motivations for cluster detection in CFHTLS. The K2 method can be easily extended to use additional color information and thus improve overall cluster detection to higher redshifts. The complete set of K2 cluster catalogs, along with the supplementary catalogs for the member galaxies, are available on request from the authors.Comment: Accepted in ApJ. 25 pages, including 10 figures. Latex with emulateapj v03/07/0