bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique hues
Authors: Wuerger Sophie , Parkes Laura
Published: August 2014

What computation does the human brain perform when we experience ‘red’, ‘green’, ‘yellow’, or ‘blue’? Where in the visual pathway does the human visual system combine the retinal cone signals (L, M, S) to yield these fundamental colour sensations? Behavioural data show that the four unique hues (red, green, yellow, blue) do not map onto the cone-opponent mechanisms (i.e. L–M; S-(L+M)) found in the Lateral Geniculate Nucleus, a subcortical structure involved in early visual processing. The brain imaging experiment supports the behavioural result: using pattern classification algorithms applied to fMRI brain activation patterns we show that unique hues cannot be classified in the LGN, but we achieve above chance classification in primary visual cortex (V1). Our imaging data provide strong evidence that the unique hues do not originate in subcortical areas, but in the visual cortex, possibly as early as primary visual cortex.
Chapter 4. Middle Stone Age engravings and their significance to the debate on the emergence of symbolic material culture
Authors: Henshilwood Christopher S. , d'Errico Francesco
Published: August 2014

Archaeological evidence associated with modern cognitive abilities provides important insights into when and where modern human behaviour emerged. Modern human behaviour here means the thoughts and actions spontaneously shaped by minds equivalent to those of Homo sapiens today. Key among these is the use of symbols. Three models for the origins of behavioural modernity are current: (i) a late and rapid appearance at ~ 40–50 ka associated with the European Upper Palaeolithic and the Later Stone Age (LSA) of sub-Saharan Africa, (ii) an earlier and more gradual evolution rooted in the African Middle Stone Age (MSA ~ 300–40 ka), (iii) a discontinuous evolution rooted in both the African Middle Stone Age and the Mousterian of Eurasia. Material evidence for modern behaviour before 40 ka in Africa was, until a few years ago, relatively rare and often regarded as ambiguous compared to evidence from the Upper Palaeolithic or LSA. However, in sub-Saharan Africa archaeological evidence for changes in technology, economy and social organization and the emergence of symbolism in the Middle Stone Age contradicts the first model. Examples of these changes include standardized formal lithic tools, shaped bone implements, innovative subsistence strategies, evidence for personal ornaments and the deliberate engraving of abstract designs on ochre, ostrich eggshell and bone. In this chapter we review the earliest evidence for purposely made engravings from southern Africa and discuss their significance for arguments favouring early advances in human cognition.
Chapter 6. The emergence of language, art and symbolic thinking
Authors: Zilhão João
Published: August 2014

There is a widespread understanding that the personal ornaments of the African Middle Stone Age and the animal and human figurines of the Aurignacian of southern Germany provide the earliest evidence of the possession of “modern” cognitive capabilities, ones that appeared for the first time in human evolution as a result of the speciation of Homo sapiens and that would explain its rapid expansion from Africa into Eurasia and the attendant extinction of coeval archaic humans (such as the Neandertals). The archaeological facts contradict this view, since there is abundant evidence for the existence of such “modern” capabilities in non-sapiens populations, and that language, “symbolic thinking” by definition, is probably as old as the human genus. Therefore, the explanation for the emergence of body ornamentation and figurative art must be sought not in the realm of cognition but in that of history, with demographic growth and the intensification of social interaction networks playing a primary role in the process.
Chapter 8. The living as symbols, the dead as symbols
Authors: Pettitt Paul
Published: August 2014

The ‘symbolic capacity’ has come to be seen as a core trait of anatomically modern humans, and probably separates them cognitively and behaviourally from all other hominins. While archaeologists agree on what aspects of the archaeological record constitute evidence of symbolism, such as burials, use of pigments, and personal ornamentation, only generic concepts of ‘symbolism’ are invoked from these, resulting in a simplistic discourse about its origins. I try to problematise the concept of symbolism, using these archaeological categories, breaking each down into differing levels of symbolic sophistication. Following this, I try to link these to Dunbar’s levels of intention, and explore how one might identify these from the archaeological record. I conclude by making a necessarily coarse comparison of Neandertals and modern humans in terms of the expression of these characteristics.
Pragmatics, linguistic competence, and Conversation Analysis
Authors: Antaki Charles
Published: August 2014

Competent speakers have effortless mastery over talk; traditional theories about what happens when that goes wrong tend to locate the problem in the speaker. Conversation Analysis offers a radical alternative, stressing the role of the speaker’s interlocutors and the structures of conversation that all parties can use.
Pragmatics and dialogue phenomena
Authors: Wilks Yorick
Published: August 2014

I argue that the definition of ‘pragmatics’ has drifted a great deal since ­Morris, but that there is much to be said for retaining and emphasizing his original sense of relatedness to an utterer. I discuss the role of a computational modelling of dialogue within that core conception of pragmatics, arguing it should be near the center on that classic definition, although computational models have never been central to linguistic pragmatics. I review the relevance to this strand of pragmatics of the data versus rules debate within computational linguistics over the last twenty years and argue that we must stay with some form of the data-driven approach since the alternative has not been proved productive.
Chapter 12. English influence on Polish proverbial language
Authors: Rozumko Agata
Published: August 2014

The aim of this article is to discuss recent borrowings of English proverbs into Polish. Foreign proverbs are often cited when members of a linguistic community wish to signal their identification with another community, which is why changes in proverbial language may be indicative of the adoption of new cultural patterns by a society. It seems that a few English proverbs have begun to replace outdated Polish sayings, while some others, such as those reflecting patterns of Anglo-American culture, are being added to the stock of traditional Polish proverbs. The present study is corpus based. It discusses the contexts in which the proverbs appear in Polish, the metalinguistic tags used to introduce them, and the cultural significance of these borrowings.
Chapter 13. English direct loans in European football lexis
Authors: Bergh Gunnar , Ohlander Sölve
Published: August 2014

Football language is arguably the world’s most widespread special language, where English has played – and still plays – a dominant role. The present study reports on the influence of English in terms of direct loans in this field, as manifested in 16 European languages. Based on a set of 25 English football words – dribble, goal, offside, hooligan, etc. – the investigation shows that while direct borrowing is common, there is a great deal of variation between the languages studied, Norwegian exhibiting the highest number of foreign loans and Finnish the lowest. The significance of the resulting patterns is discussed, providing some tentative explanations of the phenomena noted, where linguistic, sociolinguistic and cultural factors are taken into account.
Chapter 15. Anglicisms in the discourse of Alitalia’s bailout in the Italian press
Authors: Fusari Sabrina
Published: August 2014

We describe a corpus study of the Anglicisms and false Anglicisms used by two major Italian newspapers (La Repubblica and Corriere della Sera) in their representation of the bailout and privatization of the Italian airline Alitalia. Our aim is to establish if and to what extent the use of new non-adapted Anglicisms in news reports of Alitalia’s crisis and privatization, especially in the domains of economics and aviation, had an impact on the transparency of the information provided. The results show that, in the coverage of this news story, new Anglicisms are often left undefined, or provided with an inappropriate Italian equivalent. This may have made it more difficult for readers to develop a thorough understanding of Alitalia’s crisis and privatization.
Arab Ethnonyms (‘Ajam, ‘Arab, Badū and Turk): The Kurdish Case as a Paradigm for Thinking about Differences in the Middle Ages
Authors: James Boris
Published: August 2014

In general terms, the history of the Kurds in the medieval period—or at least those described as being Kurdish in our sources—has attracted relatively little attention within western academia. Moreover, those scholars who have thought to comment on the subject have in general relied on the work of the eminent Russian orientalist Vladimir Minorsky. Hence there has been very little re-examination of the Arabic sources which Minorsky consulted. This article constitutes a first attempt to re-examine some of the “historical orthodoxy” regarding the meaning and nature of the term Kurd in the Middle Ages. More precisely, it aims at questionning the work of those scholars who argue that, due to its ambiguous usage, the term Kurd in the medieval period did not denote an ethnic people. This paper argues that in fact the very ambiguity surrounding the term is indicative of its ethnonymic value and through an examination of the meaning of the term Kurd in this era we can gain a greater understanding of conceptions of ethnic difference in Arabo-Muslim sources.
RHEX, a novel regulator of human erythroid progenitor cell expansion and erythroblast development
Authors: Verma Rakesh , Su Su , McCrann Donald J. , Green Jennifer M. , Leu Karen , Young Peter R. , Schatz Peter J. , Silva Jeffrey C. , Stokes Matthew P. , Wojchowski Don M.
Published: August 2014

Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 (GRB2)–associated binding proteins 1–3 (GAB1-3), insulin receptor substrate 2 (IRS2), docking protein 1 (DOK1), Src homology 2 domain containing transforming protein 1 (SHC1), and sprouty homologue 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducing adaptor molecule 2 (STAM2) as novel candidate adaptors together with an ORF factor designated as regulator of human erythroid cell expansion (RHEX). RHEX is well conserved in Homo sapiens and primates but absent from mouse, rat, and lower vertebrate genomes. Among tissues and lineages, RHEX was elevated in EPCs, occurred as a plasma membrane protein, was rapidly PY-phosphorylated >20-fold upon EPO exposure, and coimmunoprecipitated with the EPOR. In UT7epo cells, knockdown of RHEX inhibited EPO-dependent growth. This was associated with extracellular signal-regulated kinase 1,2 (ERK1,2) modulation, and RHEX coupling to GRB2. In primary human EPCs, shRNA knockdown studies confirmed RHEX regulation of erythroid progenitor expansion and further revealed roles in promoting the formation of hemoglobinizing erythroblasts. RHEX therefore comprises a new EPO/EPOR target and regulator of human erythroid cell expansion that additionally acts to support late-stage erythroblast development.
Irreducibility of Newton strata in 𝐺𝑈(1,𝑛-1) Shimura varieties
Authors: Achter Jeffrey
Published: August 2014

Let

L
L

be a quadratic imaginary field, inert at the rational prime

p
p

. Fix an integer

n
≥
3

n\ge 3

, and let

M

\mathcal M

be the moduli space (in characteristic

p
p

) of principally polarized abelian varieties of dimension

n
n

equipped with an action by

O

L

\mathcal {O}_L

of signature

(
1
,
n
−
1
)

(1,n-1)

. We show that each Newton stratum of

M

\mathcal M

, other than the supersingular stratum, is irreducible.
APPEX: analysis platform for the identification of prognostic gene expression signatures in cancer
Authors: Kim Seon-Kyu , Hwan Kim Jong , Yun Seok-Joong , Kim Wun-Jae , Kim Seon-Young
Published: August 2014

Summary: Because cancer has heterogeneous clinical behaviors due to the progressive accumulation of multiple genetic and epigenetic alterations, the identification of robust molecular signatures for predicting cancer outcome is profoundly important. Here, we introduce the APPEX Web-based analysis platform as a versatile tool for identifying prognostic molecular signatures that predict cancer diversity. We incorporated most of statistical methods for survival analysis and implemented seven survival analysis workflows, including CoxSingle , CoxMulti , IntransSingle , IntransMulti , SuperPC , TimeRoc and multivariate . A total of 236 publicly available datasets were collected, processed and stored to support easy independent validation of prognostic signatures. Two case studies including disease recurrence and bladder cancer progression were described using different combinations of the seven workflows.

Availability and implementation: APPEX is freely available at http://www.appex.kr .

Contact:  kimsy@kribb.re.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
HLX-1 may be an SS433 system
Authors: King Andrew , Lasota Jean-Pierre
Published: August 2014

We show that the hyperluminous source HLX-1 may be a stellar-mass binary system like SS433, but seen along its X-ray beams. The precession of these beams gives the ∼1 yr characteristic time-scale of the light curve, while the significant X-ray duty cycle means that the precession angle must be comparable with the beam opening angle, which is of the order of 1 $_{.}^{\circ}$6. The X-ray light curve appears to result from geometric collimation and scattering as the beam moves through the line of sight. Encouragingly, the distance ∼95 Mpc suggested for HLX-1 is only a few times larger than the minimum distance at which we can expect to view such a highly beamed system along its axis. This picture allows a simple interpretation of HLX-1 as the most extreme known member of the ultraluminous X-ray source population.
The Fermi bubbles as starburst wind termination shocks
Authors: Lacki Brian C.
Published: August 2014

The enhanced star formation in the inner 100 pc of the Galaxy launches a superwind at ∼1600 km s-1 for M82-like parameters. The ram pressure of the wind is very low compared to more powerful starburst winds. I show that halo gas stops the wind a few kpc from the Galactic Centre. I suggest that the termination shock accelerates cosmic rays, and that the resulting inverse Compton γ-rays are visible as the Fermi bubbles. The bubbles are then wind bubbles, which the starburst can inflate within 10 Myr. They can remain in steady state as long as the starburst lasts. The shock may accelerate PeV electrons and EeV protons. The bubbles may be analogues of galactic wind termination shocks in the intergalactic medium. I discuss the advantages and problems of this model. I note that any jets from Sgr A* must burrow through the starburst wind bubble before reaching the halo gas, which could affect the early evolution of such jets.
Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)
Authors: Bhukya Hussain , Bhujbalrao Ruchika , Bitra Aruna , Anand Ruchi
Published: August 2014

Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class of transcription factors that are induced by γ-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 Å. Binding of the DNA results in the restructuring of the dimeric interface of CprB, inducing a pendulum-like motion of the helix-turn-helix motif that inserts into the major groove. The crystal structure revealed that, CprB is bound to DNA as a dimer of dimers with the mode of binding being analogous to the broad spectrum multidrug transporter protein QacR from the antibiotic resistant strain Staphylococcus aureus. It was demonstrated that the CprB displays a cooperative mode of DNA binding, following a clamp and click model. Experiments performed on a subset of DNA sequences from Streptomyces coelicolor A3(2) suggest that CprB is most likely a pleiotropic regulator. Apart from serving as an autoregulator, it is potentially a part of a network of proteins that modulates the γ-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2).
The bridge of iconicity: from a world of experience to the experience of language
Authors: Perniss Pamela , Vigliocco Gabriella
Published: August 2014

Iconicity, a resemblance between properties of linguistic form (both in spoken and signed languages) and meaning, has traditionally been considered to be a marginal, irrelevant phenomenon for our understanding of language processing, development and evolution. Rather, the arbitrary and symbolic nature of language has long been taken as a design feature of the human linguistic system. In this paper, we propose an alternative framework in which iconicity in face-to-face communication (spoken and signed) is a powerful vehicle for bridging between language and human sensori-motor experience, and, as such, iconicity provides a key to understanding language evolution, development and processing. In language evolution, iconicity might have played a key role in establishingdisplacement(the ability of language to refer beyond what is immediately present), which is core to what language does; in ontogenesis, iconicity might play a critical role in supportingreferentiality(learning to map linguistic labels to objects, events, etc., in the world), which is core to vocabulary development. Finally, in language processing, iconicity could provide a mechanism to account for how language comes to beembodied(grounded in our sensory and motor systems), which is core to meaningful communication.
Imagining the Economic Nation: The Scottish Case
Authors: TOMLINSON JIM
Published: August 2014

The impending Scottish referendum on independence raises the question: what is a nation? This article addresses this question in terms of ‘economic nationhood’. Tracing the development of the Scottish economy over the last century and a half, it shows how the extraordinarily ‘globalised’ economy of pre‐1913 Scotland slowly evolved into a much more self‐reliant entity. Today, Scotland has a de‐industrialised and substantially de‐globalised economy, with a very large public sector about which key decisions are made in Edinburgh. Scotland has become much more of an economic ‘community of fate’ than ever before in its modern history.
Riding a wave: the Company's role in the South Sea Bubble
Authors: Kleer Richard A.
Published: August 2014

It is widely believed that officials of the South Sea Company deliberately engineered London's stock market bubble of 1720, hoping in the process to line their own pockets. This article considers the available evidence, including some manuscript records of securities trading by Company officials, and finds there is little support for the standard view. An alternative account is proposed. The Company had broader aims to which the bubble was in fact a major obstacle. The directors acted to support the market price of South Sea stock whenever it came under downward pressure.
Morphological and Morphometric Description of Female Reproductive Tract of Sapajus apella (Capuchin monkey)
Authors: Lima A. R. , Guimarães S. B. , Branco É. , Giese E. G. , Muniz J. A. P. C. , Pereira W. L. A. , da Cunha P. K. F. , Ricci R. E. , Miglino M. A.
Published: August 2014

Forest destruction has progressively hampered the survival of many species, and this is why it is so important to study of the lives of primates in captivity. This study aimed to describe the morphological aspects of the female reproductive tract of Sapajus apella. We used five animals obtained from the National Primate Center, Ananindeua – PA. The ovaries were paired, compact and symmetrical and had a smooth surface. The uterine tubes were bilateral and convoluted in adult animals and straight in young individuals. The uterus was simple and located in the pelvic region. The vagina was a long structure due to the position of the uterus. The external genitalia were located in the urogenital perineum and consisted of dark pigmented labia majora and labia minora, a vaginal vestibule as long as the vagina and a well‐developed clitoris. The results showed that the genitals of S. apella resemble those of other Neotropical primates.
Outcomes in the surgical treatment of low rectal cancer: does neoadjuvant treatment equalize results?
Authors: Pollett William G. , Gibbs Peter , McLaughlin Stephen , Eteuati Jimmy , Harold Michael , Marion Kaye , Patel Shweta , Jones Ian
Published: August 2014

Background

The choice of operation for potentially curable cancer of the low rectum (≤6 cm from the anal verge) is usually between ultra low anterior resection (ULAR) or abdominal perineal excision (APE). Numerous studies have suggested improved results with ULAR.

Methods

This study was a retrospective review of prospectively collected data for a series of patients undergoing surgical treatment for low rectal cancer at three Melbourne hospitals. The patient details and outcomes were compared between those undergoing APE and ULAR.

Results

One hundred and ninety‐eight of 213 patients with potentially curable low rectal cancer were treated by either ULAR (n = 82) or APE (n = 116). Overall survival and local recurrence rates were similar, although there was a trend towards improved results for ULAR. Preoperative radiation was received by 89 (76.7%) of APE patients and 44 (53.7%) of ULAR patients (P < 0.0005).

Conclusion

In this study there was no statistical difference in the oncological results between APE and ULAR. However, there was a trend to improved result for ULAR in spite of a strikingly higher rate of neoadjuvant radiation in the APE group. It is possible that enhanced use of preoperative radiation has a beneficial role in the management of low rectal cancer treated by conventional APE.
Audit of the association between length of time spent on diagnostic work‐up and tumour stage in patients with symptomatic colon cancer
Authors: Tiong Jimmy , Gray Andrew , Jackson Christopher , Thompson‐Fawcett Mark , Schultz Michael
Published: August 2014

Background

Colorectal cancer is one of the most incident cancers in New Zealand. Due to resource limitations, some patients experienced protracted wait times before reaching a definitive diagnosis. We analysed the relationship between time to diagnosis and clinical stage and reviewed the length of time for components of the diagnostic work‐up to identify priority areas for service improvement. We benchmarked our timeliness against introduced standards.

Methods

This retrospective study included all patients with colonic (not rectal) cancer between October 2007 and September 2009. Patients were stratified into an early and advanced group. Types of delay were calculated from the onset of symptoms to the administration of treatment. The compliance with target waiting times was assessed.

Results

Fifty‐eight patients were included in the early group and 83 patients in the advanced group. There were no significant differences in demographics or symptoms. The work‐up was longer than international benchmarks, but with wide variations. There was no statistical difference between lengths of work‐up in the groups. The advanced group had increased utilization of private and emergency investigations. Forty‐four per cent met the diagnostic colonoscopy target waiting time of 42 days with a trend in favour of the advanced group and 21% received treatment within 62 days (non‐significant).

Conclusion

Current systems are not sophisticated enough to predict the stage of colon cancer. Here, long waiting times were not associated with cancer stage in symptomatic patients. Resources need to be directed to diagnostic colonic imaging.
The STRONGkids nutritional risk screening tool can be used by paediatric nurses to identify hospitalised children at risk
Authors: Moeeni Vesal , Walls Tony , Day Andrew S.
Published: August 2014

Aim

Hospitalised children have higher rates of undernutrition. Early detection of at‐risk patients could lead to prompt preventative or corrective interventions. Several nutritional risk screening tools are available for screening hospitalised children including the STRONGkids tool. This study was designed to assess the usefulness of STRONGkids when applied by nurses rather than a paediatrician.

Methods

The STRONGkids questionnaire was simplified to enhance clarity with nursing staff. Trained nursing staff were asked to apply the tool to children, aged 1 month to 17 years, admitted to the Christchurch Hospital, New Zealand. Each patient was also assessed by a paediatrician. In addition, the current nutritional state of each patient was defined by measuring their weight and height.

Results

Of the 162 children enrolled, 11.7% were undernourished and 13% overnourished. STRONGkids recognised 84% of undernourished children when the tool was applied by nurses and 90% when the tool was applied by a paediatrician, indicating substantial agreement (kappa = 0.65). A minor simplification to the questionnaire improved its utility.

Conclusion

STRONGkids successfully recognised at‐risk children, when applied by either nurses or a paediatrician. It was suitable and feasible for nursing staff to use it to screen for children at risk of nutritional deterioration.
Intellectual disability: novel mutations in DEAF1 cause speech impairment and behavioral problems
Authors: Waltl S.
Published: August 2014

Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems

Vulto‐van Silfhout et al. (2014)

The American Journal of Human Genetics 94(5): 649–661.
DYRK1B variant linked to autosomal dominant metabolic syndrome
Authors: Hickmott J.
Published: August 2014

A form of the metabolic syndrome associated with mutations in DYRK1B

Keramati et al. (2014)

New England Journal of Medicine 370: 1909–1919.
Systemic amyloidosis presenting with glans penis involvement
Authors: Fernandez‐Flores Angel , Castañón‐González Jorge A. , Guerrero‐Ramos Brenda , Castro‐Gaytan Armando , Saeb‐Lima Marcela
Published: August 2014

Penile amyloidosis has been reported on many occasions in the literature, but all of these have been forms of primary cutaneous amyloidosis. Systemic amyloidosis presenting with a penile ulcer as the first manifestation has not previously been reported. We present two patients in whom an ulcer of the glans penis was the first complaint that led to a diagnosis of systemic amyloidosis. In both patients, lambda light chain type amyloid was showed immunohistochemically. Both patients presented with other manifestations of systemic amyloidosis, including nail dystrophy characterized by onycholisis, trachyonychia and onychoschizia.
Sirtuin inhibitor Ex‐527 causes neural tube defects, ventral edema formations, and gastrointestinal malformations in Xenopus laevis embryos
Authors: Ohata Yoshihisa , Matsukawa Shinya , Moriyama Yuki , Michiue Tatsuo , Morimoto Kenta , Sato Yuka , Kuroda Hiroki
Published: August 2014

Chemical reagent Ex‐527 is widely used as a major inhibitor of Sirtuin enzymes, which are a family of highly conserved protein deacetylases and have been linked with caloric restriction and aging by modulating energy metabolism, genomic stability, and stress resistance. However, the extent to which Ex‐527 controls early developmental events of vertebrate embryos remains to be understood. Here, we report an examination of Ex‐527 effects during Xenopus early development, followed by a confirmation of expressions of xSirt1 and xSirt2 in embryonic stages and enhancement of acetylation by Ex‐527. First, we found that reductions in size of neural plate at neurula stages were induced by Ex‐527 treatment. Second, tadpoles with short body length and large edematous swellings in the ventral side were frequently observed. Moreover, Ex‐527‐treated embryos showed severe gastrointestinal malformations in late tadpole stages. Taken together with these results, we conclude that the Sirtuin family start functioning at early embryonic stages and is required for various developmental events.
Sox17 as a candidate regulator of myeloid restricted differentiation potential
Authors: Anani Maha , Nobuhisa Ikuo , Osawa Mitsujiro , Iwama Atsushi , Harada Kaho , Saito Kiyoka , Taga Tetsuya
Published: August 2014

Sry related high mobility group box 17 (Sox17), which is a marker of endodermal cells and a transcriptional regulator, has a critical role in the maintenance of fetal and neonatal hematopoietic stem cells (HSC). Sox17 has been identified as a key regulator of the development and differentiation of fetal hematopoietic progenitors from the aorta‐gonad‐mesonephros (AGM) region. The co‐culture of Sox17‐transduced hematopoietic progenitor cells (CD45lowc‐Kithigh cells) from AGM regions on OP9 stromal cells gives rise to multipotential hematopoietic stem/progenitor cells. Here, we show that in a primary transplantation experiment, Sox17‐transduction in CD45lowc‐Kithigh cells of embryonic day (E) 10.5 AGM increased the absolute number of common myeloid progenitors (CMPs) in the bone marrow (BM) of recipient mice in comparison to that of granulocyte/macrophage progenitors (GMPs) and the megakaryocyte/erythroid progenitors (MEPs). When Sox17‐transduced cells were cultured with OP9 stromal cells, Sox17‐transduced GMPs (Sox17‐GMPs), Sox17‐transduced CMPs (Sox17‐CMPs), and Sox17‐transduced MEPs (Sox17‐MEPs) were generated. Sox17‐GMPs and Sox17‐CMPs maintained their self‐renewal capacity and the hematopoietic ability upon co‐culture with the OP9 stromal cells for some passages. Moreover, Sox17‐GMPs exhibited the increase in expression of c‐Mpl and GATA‐2 in comparison to GMPs of BM and Sox17‐CMPs showed the increase in expression of c‐Mpl, NF‐E2, and β‐globin genes in comparison to CMPs of BM. Furthermore, when Sox17‐transduced cells were cultured in methylcellulose to examine the colony‐forming ability, Sox17‐GMPs and Sox17‐CMPs maintained the formation of mixed colonies for some passages. Taken together, Sox17 is suggested to regulate the maintenance and differentiation of hematopoietic progenitors derived from AGM regions at midgestation, in particular myeloid progenitors.
Skeletal effects of bariatric surgery: examining bone loss, potential mechanisms and clinical relevance
Authors: Scibora L. M.
Published: August 2014

Bariatric surgery is the most effective therapeutic approach to morbid obesity, resulting in substantial weight loss and improved cardiometabolic profiles; however, a growing body of evidence suggests that bariatric procedures increase both skeletal fragility and the risk of related future fracture secondary to excessive bone loss. Prospective evidence shows that areal bone mineral density (BMD) assessed by dual energy X‐ray absorptiometry (DXA) declines by as much as 14% in the proximal femoral regions, including the femoral neck and total hip, 12 months postoperatively. Lumbar spine areal BMD outcomes show greater 12‐month postoperative variability across surgical procedures (−8 to +6%) and contrast with no change in volumetric BMD outcomes measured by quantitative computed tomography. Diminished mechanical loading, micronutrient deficiency and malabsorption, along with neurohormonal alterations, offer plausible underlying mechanisms to explain these observed post‐bariatric bone changes, but most remain largely unsubstantiated in this population. Importantly, DXA‐based skeletal imaging may have limited utility in accurately detecting bone change in people undergoing bariatric surgery; partly because excessive tissue overlying bone increases the variability of areal BMD outcomes. Moreover, a paucity of fracture and osteoporosis incidence data raises questions about whether marked post‐bariatric surgery bone loss is clinically relevant or a functional adaptation to skeletal unloading. Future studies that use technology which is able to accurately capture the site‐specific volumetric BMD and bone architectural changes that underpin bone strength in people undergoing bariatric surgery, that consider mechanical load, and that better quantify long‐term fracture and osteoporosis incidence are necessary to understand the actual skeletal effects of bariatric surgery.
WONOEP appraisal: New genetic approaches to study epilepsy
Authors: Rossignol Elsa , Kobow Katja , Simonato Michele , Loeb Jeffrey A. , Grisar Thierry , Gilby Krista L. , Vinet Jonathan , Kadam Shilpa D. , Becker Albert J.
Published: August 2014

New genetic investigation techniques, including next‐generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming, and optogenetic manipulations within epileptic networks are progressively unraveling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiologic effects of mutations in epilepsy‐associated genes on a multilayer level, from cells to circuits. This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy (WONOEP 2013) in Quebec, Canada. Next‐generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and has revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knock‐down approaches, are enabling functional validation with exquisite cell‐type and temporal specificity. In addition, optogenetics, using cell‐type–specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. In addition, genetically encoded cell‐type labeling is providing new means to assess the role of the nonneuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next‐generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and noncoding ribonucleic acid (RNA) involved in modifying gene expression following seizures. In addition, genetically based bioluminescent reporters are providing new opportunities to assess neuronal activity and neurotransmitter levels both in vitro and in vivo in the context of epilepsy. Finally, genetically rederived neurons generated from patient induced pluripotent stem cells and genetically modified zebrafish have become high‐throughput means to investigate disease mechanisms and potential new therapies. Genetics has changed the field of epilepsy research considerably, and is paving the way for better diagnosis and therapies for patients with epilepsy.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Long‐term maintenance of skin immune system in a NOD‐Scid IL2rγnull mouse model transplanted with human skin
Authors: Soria Angèle , Boccara David , Chonco Louis , Yahia Nora , Dufossée Mélody , Cardinaud Sylvain , Moris Arnaud , Liard Christelle , Joulin‐Giet Alix , Julithe Marion , Mimoun Maurice , Combadière Béhazine , Perrin Hélène
Published: August 2014

We developed a NOD‐Scid IL2rγnull mouse model transplanted with human skin that brings fundamental insight on in vivo cellular mechanisms of intradermal immunization and antigen presentation by dermal dendritic and epidermal Langerhans cells for skin T‐cell immunity. Indeed, T‐cell immunity is a crucial checkpoint for the induction of in vivo rapid control of skin infection. With the long‐term preservation of a complete human skin immune system, this model offers the unique opportunity not only to better understand mechanisms of skin immune response but also to test new compounds and devices for cutaneous routes of vaccination, as well as new therapeutics approach for skin diseases, allergies or infections.
Role of epidermal γδ T‐cell‐derived interleukin 13 in the skin‐whitening effect of Ginsenoside F1
Authors: Han Jiyeon , Lee Eunkyung , Kim EunJoo , Yeom Myung Hun , Kwon Ohsang , Yoon Tae Hong , Lee Tae Ryong , Kim Kwangmi
Published: August 2014

Ginsenoside F1 (GF1) is a metabolite of ginsenoside Rg1. Although GF1 has several benefits for skin physiology, the effect of GF1 on skin pigmentation has not been reported. We found that a cream containing 0.1% GF1 showed a significant whitening effect on artificially tanned human skin after 8 weeks of application. However, GF1 did not inhibit mRNA expression of tyrosinase or dopachrome tautomerase (DCT) in normal human epidermal melanocytes (NHEMs) or cocultured NHEMs/normal human epidermal keratinocytes. Interestingly, GF1 enhanced production of interleukin 13 (IL‐13) from human epidermal γδ T cells. IL‐13 significantly reduced the mRNA expression and protein amount of both tyrosinase and DCT and reduced melanin synthesis activities in NHEMs, resulting in visible brightening of NHEM pellet. These results suggest that enhancement of IL‐13 production by GF1 from epidermal γδ T cells might play a role in the skin‐whitening effect of GF1 via the suppression of tyrosinase and DCT.
The dynamics of architectural complexity on coral reefs under climate change
Authors: Bozec Yves‐Marie , Alvarez‐Filip Lorenzo , Mumby Peter J.
Published: August 2014

One striking feature of coral reef ecosystems is the complex benthic architecture which supports diverse and abundant fauna, particularly of reef fish. Reef‐building corals are in decline worldwide, with a corresponding loss of live coral cover resulting in a loss of architectural complexity. Understanding the dynamics of the reef architecture is therefore important to envision the ability of corals to maintain functional habitats in an era of climate change. Here, we develop a mechanistic model of reef topographical complexity for contemporary Caribbean reefs. The model describes the dynamics of corals and other benthic taxa under climate‐driven disturbances (hurricanes and coral bleaching). Corals have a simplified shape with explicit diameter and height, allowing species‐specific calculation of their colony surface and volume. Growth and the mechanical (hurricanes) and biological erosion (parrotfish) of carbonate skeletons are important in driving the pace of extension/reduction in the upper reef surface, the net outcome being quantified by a simple surface roughness index (reef rugosity). The model accurately simulated the decadal changes of coral cover observed in Cozumel (Mexico) between 1984 and 2008, and provided a realistic hindcast of coral colony‐scale (1–10 m) changing rugosity over the same period. We then projected future changes of Caribbean reef rugosity in response to global warming. Under severe and frequent thermal stress, the model predicted a dramatic loss of rugosity over the next two or three decades. Critically, reefs with managed parrotfish populations were able to delay the general loss of architectural complexity, as the benefits of grazing in maintaining living coral outweighed the bioerosion of dead coral skeletons. Overall, this model provides the first explicit projections of reef rugosity in a warming climate, and highlights the need of combining local (protecting and restoring high grazing) to global (mitigation of greenhouse gas emissions) interventions for the persistence of functional reef habitats.
Endodontic complications in teeth with vital pulps restored with composite resins: a systematic review
Authors: Dawson V. S. , Amjad S. , Fransson H.
Published: August 2014

Composite resin is used extensively for restoration of teeth with vital pulps. Although cell culture studies have disclosed harmful effects on pulpal cells, any untoward clinical effects, manifest as adverse pulpal responses, have yet to be determined. This study comprises a systematic review, designed to address the question of whether the risk of endodontic complications is greater with composite resin restorations than with other restorative materials, such as amalgam. The study methodology involved (i) formulation of the research question, (ii) construction and conduct of an extensive literature search with (iii) interpretation and assessment of the retrieved literature. A search of the medical database PubMed was complemented with a search of the Controlled Trials Register (CENTRAL). The initial search yielded 1043 publications, the abstracts of which were read independently by the authors. After additional searches, 10 studies were included in the review. In all the included studies, the level of evidence was assessed as low. No conclusions could therefore be drawn. The included studies reported few, if any, endodontic complications. Little or no differences emerged between teeth restored with composite resins and those restored with amalgam. To determine whether composite resin restorations of teeth with vital pulps are associated with an increased risk for development of endodontic complications such as apical periodontitis, further evidence is needed, from well‐constructed studies with a large number of participants.
LL37 induces VEGF expression in dental pulp cells through ERK signalling
Authors: Khung R. , Shiba H. , Kajiya M. , Kittaka M. , Ouhara K. , Takeda K. , Mizuno N. , Fujita T. , Komatsuzawa H. , Kurihara H.
Published: August 2014

Aim

To examine the in vitro effects of LL37 on the expression of vascular endothelial growth factor (VEGF) in human pulp cells and to identify the intracellular signalling pathway involved.

Methodology

Pulp cells at passage 6 were treated with 10 μg mL−1 synthesized LL37, and an inhibition assay was performed with MAPK or NF‐κB inhibitors to determine the possible signalling pathway. VEGF mRNA, VEGF protein and phosphorylated ERK1/2 levels were determined by real‐time PCR, ELISA and Western blot, respectively. Data were analysed using t‐tests.

Results

LL37 significantly increased both the mRNA and protein levels of VEGF in pulp cells (P < 0.01). However, pre‐treatment with an ERK kinase inhibitor suppressed these increases. Furthermore, the inhibitor blocked LL37‐induced ERK1/2 phosphorylation.

Conclusions

LL37 activated the ERK pathway to boost VEGF secretion from human pulp cells. Because of this angiogenic effect and its reported induction of pulp cell migration and antimicrobial activity against cariogenic bacteria, LL37 may be applicable as a pulp capping material.
Immunoexpression of tryptase‐positive mast cells in periapical granulomas and radicular cysts
Authors: Costa Neto H. , de Andrade A. L. D. L. , Gordón‐Núñez M. A. , Freitas R. de A. , Galvão H. C.
Published: August 2014

Aim

To evaluate and compare the immunoexpression of tryptase in samples of periapical granulomas (PGs) and radicular cysts (RCs) correlating it with the type of lesion, localization, intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining, in order to gain insight into the phlogistic role of these cells in the lesions studied.

Methodology

Twenty‐five PGs and twenty‐five RCs obtained from human teeth without endodontic treatment were submitted to morphological and immunohistochemical analysis using anti‐tryptase antibody. Mast cells were identified and counted in three regions: intra‐epithelial, central/superficial and deep portions. The data were analysed using the Mann–Whitney U‐test (P < 0.05).

Results

In comparison with RCs, PGs exhibited higher immunoexpression of tryptase‐positive mast cells located in both central/superficial and deep regions (P < 0.001 and P < 0.001, respectively). When considering the total number of mast cells and disregarding the location, the number of tryptase‐positive mast cells increased gradually from RCs to PGs (P < 0.001). Lesions with inflammatory infiltrate grade III had greater number of tryptase‐positive mast cells located in both central/superficial and deep regions than lesions with inflammatory infiltrates grade II (P = 0.045 and P = 0.025). When the location was ignored, the lesions with inflammatory infiltrate grade III also exhibited higher immunostaining of tryptase‐positive mast cells (P = 0.01).

Conclusions

Tryptase‐positive mast cells were present in chronic periapical lesions in a larger number in periapical granulomas than in radicular cysts, in both central/superficial and deep regions.
Crack Initiation Tendency of Chemically Strengthened Glasses
Authors: Morozumi Hidekatsu , Nakano Hirotaka , Yoshida Satoshi , Matsuoka Jun
Published: August 2014

The relationship between crack initiation tendency before chemical strengthening and fracture strength of chemically strengthened glass was investigated. Four kinds of glass compositions were used in this study: soda‐lime silicate (SLS), aluminosilicate (ALS‐1,ALS‐2), and aluminoborosilicate (ALBS) glasses. The fracture strength of sheet glass was measured by the four‐point bending test, the ring‐on‐ring test, the ball drop test, and the predamaged four‐point bending test.ALBSglass, which has the lowest crack formation probability before chemical strengthening, is more damage tolerant than other glasses, and one of the best candidates for chemical strengthening.