bluuebunny/crossref_metadata_2025 huggingface dataset:
Oropharyngeal cancer: United Kingdom National Multidisciplinary Guidelines
Authors: Mehanna H , Evans M , Beasley M , Chatterjee S , Dilkes M , Homer J , O'Hara J , Robinson M , Shaw R , Sloan P
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. There has been significant debate in the management of oropharyngeal cancer in the last decade, especially in light of the increased incidence, clarity on the role of the human papilloma virus in this disease and the treatment responsiveness of the human papilloma virus positive cancers. This paper discusses the evidence base pertaining to the management of oropharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care.

Recommendations

• Cross-sectional imaging is required in all cases to complete assessment and staging. (R)

• Magnetic resonance imaging is recommended for primary site and computed tomography scan for neck and chest. (R)

• Positron emission tomography combined with computed tomography scanning is recommended for the assessment of response after chemoradiotherapy, and has a role in assessing recurrence. (R)

• Examination under anaesthetic is strongly recommended, but not mandatory. (R)

• Histological diagnosis is mandatory in most cases, especially for patients receiving treatment with curative intent. (R)

• Oropharyngeal carcinoma histopathology reports should be prepared according to The Royal College of Pathologists Guidelines. (G)

• Human papilloma virus (HPV) testing should be carried out for all oropharyngeal squamous cell carcinomas as recommended in The Royal College of Pathologists Guidelines. (R)

• Human papilloma virus testing for oropharyngeal cancer should be performed within a diagnostic service where the laboratory procedures and reporting standards are quality assured. (G)

• Treatment options for T1–T2 N0 oropharyngeal squamous cell carcinoma include radical radiotherapy or transoral surgery and neck dissection (with post-operative (chemo)radiotherapy if there are adverse pathological features on histological examination). (R)

• Transoral surgery is preferable to open techniques and is associated with good functional outcomes in retrospective series. (R)

• If treated surgically, neck dissection should include levels II–IV and possibly level I. Level IIb can be omitted if there is no disease in level IIa. (R)

• If treated with radiotherapy, levels II–IV should be included, and possibly level Ib in selected cases. (R)

• Altering the modalities of treatment according to HPV status is currently controversial and should be undertaken only in clinical trials. (R)

• Where possible, patients should be offered the opportunity to enrol in clinical trials in the field. (G)
Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines
Authors: Mackenzie K , Watson M , Jankowska P , Bhide S , Simo R
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the evidence base pertaining to the management of metastatic neck disease in the setting of an unknown primary and provides recommendations on the work up and management for this group of patients receiving cancer care.

Recommendations

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All patients presenting with confirmed cervical lymph node metastatic squamous cell carcinoma and no apparent primary site should undergo:

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Positron emission tomography-computed tomography whole-body scan. (R)

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Panendoscopy and directed biopsies. (R)

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Bilateral tonsillectomy. (R)

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Tongue base mucosectomy can be offered if facilities and expertise exists. (G)

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Concomitant chemotherapy with radiation should be considered in patients with an unknown primary. (R)

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Concomitant chemotherapy with radiation should be offered to suitable patients in the post-operative setting, where indicated. (R)

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Neo-adjuvant chemotherapy can be used in gross ‘unresectable’ disease. (R)

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Patients should be followed up at least two months in the first two years and three to six months in the subsequent years. (G)

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Patients should be followed up to a minimum of five years with a prolonged follow up for selected patients. (G)

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Positron emission tomography–computed tomography scan at three to four months after treatment is a useful follow-up strategy for patients treated by chemoradiation therapy. (R)
Reconstructive considerations in head and neck surgical oncology: United Kingdom National Multidisciplinary Guidelines
Authors: Ragbir M , Brown J S , Mehanna H
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. The reconstructive needs following ablative surgery for head and neck cancer are unique and require close attention to both form and function. The vast experience accrued with microvascular reconstructive surgery has meant a significant expansion in the options available. This paper discusses the options for reconstruction available following ablative surgery for head and neck cancer and offers recommendations for reconstruction in the various settings.

Recommendations

• Microsurgical free flap reconstruction should be the primary reconstructive option for most defects of the head and neck that need tissue transfer. (R)

• Free flaps should be offered as first choice of reconstruction for all patients needing circumferential pharyngoesophageal reconstruction. (R)

• Free flap reconstruction should be offered for patients with class III or higher defects of the maxilla. (R)

• Composite free tissue transfer should be offered as first choice to all patients needing mandibular reconstruction. (R)

• Patients undergoing salvage total laryngectomy should be offered vascularised flap reconstruction to reduce pharyngocutaneous fistula rates. (R)
Palliative and supportive care in head and neck cancer: United Kingdom National Multidisciplinary Guidelines
Authors: Cocks H , Ah-See K , Capel M , Taylor P
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It provides recommendations on the assessments and interventions for this group of patients receiving palliative and supportive care.

Recommendations

• Palliative and supportive care must be multidisciplinary. (G)

• All core team members should have training in advanced communication skills. (G)

• Palliative surgery should be considered in selected cases. (R)

• Hypofractionated or short course radiotherapy should be considered for local pain control and for painful bony metastases. (R)

• All palliative patients should have a functional endoscopic evaluation of swallowing (FEES) assessment of swallow to assess for risk of aspiration. (G)

• Pain relief should be based on the World Health Organization pain ladder. (R)

• Specialist pain management service involvement should be considered early for those with refractory pain. (G)

• Constipation should be avoided by the judicious use of prophylactic laxatives and the correction of systemic causes such as dehydration, hypercalcaemia and hypothyroidism. (G)

• Organic causes of confusion should be identified and corrected where appropriate, failing this, treatment with benzodiazepines or antipsychotics should be considered. (G)

• Patients with symptoms suggestive of spinal metastases or metastatic cord compression must be managed in accordance with the National Institute for Health and Care Excellence guidance. (R)

• Cardiopulmonary resuscitation is inappropriate in the palliative dying patient. (R)

• ‘Do not attempt cardiopulmonary resuscitation’ orders should be completed and discussed with the patient and/or the family unless good reasons exist not to do so where appropriate. This is absolutely necessary when a patient's care is to be managed at home. (G)
The clinical nurse specialist's role in head and neck cancer care: United Kingdom National Multidisciplinary Guidelines
Authors: Dempsey L , Orr S , Lane S , Scott A
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the role of the clinical nurse specialist in the head and neck cancer patient journey and provides recommendations on the clinical nurse specialist led assessments and interventions for this group of patients receiving cancer care.

Recommendations

• All cancer patients should meet a clinical nurse specialist at the point of diagnosis. (R)

• Clinical nurse specialists must act as gate keeper to the patients' cancer pathway to provide a seamless journey. (R)

• Holistic needs assessment should be completed at different stages of the patient's pathway to reflect the changes of the patients' needs. (R)

• Clinical nurse specialists to be part of local and national initiatives for health promotion and raising awareness in the public domain. (G)

• Clinical nurse specialists should lead in redesigning of services and policies to ensure they are responsive to patient's needs for the future. (G)

• Treatment summaries should become part of practice to provide good communication between primary and secondary care to enable continuity of care for the patient. (G)
Organisation and provision of head and neck cancer surgical services in the United Kingdom: United Kingdom National Multidisciplinary Guidelines
Authors: Stafford F , Ah-See K , Fardy M , Fell K
Published: May 2016

This is the official guideline endorsed by the surgical specialty associations involved in the care of head and neck cancer patients in the UK. This paper summarises the current state of play in the organisation and provision of head and neck cancer surgical services in the UK.
Chemotherapy: United Kingdom National Multidisciplinary Guidelines
Authors: Kelly C G
Published: May 2016

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper summarises the role of chemotherapy in head and neck cancer management, recent advances and what the future holds for this modality.
Exploring drivers and deterrents of the illegal consumption and trade of marine turtle products in Cape Verde, and implications for conservation planning
Authors: Hancock Joana M. , Furtado Safiro , Merino Sonia , Godley Brendan J. , Nuno Ana
Published: May 2016

Conservation regulations aimed at restricting resource use are commonly used to manage and protect natural resources but their implementation depends on the compliance of resource users. The design of effective regulations should be informed by an understanding of the factors that affect compliance, considering contextual socio-economic information. Changes have been implemented in the national legislation protecting marine turtles in the Cape Verde archipelago, where historical and recent records indicate heavy human predation pressure on nesting and foraging marine turtles. We present an assessment of levels of illegal harvesting and consumption of marine turtle products on two of the islands, Boa Vista and Santiago, and an analysis of their potential drivers. Key stakeholders were interviewed to investigate the perceived impact of the main interventions employed in Cape Verde to reduce illegal harvesting, trade and consumption of marine turtles. Despite an apparent decrease in harvesting and consumption, our results suggest there has been a shift from subsistence harvesting to trade in Boa Vista. The existence of laws to protect marine turtles was perceived as a deterrent to harvesting, and awareness campaigns and a lack of availability were perceived as reasons for the decrease in consumption in Boa Vista and Santiago, respectively. Aiming to inform ongoing discussions, we recommend a multi-targeted approach focusing on both suppliers and consumers to magnify conservation effectiveness. Regular impact evaluation focusing on harvest and consumption is needed to improve the design of regulations and inform policy decision making.
Situating the Debate on “Geometrical Algebra” within the Framework of Premodern Algebra
Authors: Sialaros Michalis , Christianidis Jean
Published: May 2016

Argument

The aim of this paper is to employ the newly contextualized historiographical category of “premodern algebra” in order to revisit the arguably most controversial topic of the last decades in the field of Greek mathematics, namely the debate on “geometrical algebra.” Within this framework, we shift focus from the discrepancy among the views expressed in the debate to some of the historiographical assumptions and methodological approaches that the opposing sides shared. Moreover, by using a series of propositions related toElem.II.5 as a case study, we discuss Euclid's geometrical proofs, the so-called “semi-algebraic” alternative demonstrations attributed to Heron of Alexandria, as well as the solutions given by Diophantus, al-Sulamī, and al-Khwārizmī to the corresponding numerical problem. This comparative analysis offers a new reading of Heron's practice, highlights the significance of contextualizing “premodern algebra,” and indicates that the origins of algebraic reasoning should be sought in the problem-solving practice, rather than in the theorem-proving tradition.
Copernicus's Publication Strategy in the Contexts of Imperial and Papal Censorship and of Warmian Diplomatic Precedents
Authors: Blumenthal Geoffrey
Published: May 2016

Argument

The main thesis of this paper is that Copernicus's avoidance of all admission that scripture was contravened inDe revolutionibusand his composition of its new Preface in 1542, as well as the non-publication of Rheticus'sTreatise on Holy Scripture and the Motion of the Earth, were influenced by the early information they received on the failure of the 1541 Regensburg Protestant-Catholic colloquy, among the major consequences of which were significant increases in the problems concerning publishing works which contravened scripture. This is supported by examining Rheticus's first letter to Paul Eber in conjunction with the documents on the Regensburg colloquy and on censorship in Nuremberg, as well as with the existing literature on Copernicus and his context. In view of the main thesis, Copernicus's apparent dedication of the work to the Pope merits additional explanation, and the second thesis is that components of explanations for several aspects of those parts of the Preface that relate to the Papacy and to theologians can be provided via comparisons with previous diplomacy between Warmia and the Papacy which occurred or was being referred to during Copernicus's time. This is supported by examining these parts of the Preface in the light of a selection of the relevant documents.
On spaces of commuting elements in Lie groups
Authors: COHEN FREDERICK R. , STAFA MENTOR
Published: May 2016

The main purpose of this paper is to introduce a method to “stabilise” certain spaces of homomorphisms from finitely generated free abelian groups to a Lie groupG, namely Hom(ℤn,G). We show that this stabilised space of homomorphisms decomposes after suspending once with “summands” which can be reassembled, in a sense to be made precise below, into the individual spaces Hom(ℤn,G) after suspending once. To prove this decomposition, a stable decomposition of an equivariant function space is also developed. One main result is that the topological space of all commuting elements in a compact Lie group is homotopy equivalent to an equivariant function space after inverting the order of the Weyl group. In addition, the homology of the stabilised space admits a very simple description in terms of the tensor algebra generated by the reduced homology of a maximal torus in favorable cases. The stabilised space also allows the description of the additive reduced homology of the individual spaces Hom(ℤn,G), with the order of the Weyl group inverted.
The influence of practice culture on designed artefacts
Authors: Schmidt Robert , Dainty Andy
Published: May 2016

Design can be viewed as a complex and on-going social accomplishment, a product of everyday trajectories between a milieu of human and material registers. Seen in this way the design practice serves as an arena for these quotidian activities. We seek to construct a more dynamic picture of architecture by connecting process and product, supplementing a project narrative with one of practice, highlighting the context in which the outcome was created. We address the research question: how does practice culture become intertwined within the designed product?

A research model emerged from the review of the literature and evolved as a loose framework to discuss the practices and projects at hand. The research focused on the particular design consideration of adaptability in an effort to direct and ground the study. The research was conducted in two stages –at first a set of interviews were conducted to gain broader insights into the everyday accounts of the practices and secondly, project case studies were selected to further investigate the topic.

The narratives reveal the culture of each practice to stress a particular meaning in each context: for Make it is about a beautiful object; for ABA a piece of social infrastructure and; for CGL a business asset. Adaptability finds itself subdued, promoted, compromised and sold as part of the design process and the resultant architecture. Our contribution extends the argument that design is entangled within its socio-cultural surroundings and grounds the culture of practice in the designed artefacts - the way in which a practice handles decision-making contingencies, both endogenous and exogenous forces, will together shape a practice disposition towards design (adaptability). Design that is driven by a strong culture that embeds exogenous influences in the approach tends to provide more adaptable solutions as part of a quest to satisfy long-term, societal concerns.
Going global: Indian adolescents’ eating patterns
Authors: Shaikh Nida I , Patil Shailaja S , Halli Shiva , Ramakrishnan Usha , Cunningham Solveig A
Published: May 2016

Objective

To describe adolescents’ eating patterns of traditional, global/non-local and mixed foods, and the factors that may influence food consumption, access and preferences, in a globalizing city.

Design

A representative sample of school-going adolescents completed a cross-sectional survey including an FFQ designed to identify traditional and global foods. Student’sttest and ordinal logistic regression were used to examine weekly food intake, including differences between boys and girls and between adolescents attending private and public schools.

Setting

Vijayapura city, Karnataka State, India.

Subjects

Adolescents (n399) aged 13–16 years.

Results

Compared with dietary guidelines, adolescents consumed fruit, green leafy vegetables, non-green leafy vegetables and dairy less frequently than recommended and consumed energy-dense foods more frequently than recommended. Traditional but expensive foods (fruits, dairy, homemade sweets and added fat) were more frequently consumed by private-school students, generally from wealthier, more connected families, than by public-school students; the latter more frequently consumed both traditional (tea, coffee, eggs) and mixed foods (snack and street foods;P≤0·05). Girls reported more frequent consumption of global/non-local packaged and ready-to-eat foods, non-green leafy vegetables and added fat than boys (P≤0·05). Boys reported more frequent consumption of eggs and street foods than girls (P≤0·05).

Conclusions

Adolescents’ eating patterns in a globalizing city reflect a combination of global/non-local and traditional foods, access and preferences. As global foods continue to appear in low- and middle-income countries, understanding dietary patterns and preferences can inform efforts to promote diversity and healthfulness of foods.
„Allein oder mit anderen?“
Authors: Sparfeldt Jörn R. , Lotz Christin , Sapp Sarah , Rost Detlef H.
Published: May 2016

Zusammenfassung. Soziale Selbstkonzepte gelten als bedeutsam; ihre Erfassung stellt bei Leseanfängerinnen und Leseanfängern eine Herausforderung dar. Erfolgversprechend könnte eine bildbasierte Selbstkonzepterfassung sein. Daher wurde der Bildertest zum sozialen Selbstkonzept (BSSK) von Langfeldt und Prücher (2004) bei N = 320 Kindern der 2. Klassenstufe überprüft. Die psychometrischen Kennwerte waren mit denen des Manuals weitgehend vergleichbar, faktorenanalytisch wies ein Generalfaktormodell eine gute Modellanpassung auf. Der BSSK korrelierte gering mit der Peer Relation Scale des SDQ-I von Marsh (1992) . Die Präsentation im Originalformat (pro Item ein Bildpaar, wobei ein Bild auszuwählen war) und die Präsentation einzelner BSSK-Bilder mit fünfstufigem Antwortformat ergaben vergleichbare Zusammenhänge mit der Peer Relation Scale. Eine Instruktionsmanipulation (gewünschtes Verhalten statt tatsächliches Verhalten) ergab höhere Mittelwerte und vergleichbare Skalenzusammenhänge. Der Nutzen einer bildbasierten Erfassung des sozialen Selbstkonzepts bei Grundschulkindern wird diskutiert.
Die Facettenstruktur des Big Five Inventory (BFI)
Authors: Rammstedt Beatrice , Danner Daniel
Published: May 2016

Zusammenfassung. Die für die angloamerikanische Version des Big Five Inventory (BFI) entwickelte und validierte Facettenstruktur ( Soto & John, 2009 ) wurde für die deutsche Adaptation des BFI übertragen und auf ihre Angemessenheit geprüft. Basierend auf drei umfangreichen Stichproben – einer studentischen, einer bildungsheterogenen Stichprobe und einer bevölkerungsrepräsentativen Zufallsstichprobe – konnte gezeigt werden, dass die 10 Facetten des deutschen BFI substantielle und mit der angloamerikanischen Version vergleichbare Reliabilitäten und Konvergenzen zwischen Selbst- und Bekanntenurteil und mit den entsprechenden Facetten und Globalskalen des NEO-PI-R (NEO-Personality Inventory) und NEO-FFI (NEO-Five Factor Inventory) aufweisen. Ferner konnte eine diskriminante Validität zu den jeweils anderen Facetten der gleichen sowie zu den Facetten der anderen Big Five Dimensionen gezeigt werden. Die Nützlichkeit der Verwendung dieser Facetten, zusätzlich zu den Globalskalen, wurde durch deren spezifische Zusammenhänge mit verschiedenen soziodemografischen und Einstellungsmerkmalen nachgewiesen. Insofern existiert auch für den deutschen Sprachraum ein ökonomisches Maß, um spezifischere Persönlichkeitsaspekte abzubilden.
Entwicklung und Validierung eines Fragebogens zur Erfassung multipler Selbstkonzeptfacetten bei Förderschülern (Schwerpunkt Lernen) und Regelschülern der Sekundarstufe I
Authors: Weber Kira Elena , Freund Philipp Alexander
Published: May 2016

Zusammenfassung. Im vorliegenden Beitrag wird die Entwicklung und Validierung eines deutschsprachigen Messinstruments zur Erfassung des Selbstkonzepts bei Jugendlichen der Sekundarstufe I beschrieben. In Anlehnung an die deutsche Version des Self Description Questionnaire I (SDQ I) von Arens, Trautwein und Hasselhorn (2011) wurden 8 Skalen mit insgesamt 38 Items entwickelt. Diese sollten multiple Selbstkonzeptfacetten ökonomisch erfassen und sowohl in Gymnasien, Real-, Haupt-, Gesamt- als auch in Förderschulen (Schwerpunkt Lernen) einsetzbar sein. Es wurden Testanalysen auf der Datenbasis einer Gesamtstichprobe von N = 1 907 Schülerinnen und Schülern verschiedener Schulformen (n = 294 Förderschülerinnen und -schüler) durchgeführt. Konfirmatorische Faktorenanalysen bestätigten die postulierte achtfaktorielle Struktur. Die Messinvarianz über Geschlecht und Schulform konnte belegt werden. Wesentliche Befunde internationaler Studien zur Struktur des Selbstkonzepts konnten mit dem Fragebogen repliziert werden. Zusammenhänge mit Außenkriterien wiesen auf eine zufriedenstellende Validität der Selbstkonzeptskalen hin. Die Reliabilitätsschätzungen fielen allgemein gut aus (α = .84–.91).
Stalled replication forks within heterochromatin require ATRX for protection
Authors: Huh M S , Ivanochko D , Hashem L E , Curtin M , Delorme M , Goodall E , Yan K , Picketts D J
Published: May 2016

Expansive growth of neural progenitor cells (NPCs) is a prerequisite to the temporal waves of neuronal differentiation that generate the six-layered neocortex, while also placing a heavy burden on proteins that regulate chromatin packaging and genome integrity. This problem is further reflected by the growing number of developmental disorders caused by mutations in chromatin regulators. ATRX gene mutations cause a severe intellectual disability disorder (α-thalassemia mental retardation X-linked (ATRX) syndrome; OMIM no. 301040), characterized by microcephaly, urogenital abnormalities and α-thalassemia. Although the ATRX protein is required for the maintenance of repetitive DNA within heterochromatin, how this translates to disease pathogenesis remain poorly understood and was a focus of this study. We demonstrate that AtrxFoxG1Cre forebrain-specific conditional knockout mice display poly(ADP-ribose) polymerase-1 (Parp-1) hyperactivation during neurogenesis and generate fewer late-born Cux1- and Brn2-positive neurons that accounts for the reduced cortical size. Moreover, DNA damage, induced Parp-1 and Atm activation is elevated in progenitor cells and contributes to their increased level of cell death. ATRX-null HeLa cells are similarly sensitive to hydroxyurea-induced replication stress, accumulate DNA damage and proliferate poorly. Impaired BRCA1-RAD51 colocalization and PARP-1 hyperactivation indicated that stalled replication forks are not efficiently protected. DNA fiber assays confirmed that MRE11 degradation of stalled replication forks was rampant in the absence of ATRX or DAXX. Indeed, fork degradation in ATRX-null cells could be attenuated by treatment with the MRE11 inhibitor mirin, or exacerbated by inhibiting PARP-1 activity. Taken together, these results suggest that ATRX is required to limit replication stress during cellular proliferation, whereas upregulation of PARP-1 activity functions as a compensatory mechanism to protect stalled forks, limiting genomic damage, and facilitating late-born neuron production.
Deep-reaching thermocline mixing in the equatorial pacific cold tongue
Authors: Liu Chuanyu , Köhl Armin , Liu Zhiyu , Wang Fan , Stammer Detlef
Published: May 2016

Vertical mixing is an important factor in determining the temperature, sharpness and depth of the equatorial Pacific thermocline, which are critical to the development of El Ninõ and Southern Oscillation (ENSO). Yet, properties, dynamical causes and large-scale impacts of vertical mixing in the thermocline are much less understood than that nearer the surface. Here, based on Argo float and the Tropical Ocean and Atmosphere (TAO) mooring measurements, we identify a large number of thermocline mixing events occurring down to the lower half of the thermocline and the lower flank of the Equatorial Undercurrent (EUC), in particular in summer to winter. The deep-reaching mixing events occur more often and much deeper during periods with tropical instability waves (TIWs) than those without and under La Niña than under El Niño conditions. We demonstrate that the mixing events are caused by lower Richardson numbers resulting from shear of both TIWs and the EUC.
Rho-kinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs
Authors: Sharanek Ahmad , Burban Audrey , Burbank Matthew , Le Guevel Rémy , Li Ruoya , Guillouzo André , Guguen-Guillouzo Christiane
Published: May 2016

Intrahepatic cholestasis represents a frequent manifestation of drug-induced liver injury; however, the mechanisms underlying such injuries are poorly understood. In this study of human HepaRG and primary hepatocytes, we found that bile canaliculi (BC) underwent spontaneous contractions, which are essential for bile acid (BA) efflux and require alternations in myosin light chain (MLC2) phosphorylation/dephosphorylation. Short exposure to 6 cholestatic compounds revealed that BC constriction and dilation were associated with disruptions in the ROCK/MLCK/myosin pathway. At the studied concentrations, cyclosporine A and chlorpromazine induced early ROCK activity, resulting in permanent MLC2 phosphorylation and BC constriction. However, fasudil reduced ROCK activity and caused rapid, substantial and permanent MLC2 dephosphorylation, leading to BC dilation. The remaining compounds (1-naphthyl isothiocyanate, deoxycholic acid and bosentan) caused BC dilation without modulating ROCK activity, although they were associated with a steady decrease in MLC2 phosphorylation via MLCK. These changes were associated with a common loss of BC contractions and failure of BA clearance. These results provide the first demonstration that cholestatic drugs alter BC dynamics by targeting the ROCK/MLCK pathway; in addition, they highlight new insights into the mechanisms underlying bile flow failure and can be used to identify new predictive biomarkers of drug-induced cholestasis.
Hepatocellular carcinoma: thyroid hormone promotes tumorigenicity through inducing cancer stem-like cell self-renewal
Authors: Wang Tao , Xia Lei , Ma Sicong , Qi Xingxing , Li Qigen , Xia Yun , Tang Xiaoyin , Cui Dan , Wang Zhi , Chi Jiachang , Li Ping , Feng Yu-xiong , Xia Qiang , Zhai Bo
Published: May 2016

Cancer stem-like cells (CSCs) play a key role in maintaining the aggressiveness of hepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs is unclear. In the study, we report that thyroid hormone (TH) promotes cell self-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cells and promotes drug resistance of HCC cells. By analyzing primary human HCC samples, we found that TRα transcript level is significantly elevated in primary liver cancer and portal vein metastatic tumor, compared to that of adjacent normal liver tissue. Knocking down TRα not only inhibits HCC self-renewal in vitro but also suppresses HCC tumor growth in vivo. Interestingly, treatment of TH leads to activation of NF-κB, which is required for the function of TH on inducing HCC cell self-renewal. We also found TRα and p65 cooperatively drive the expression of BMI1 by co-binding to the promoter region of BMI1 gene. In summary, our study uncovers a novel function of TH signaling in regulating the CSCs of HCC and these findings might be useful for developing novel therapies by targeting TH function in HCC cells.
Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke
Authors: Van Kanegan Michael J. , Dunn Denise E. , Kaltenbach Linda S. , Shah Bijal , He Dong Ning , McCoy Daniel D. , Yang Peiying , Peng Jiangnan , Shen Li , Du Lin , Cichewicz Robert H. , Newman Robert A. , Lo Donald C.
Published: May 2016

We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0–4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0–4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer’s disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.
Differential expression profiles and pathways of genes in sugarcane leaf at elongation stage in response to drought stress
Authors: Li Changning , Nong Qian , Solanki Manoj Kumar , Liang Qiang , Xie Jinlan , Liu Xiaoyan , Li Yijie , Wang Weizan , Yang Litao , Li Yangrui
Published: May 2016

Water stress causes considerable yield losses in sugarcane. To investigate differentially expressed genes under water stress, a pot experiment was performed with the sugarcane variety GT21 at three water-deficit levels (mild, moderate and severe) during the elongation stage and gene expression was analyzed using microarray technology. Physiological parameters of sugarcane showed significant alterations in response to drought stress. Based on the expression profile of 15,593 sugarcane genes, 1,501 (9.6%) genes were differentially expressed under different water-level treatments; 821 genes were upregulated and 680 genes were downregulated. A gene similarity analysis showed that approximately 62.6% of the differentially expressed genes shared homology with functional proteins. In a Gene Ontology (GO) analysis, 901 differentially expressed genes were assigned to 36 GO categories. Moreover, 325 differentially expressed genes were classified into 101 pathway categories involved in various processes, such as the biosynthesis of secondary metabolites, ribosomes, carbon metabolism, etc. In addition, some unannotated genes were detected; these may provide a basis for studies of water-deficit tolerance. The reliability of the observed expression patterns was confirmed by RT-PCR. The results of this study may help identify useful genes for improving drought tolerance in sugarcane.
Structural investigation into physiological DNA phosphorothioate modification
Authors: Lan Wenxian , Hu Zhongpei , Shen Jie , Wang Chunxi , Jiang Feng , Liu Huili , Long Dewu , Liu Maili , Cao Chunyang
Published: May 2016

DNA phosphorothioate (PT) modification, with sulfur replacing a nonbridging phosphate oxygen in a sequence and stereo specific manner, is a novel physiological variation in bacteria. But what effects on DNA properties PT modification has is still unclear. To address this, we prepared three double-stranded (ds) DNA decamers, d(CGPXGCCGCCGA) with its complementary strand d(TCGGCGPXGCCG) (where X = O or S, i.e., PT-free dsDNA, [Sp, Sp]-PT dsDNA or [Rp, Rp]-PT dsDNA) located in gene of Streptomyces lividans. Their melting temperature (Tm) measurement indicates that [Rp, Rp]-PT dsDNA is most unstable. Their electron transfer potential detection presents an order of anti-oxidation properties: Sp-PT DNA > Rp-PT DNA > PT-free DNA. Their NMR structures demonstrate that PT modification doesn’t change their B-form conformation. The sulfur in [Rp, Rp]-PT dsDNA locates in the major groove, with steric effects on protons in the sugar close to modification sites, resulting in its unstability and facilitating its selectively interactions with ScoMcrA. We thought that PT modification was dialectical to the bacteria. It protects the hosting bacteria by working as antioxidant against H2O2 and acts as a marker, directing restriction enzyme observed in other hosts, like ScoMcrA, to correctly cleave the PT modified DNA, so that bacteria cannot spread and survive.
Analysis of the genetic association between IL27 variants and coronary artery disease in a Chinese Han population
Authors: Fan Qian , Nie Shaofang , Li Sihui , Liao Yuhua , Zhang Hongsong , Zha Lingfeng , Wang Fan , Tang Tingting , Xia Ni , Xu Chengqi , Wang Pengyun , Xie Tian , Xie Jiangjiao , Lu Qiulun , Li Qingxian , Qian Jin , Li Bin , Wu Gang , Wu Yanxia , Yang Yan , Wang Qing K. , Tu Xin , Cheng Xiang
Published: May 2016

Interleukin-27 (IL-27) is an important cytokine in inflammatory diseases, including coronary artery disease (CAD). To explore the precise role of IL-27 in CAD, we investigated the genetic association between IL27 and CAD in the GeneID Chinese Han population. A two-stage case control association analysis was performed for 3075 CAD cases and 2802 controls. Logistic regression analysis was used to adjust the traditional risk factors for CAD. Results showed that a promoter variant, rs153109, tended to be marginally associated with CAD in the discovery population (Padj = 0.028, OR = 1.27, 95%CI: 1.03–1.58). However, this association was not replicated in the validation stage (Padj = 0.559, OR = 1.04, 95%CI: 0.90–1.21). In addition, when we classified the combined population into two subgroups according to the age at disease onset or disease state, we again obtained no significant associations. Finally, we estimated the severity of coronary stenosis using the Gensini Scoring system and determined that the rs153109 genotypes were still not associated with the Gensini scores of the CAD patients. In conclusion, our study failed to find an association between common variants in the functional region of IL27 and CAD in a Chinese Han population, which indicated that IL-27 might only be an inflammatory marker during the development of CAD.
Anomalous enhancement of the sheet carrier density beyond the classic limit on a SrTiO3 surface
Authors: Kumar Neeraj , Kitoh Ai , Inoue Isao H.
Published: May 2016

Electrostatic carrier accumulation on an insulating (100) surface of SrTiO3 by fabricating a field effect transistor with Parylene-C (6 nm)/HfO2 (20 nm) bilayer gate insulator has revealed a mystifying phenomenon: sheet carrier density "Equation missing" is about 10 times as large as "Equation missing" ("Equation missing" is the sheet capacitance of the gate insulator, VG is the gate voltage and e is the elementary charge). The channel is so clean to exhibit small subthreshod swing of 170 mV/decade and large mobility of 11 cm2/Vs for "Equation missing" of 1 × 1014 cm−2 at room temperature. Since "Equation missing" does not depend on either VG nor time duration, "Equation missing" beyond "Equation missing" is solely ascribed to negative charge compressibility of the carriers, which was in general considered as due to exchange interactions among electrons in the small "Equation missing" limit. However, the observed "Equation missing" is too large to be naively understood by the framework. Alternative ideas are proposed in this work.
Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice
Authors: Cooley Lauren Folgosa , El Shikh Mohey Eldin , Li Wei , Keim Rebecca C. , Zhang Zhengang , Strauss Jerome F. , Zhang Zhibing , Conrad Daniel H.
Published: May 2016

Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the “9 + 2” axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses. Using bone marrow reconstitution studies of adult WT mice, we demonstrate that SPAG6 is expressed in primary and secondary lymphoid tissues, is associated with the centrosome in lymphocytes, and its deficiency results in synapse disruption due to loss of centrosome polarization and actin clearance at the synaptic cleft. Improper synapse formation in Spag6KO mice was associated with defective CTL functions and impaired humoral immunity as indicated by reduced germinal centers reactions, follicular CD4 T cells, and production of class-switched antibody, together with expansion of B1 B cells. This novel report demonstrates the requirement of SPAG6 for optimal synapse formation and function, its direct role in immune cell function, and provides a novel mechanism for infertility disorders related to SPAG6.
Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations
Authors: Prieto Gorka , Fullaondo Asier , Rodríguez Jose A.
Published: May 2016

Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC) and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21 and leads to the aberrant accumulation of this protein in the nucleus.
Flame-pyrolysis-prepared catalysts for the steam reforming of ethanol
Authors: Compagnoni Matteo , Lasso F. Josè , Di Michele Alessandro , Rossetti Ilenia
Published: May 2016

New catalysts were prepared by flame pyrolysis for ethanol steam reforming and were proven to be very active and stable.
Cationic polymers for DNA origami coating – examining their binding efficiency and tuning the enzymatic reaction rates
Authors: Kiviaho Jenny K. , Linko Veikko , Ora Ari , Tiainen Tony , Järvihaavisto Erika , Mikkilä Joona , Tenhu Heikki , Nonappa Nonappa , Kostiainen Mauri A.
Published: May 2016

Cationic polymers and DNA origami form electrostatic complexes for biotechnological applications.
Toward food analytics: fast estimation of lycopene and β-carotene content in tomatoes based on surface enhanced Raman spectroscopy (SERS)
Authors: Radu Andreea Ioana , Ryabchykov Oleg , Bocklitz Thomas Wilhelm , Huebner Uwe , Weber Karina , Cialla-May Dana , Popp Jürgen
Published: May 2016

The application of SERS toward the differentiation of two carotenoid molecules (namely, lycopene and β-carotene) in tomato samples is introduced.
Dual-emitting quantum dot/carbon nanodot-based nanoprobe for selective and sensitive detection of Fe3+ in cells
Authors: Wang Chuanxi , Huang Yijun , Jiang Kaili , Humphrey Mark G. , Zhang Chi
Published: May 2016

A novel dual-emitting fluorescence probe is developed for rapid and ultrasensitive detection of Fe3+.
Development of a rechargeable optical hydrogen peroxide sensor – sensor design and biological application
Authors: Koren Klaus , Jensen Peter Ø. , Kühl Michael
Published: May 2016

Measure and recharge!A reversible sensor concept enables repetitive and quantitative measurement of H2O2with high spatial and temporal resolution in environmental and biomedical samples.
Gold-catalyzed [4+3] and [4+4]-annulation reactions of t-butyl propiolate derivatives with epoxides and oxetanes for the construction of 1,4-dioxepane and 1,5-dioxocane cores
Authors: Sahani Rajkumar Lalji , Liu Rai-Shung
Published: May 2016

Gold-catalyzed [4+n]-annulations (n = 3, 4) of tert-butyl propiolate derivatives with epoxides or oxetanes proceed smoothly to yield seven- or eight-membered oxacyclic products efficiently.
13-Helix folding of a β/γ-peptide manifold designed from a “minimal-constraint” blueprint
Authors: Grison Claire M. , Robin Sylvie , Aitken David J.
Published: May 2016

A bottom-up design rationale was used to select an alternating β/γ-peptide motif which folds into a well-defined 13-helix in solution.
UV laser photoactivation of hexachloroplatinate bound to individual nucleobases in vacuo as molecular level probes of a model photopharmaceutical
Authors: Matthews Edward , Sen Ananya , Yoshikawa Naruo , Bergström Ed , Dessent Caroline E. H.
Published: May 2016

UV excitation of mass-selected hexachloroplatinate–nucleobase clusters provides detailed insight into the photophysics and photochemistry of a model DNA photopharmaceutical.
Synthetic advancements and catalytic applications of nickel nitride
Authors: Gage S. H. , Trewyn B. G. , Ciobanu C. V. , Pylypenko S. , Richards R. M.
Published: May 2016

This minireview discusses controlled chemical synthetic advancements of nickel nitride and its composites, their fundamental properties, and energy-related applications.
Lead ion induced chemodosimeter approach of a tripodal hydroxyl-quinoline based phospho-ester through P–O bond cleavage
Authors: Sain Dibyendu , Kumari Chanda , Kumar Ashish , Nayek Hari Pada , Dey Swapan
Published: May 2016

Pb2+ induced phosphoester hydrolysis followed by the formation of a penta coordinated chelate complex of lead.
Intestinal immunomodulating activity and structural characterization of a new polysaccharide from stems of Dendrobium officinale
Authors: Xie Song-Zi , Liu Bing , Zhang Dan-Dan , Zha Xue-Qiang , Pan Li-Hua , Luo Jian-Ping
Published: May 2016

A newly branchedDendrobium officinalepolysaccharide (DOP-W3-b) with a high intestinal immunomodulating activity and a relatively low molecular weight was obtained through a bioactivity-guided sequential isolation procedure.
High-throughput electrical measurement and microfluidic sorting of semiconductor nanowires
Authors: Akin Cevat , Feldman Leonard C. , Durand Corentin , Hus Saban M. , Li An-Ping , Hui Ho Yee , Filler Michael A. , Yi Jingang , Shan Jerry W.
Published: May 2016

Existing nanowire electrical characterization tools not only are expensive and require sophisticated facilities, but are far too slow to enable statistical characterization of highly variable samples.
Confinement and viscosity ratio effect on droplet break-up in a concentrated emulsion flowing through a narrow constriction
Authors: Gai Ya , Khor Jian Wei , Tang Sindy K. Y.
Published: May 2016

This paper describes the dimensionless groups that determine the break-up probability of droplets in a concentrated emulsion during its flow in a tapered microchannel consisting of a narrow constriction.
Protein labelling
Authors: Jones Lyn H. , Weerapana Eranthie
Published: May 2016

Professor Eranthie Weerapana and Professor Lyn Jones introduce this Protein Labelling themed issue.
The Atomic scale structure of liquid metal–electrolyte interfaces
Authors: Murphy B. M. , Festersen S. , Magnussen O. M.
Published: May 2016

Electrochemical interfaces between immiscible liquids have lately received renewed interest, both for gaining fundamental insight as well as for applications in nanomaterial synthesis.
Highly selective aerobic oxidation of alkyl arenes and alcohols: cobalt supported on natural hydroxyapatite nanocrystals
Authors: Shaabani Ahmad , Shaabani Shabnam , Afaridoun Hadi
Published: May 2016

Cobalt was successfully immobilized on natural hydroxyapatite nanocrystals which was obtained from cow bones (Co–NHAp). NHAp as the support enhanced both catalytic activity and selectivity in aerobic oxidation of alkyl arenes and alcohols.
p-TsOH-promoted synthesis of (E)-6-phenyl-7-styryl-5,6-dihydrodibenzo[b,h][1,6]naphthyridines via cascade intramolecular aza-Michael addition/Friedlander condensation of 2′-aminochalcones in a SDS/H2O system
Authors: Ravi Makthala , Chauhan Parul , Singh Shikha , Kant Ruchir , Yadav Prem. P.
Published: May 2016

p-TsOH-promoted one-pot cascade synthesis of novel (E)-6-phenyl-7-styryl-5,6-dihydrodibenzo[b,h][1,6]naphthyridines via homodimerization of 2′-aminochalcones has been developed in a SDS/H2O system.
Synthesis of a highly efficient phosphorus-containing flame retardant utilizing plant-derived diphenolic acids and its application in polylactic acid
Authors: Jing Jian , Zhang Yan , Tang Xinlei , Fang Zhengping
Published: May 2016

A highly efficient phosphorous-containing flame retardant for PLA is synthesized from plant-derived diphenolic acids.