bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin synergizes the chemotherapeutic effect of 5‐fluorouracil in colon cancer by suppressing PI3K/AKT and NF‐κB/iNOS signaling pathways
Authors: Gao Yue , Xiao Xiangsheng , Zhang Changlin , Yu Wendan , Guo Wei , Zhang Zhifeng , Li Zhenglin , Feng Xu , Hao Jiaojiao , Zhang Kefang , Xiao Bingyi , Chen Miao , Huang Wenlin , Xiong Shunbin , Wu Xiaojun , Deng Wuguo
Published: November 2016

5‐Fluorouracil (5‐FU) is one of the most commonly used chemotherapeutic agents in colon cancer treatment, but has a narrow therapeutic index limited by its toxicity. Melatonin exerts antitumor activity in various cancers, but it has never been combined with 5‐FU as an anticolon cancer treatment to improve the chemotherapeutic effect of 5‐FU. In this study, we assessed such combinational use in colon cancer and investigated whether melatonin could synergize the antitumor effect of 5‐FU. We found that melatonin significantly enhanced the 5‐FU‐mediated inhibition of cell proliferation, colony formation, cell migration and invasion in colon cancer cells. We also found that melatonin synergized with 5‐FU to promote the activation of the caspase/PARP‐dependent apoptosis pathway and induce cell cycle arrest. Further mechanism study demonstrated that melatonin synergized the antitumor effect of 5‐FU by targeting the PI3K/AKT and NF‐κB/inducible nitric oxide synthase (iNOS) signaling. Melatonin in combination with 5‐FU markedly suppressed the phosphorylation of PI3K, AKT, IKKα, IκBα, and p65 proteins, promoted the translocation of NF‐κB p50/p65 from the nuclei to cytoplasm, abrogated their binding to the iNOS promoter, and thereby enhanced the inhibition of iNOS signaling. In addition, pretreatment with a PI3K‐ or iNOS‐specific inhibitor synergized the antitumor effects of 5‐FU and melatonin. Finally, we verified in a xenograft mouse model that melatonin and 5‐FU exerted synergistic antitumor effect by inhibiting the AKT and iNOS signaling pathways. Collectively, our study demonstrated that melatonin synergized the chemotherapeutic effect of 5‐FU in colon cancer through simultaneous suppression of multiple signaling pathways.
High fodder value and feeding likelihood favour endozoochorous plant dispersal
Authors: Gilhaus Kristin , Freitag Martin , Kunze Svenja , Hölzel Norbert
Published: November 2016

Questions

In pasture‐dominated landscapes, endozoochory by large herbivores is an important vector of plant dispersal. Conditions influencing the potential for endozoochorous dispersal of plant species by grazers are, however, still poorly known. Here, we assess the impact of feeding habits and functional traits on the likelihood of endozoochorous dispersal by cattle (ruminants) and horses (non‐ruminants).

Location

Pasture of 27 ha in NW Germany, year‐round grazed by free‐ranging cattle and horses.

Methods

Vegetation relevés were established in 45 plots, from which dung samples of cattle and horses were collected. The number and composition of seedlings emerging from dung samples were compared with the vegetation of the study site in terms of plant functional trait composition. For the first time, feeding habits were included in the analysis. GLMs were used to identify traits that increased the potential for endozoochorous dispersal.

Results

A total of 65 species germinated from the dung samples. These species had higher average fodder and nutrient indicator values than the species composition of the vegetation. In particular, species found in horse dung were more tolerant of grazing and had more elongated seeds. The likelihood of endozoochorous dispersal was higher for common than for rare species and was influenced by feeding habits.

Conclusions

The likelihood of plant species being dispersed endozoochorously can be linked to different functional traits and is dependent on the type of grazer and the population size of target species in the vegetation. Differences between cattle and horses in seed dispersal may result from species‐specific grazing habits and different digestion modes.
Hereditary haemorrhagic telangiectasia: to transplant or not to transplant – is there a right time for liver transplantation?
Authors: Muller Yannick D. , Oppliger Roland , Breguet Romain , Meyer Philippe , Rubbia‐Brandt Laura , Petignat Pierre‐Auguste , Harr Thomas , Dayer Eric , Seebach Jörg D.
Published: November 2016

Background & Aims

Hereditary haemorrhagic telangiectasia is characterized by arterio‐venous malformations (AVM). It frequently involves the liver without clinical symptoms, but may lead to biliary ischaemia, portal hypertension, or fatal high‐output heart failure. The indication of liver transplantation is controversial.

Methods

Herein, we report the case of a 65‐year‐old female patient with a ‘double Osler syndrome’ consisting of hereditary haemorrhagic telangiectasia (HHT) and type I hereditary angioedema diagnosed at the age of 25 and 22 years respectively.

Results

Hereditary angioedema was treated with danazol for several decades until multiple hypoechogenic liver masses were detected. Albeit danazol treatment was replaced by C1 esterase inhibitor infusions, hepatocellular carcinoma was diagnosed at the age of 64 and the patient was listed for liver transplantation. HHT was marked by recurrent epistaxis until the age of 63 when severe intestinal bleeding occurred. At the age of 65, severe dyspnoea (NYHA class IV) developed and rapidly progressive high‐output cardiac failure was diagnosed. Despite argon plasma coagulation to control bleeding from intestinal angiodysplasia, and treatment with bevacizumab to inhibit angiogenesis, the patient died from severe gastrointestinal bleeding associated with cardiogenic shock at the age of 66 before being transplanted.

Conclusion

The indication to list this patient for liver transplantation was debated several times before the diagnosis of hepatocellular carcinoma because of good general condition and low MELD score. Precise guidelines for screening and management of patients with hepatic HHT need to be better defined.
Hereditary hemorrhagic telangiectasia: to transplant or not to transplant?
Authors: Dupuis‐Girod Sophie , Buscarini Elisabetta
Published: November 2016

This report comments the case reported by Muller et al. which describes a combination of at least two different indications for orthotopic liver transplant (OLT) in a same patient: hepatocarcinoma and HHT complicated with severe liver involvement and high output cardiac failure. This case report highlighted that the clear time for OLT in HHT can be difficult to determine. In HHT, if intensive medical approach is not efficient, OLT, has to be considered. In the case of Muller et al., the patient was correctly listed for OLT for a single hepatocellular carcinoma, however, he did not receive a sufficient priority so as to avoid worsening of liver vascular malformations complications. Bevacizumab may be a therapeutic option in the treatment of complicated liver VMs in HHT, However, the recurrence of symptoms after withdrawal of the drug make it unsuitable as a replacement for OLT in the cure of complicated liver VMs in HHT. In the case reported by Muller et al. the right “OLT window” after bevacizumab was lost.

The right time for OLT in severe complicated liver VMs in HHT does exist but, as this case illustrates, it can be very difficult to determine. As OLT is a radical cure for liver VMs, with excellent outcomes, it should be the therapeutic choice in patients under the age of 65 years. Bevacizumab may be an interesting option, either for patients over the age of 65 years, or those who are poor candidates for surgery; if these latter respond to bevacizumab they should be re‐ evaluated for OLT (with a “fast‐ track”) as the prognosis of severe complicated liver VMs is very poor.
Prognostic biomarkers and surrogate end points in PSC
Authors: Vesterhus Mette , Melum Espen
Published: November 2016

See Article on Page 1867
Hereditary haemorrhagic telangiectasia: to transplant or not to transplant?
Authors: Sabbà Carlo
Published: November 2016

The Association of hereditary hemorrhagic telangiectasia (HHT) and type I hereditary angioedema is a very rare condition in medicine. The case reported by Muller et al., describes the coexistence of the two diseases and emphasizes the need for listing HHT patients for liver transplantation in case indications occurs, such as the presence of HCC, abnormally increased cardiac output, and gastrointestinal bleeding as reported for this case. The case described by Mueller et al. is anecdotal for the usefulness of liver transplantation in HHT patients and shows that liver transplantation may be the best supportive care and, sometimes, the unique and final therapeutic option for these patients.
Management of hepatitis B‐related cirrhosis in the era of effective antiviral therapy
Authors: Wong Vincent W. S.
Published: November 2016

See Article on Page 1755
Survival at 2 years among liver cirrhotic patients is influenced by left atrial volume and left ventricular mass
Authors: Merli Manuela , Torromeo Concetta , Giusto Michela , Iacovone Gianna , Riggio Oliviero , Puddu Paolo E.
Published: November 2016

Background & Aims

Cirrhotic cardiomyopathy (CC) may interact with the clinical course of cirrhosis and can be implicated in the development of several complications in advanced liver disease. The best and easiest parameters which should define a condition of reduced cardiac reserve in cirrhosis are still controversial. This study was aimed at selecting the cardiac parameters, derived by Doppler echocardiography, predictive of survival during follow‐up.

Methods

This study included cirrhotic patients without cardiovascular or pulmonary diseases. Patients were studied in stable conditions. Doppler echocardiography was used to select parameters associated with survival. Among the others, left atrial volume (LAVi) and left ventricular mass indexed to body surface area (LVMi) were evaluated. A comparison was performed with the parameters presently applied for the definition of CC according to the Montreal criteria.

Results

Ninety cirrhotic patients have been included (males 66%, alcohol origin 31%, post‐viral 54%, Child‐Pugh A 53%, B 29% and C 18%). Patients were followed up for at least 24 months. Twenty‐six patients had a diagnosis of CC according to the Montreal criteria. During follow‐up, 24 patients died. Overall mortality was 26.7%. Patients presenting higher LAVi and lower LVMi were those at higher risk to die (P=.04 and P=.007 respectively). No difference in survival was seen in patients with a diagnosis of CC.

Conclusions

An increased LAVi and a decreased LVMi were able to differentiate among patients with a lower survival at 2 years. These parameters need to be considered for prognostic evaluation in cirrhotics.
Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre‐ to post‐liver transplant: a real‐life strategy
Authors: Donato Maria Francesca , Morelli Cristina , Romagnoli Renato , Invernizzi Federica , Mazzarelli Chiara , Iemmolo Rosa Maria , Montalbano Marzia , Lenci Ilaria , Bhoori Sherrie , Pieri Giulia , Berardi Sonia , Caraceni Paolo , Martini Silvia ,   ITACOPS‐SOF Bridging Study Group
Published: November 2016

Background & Aims

Hepatitis C virus (HCV) re‐infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF‐regimen from pre‐ to post‐transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV‐RNA undetectability at the time of transplant.

Methods

From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One hundred patients were transplanted and 31 patients (31%) treated with SOF/R bridging therapy were studied.

Results

Liver transplant indication in bridge subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV‐genotype was 1/4 in 18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a median of 35 days before LT. At transplant time, 19 patients were still HCV‐RNA positive (median HCV‐RNA 58 IU/mL). One recipient had a virological breakthrough at week 4 post‐transplant; one died, on treatment, 1‐month post‐transplant for sepsis and 29/31 achieved a 12‐week sustained virological response (94%). Acute cellular rejection occurred in three recipients. On September 2016, 30 recipients (97%) were alive with a median follow‐up of 18 months (range 13‐25).

Conclusions

In patients with suboptimal virological response at LT, a bridging SOF/R regimen helps avoiding post‐transplant graft reinfection.
Introgression of mtDNA in Urosaurus lizards: historical and ecological processes
Authors: Haenel Gregory J.
Published: November 2016

Introgression of mtDNA appears common in animals, but the implications of acquiring a novel mitochondrial genome are not well known. This study investigates mito‐genome introgression between the lizard species Urosaurus graciosus, a thermal specialist, and U. ornatus, a species that occupies a wider range of thermal environments. As ectotherms, their metabolic rate is strongly influenced by the thermal environment; with mitochondria being linked to metabolic rates, overall energy budgets could be impacted by introgression. I use mitochondrial gene trees, inferred from Bayesian analyses of Cyt‐B and ND1 gene sequences, along with morphology and microsatellites from nineteen populations of these two species to address if the direction and location of mito‐nuclear discordance match predictions of introgression resulting from past population expansions. MtDNA is expected to move from resident species into expanding or invading species. Second, does having a heterospecific form of mitochondria impact body size, a trait strongly associated with fitness? Multiple independent introgression events of historic origin were detected. All introgression was unidirectional with U. ornatus‐type mtDNA found in U. graciosus parental type individuals. This result was consistent with population expansions detected in U. graciosus but not U. ornatus. Females with heterospecific mtDNA were significantly smaller than homospecific forms, and heterospecific males had a different relationship of body mass to body length than those with homospecific mtDNA. These changes indicate a potential selective disadvantage for individuals with heterospecific mitochondria and are consistent with the theoretical expectation that deleterious alleles are more likely to persist in expanding populations.
Recombination rate variation in mice from an isolated island
Authors: Wang Richard J. , Gray Melissa M. , Parmenter Michelle D. , Broman Karl W. , Payseur Bret A.
Published: November 2016

Recombination rate is a heritable trait that varies among individuals. Despite the major impact of recombination rate on patterns of genetic diversity and the efficacy of selection, natural variation in this phenotype remains poorly characterized. We present a comparison of genetic maps, sampling 1212 meioses, from a unique population of wild house mice (Mus musculus domesticus) that recently colonized remote Gough Island. Crosses to a mainland reference strain (WSB/EiJ) reveal pervasive variation in recombination rate among Gough Island mice, including subchromosomal intervals spanning up to 28% of the genome. In spite of this high level of polymorphism, the genomewide recombination rate does not significantly vary. In general, we find that recombination rate varies more when measured in smaller genomic intervals. Using the current standard genetic map of the laboratory mouse to polarize intervals with divergent recombination rates, we infer that the majority of evolutionary change occurred in one of the two tested lines of Gough Island mice. Our results confirm that natural populations harbour a high level of recombination rate polymorphism and highlight the disparities in recombination rate evolution across genomic scales.
Genomic islands of divergence linked to ecotypic variation in sockeye salmon
Authors: Larson Wesley A. , Limborg Morten T. , McKinney Garrett J. , Schindler Daniel E. , Seeb James E. , Seeb Lisa W.
Published: November 2016

Regions of the genome displaying elevated differentiation (genomic islands of divergence) are thought to play an important role in local adaptation, especially in populations experiencing high gene flow. However, the characteristics of these islands as well as the functional significance of genes located within them remain largely unknown. Here, we used data from thousands of SNPs aligned to a linkage map to investigate genomic islands of divergence in three ecotypes of sockeye salmon (Oncorhynchus nerka) from a single drainage in southwestern Alaska. We found ten islands displaying high differentiation among ecotypes. Conversely, neutral structure observed throughout the rest of the genome was low and not partitioned by ecotype. One island on linkage group So13 was particularly large and contained six SNPs with FST > 0.14 (average FST of neutral SNPs = 0.01). Functional annotation revealed that the peak of this island contained a nonsynonymous mutation in a gene involved in growth in other species (TULP4). The islands that we discovered were relatively small (80–402 Kb), loci found in islands did not show reduced levels of diversity, and loci in islands displayed slightly elevated linkage disequilibrium. These attributes suggest that the islands discovered here were likely generated by divergence hitchhiking; however, we cannot rule out the possibility that other mechanisms may have produced them. Our results suggest that islands of divergence serve an important role in local adaptation with gene flow and represent a significant advance towards understanding the genetic basis of ecotypic differentiation.
Stimulation effects of ciprofloxacin and sulphamethoxazole in Microcystis aeruginosa and isobaric tag for relative and absolute quantitation‐based screening of antibiotic targets
Authors: Liu Ying , Chen Shi , Zhang Jian , Li Xuewen , Gao Baoyu
Published: November 2016

Antibiotics are normally regarded as safe to aquatic ecosystems when their contamination concentrations are lower than the toxic threshold. This study observed the hazard of ciprofloxacin, sulphamethoxazole and their binary mixture to the aquatic environment at environmentally relevant concentrations lower than the toxic threshold, due to the stimulation on the bloom of Microcystis aeruginosa. The enhanced growth of M. aeruginosa, coupled with elevated photosynthesis activity, was exerted by 50–200 ng/L of ciprofloxacin, 100–200 ng/L of sulphamethoxazole and 20–100 ng/L of the binary antibiotic mixture. Stimulated production and release of microcystins were observed at even lower concentrations. The upregulation of transcription‐related proteins, cell division‐related proteins, a gas vesicle protein, a global nitrogen regulator (ntcA), two microcystin synthetases (mcyC and mcyH) and ATP‐binding cassette transporters provided direct proteomic evidence for the regulation of target antibiotics on M. aeruginosa bloom. Cytochrome P450 was an essential component involved in stress responses and antibiotic biodegradation. Proteomic responses to antibiotic exposure presented a shift in the energy metabolism of M. aeruginosa towards the excitation of photosynthesis, an increase of carbohydrate biosynthesis and the inhibition of carbohydrate catabolism. Superoxide dismutase, enolase and D1 protein were candidate target proteins of different antibiotics in M. aeruginosa. The antibiotic mixture showed a greater hazard than single antibiotics, and a safe threshold of 5 ng/L was suggested for each target antibiotic under the coexistence condition.
Spatio‐temporal variation in parasite communities maintains diversity at the major histocompatibility complex class IIβ in the endangered Rio Grande silvery minnow
Authors: Osborne Megan J. , Pilger Tyler J. , Lusk Joel D. , Turner Thomas F.
Published: November 2016

Climate change will strongly impact aquatic ecosystems particularly in arid and semi‐arid regions. Fish–parasite interactions will also be affected by predicted altered flow and temperature regimes, and other environmental stressors. Hence, identifying environmental and genetic factors associated with maintaining diversity at immune genes is critical for understanding species’ adaptive capacity. Here, we combine genetic (MHC class IIβ and microsatellites), parasitological and ecological data to explore the relationship between these factors in the remnant wild Rio Grande silvery minnow (Hybognathus amarus) population, an endangered species found in the southwestern United States. Infections with multiple parasites on the gills were observed and there was spatio‐temporal variation in parasite communities and patterns of infection among individuals. Despite its highly endangered status and chronically low genetic effective size, Rio Grande silvery minnow had high allelic diversity at MHC class IIβ with more alleles recognized at the presumptive DAB1 locus compared to the DAB3 locus. We identified significant associations between specific parasites and MHC alleles against a backdrop of generalist parasite prevalence. We also found that individuals with higher individual neutral heterozygosity and higher amino acid divergence between MHC alleles had lower parasite abundance and diversity. Taken together, these results suggest a role for fluctuating selection imposed by spatio‐temporal variation in pathogen communities and divergent allele advantage in maintenance of high MHC polymorphism. Understanding the complex interaction of habitat, pathogens and immunity in protected species will require integrated experimental, genetic and field studies.
Molecular and microstructural inventory of an isolated fossil bird feather from the Eocene Fur Formation of Denmark
Authors: Gren Johan A. , Sjövall Peter , Eriksson Mats E. , Sylvestersen Rene L. , Marone Federica , Sigfridsson Clauss Kajsa G. V. , Taylor Gavin J. , Carlson Stefan , Uvdal Per , Lindgren Johan
Published: November 2016

An isolated, yet virtually intact contour feather (FUM‐1980) from the lower Eocene Fur Formation of Denmark was analysed using multiple imaging and molecular techniques, including field emission gun scanning electron microscopy (FEG‐SEM), X‐ray absorption spectroscopy and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Additionally, synchrotron radiation X‐ray tomographic microscopy (SRXTM) was employed in order to produce a digital reconstruction of the fossil. Under FEG‐SEM, the proximal, plumulaceous part of the feather revealed masses of ovoid microstructures, about 1.7 μm long and 0.5 μm wide. Microbodies in the distal, pennaceous portion were substantially smaller (averaging 0.9 × 0.2 μm), highly elongate, and more densely packed. Generally, the microbodies in both the plumulaceous and pennaceous segments were aligned along the barbs and located within shallow depressions on the exposed surfaces. Biomarkers consistent with animal eumelanins were co‐localized with the microstructures, to suggest that they represent remnant eumelanosomes (i.e. eumelanin‐housing cellular organelles). Additionally, ToF‐SIMS analysis revealed the presence of sulfur‐containing organics – potentially indicative of pheomelanins – associated with eumelanin‐like compounds. However, since there was no correlation between melanosome morphology and sulfur content, we conclude these molecular structures derive from diagenetically incorporated sulfur rather than pheomelanin. Melanosomes corresponding roughly in both size and morphology with those in the proximal part of FUM‐1980 are known from contour feathers of extant parrots (Psittaciformes), an avian clade that has previously been reported from the Fur Formation.
Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference
Authors: Gan Emily Y. , Eleftheriadou Viktoria , Esmat Samia , Hamzavi Iltefat , Passeron Thierry , Böhm Markus , Anbar Tag , Goh Boon Kee , Lan Cheng‐Che E. , Lui Harvey , Ramam M. , Raboobee Noufal , Katayama Ichiro , Suzuki Tamio , Parsad Davinder , Seth Vaneeta , Lim Henry W. , van Geel Nanja , Mulekar Sanjeev , Harris John , Wittal Richard , Benzekri Laila , Gauthier Yvon , Kumarasinghe Prasad , Thng Steven T. G. , Silva de Castro Caio Cesar , Abdallah Marwa , Vrijman Charlotte , Bekkenk Marcel , Seneschal Julien , Pandya Amit G. , Ezzedine Khaled , Picardo Mauro , Taïeb Alain ,   the VGICC
Published: November 2016

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e‐Delphi consensus, concluded that ‘repigmentation’ and ‘maintenance of gained repigmentation’ are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e‐surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e‐surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.
Biological hypotheses and biomarkers of bipolar disorder
Authors: Sigitova Ekaterina , Fišar Zdeněk , Hroudová Jana , Cikánková Tereza , Raboch Jiří
Published: November 2016

The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune‐inflammatory, neurotransmitter, neurotrophin, and calcium‐signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.
Mfd Protein and Transcription–Repair Coupling in Escherichia coli
Authors: Selby Christopher P.
Published: November 2016

In 1989, transcription–repair coupling (TRC) was first described in Escherichia coli, as the transcription‐dependent, preferential nucleotide excision repair (NER) of UV photoproducts located in the template DNA strand. This finding led to pioneering biochemical studies of TRC in the laboratory of Professor Aziz Sancar, where, at the time, major contributions were being made toward understanding the roles of the UvrA, UvrB and UvrC proteins in NER. When the repair studies were extended to TRC, template but not coding strand lesions were found to block RNA polymerase (RNAP) in vitro, and unexpectedly, the blocked RNAP inhibited NER. A transcription–repair coupling factor, also called Mfd protein, was found to remove the blocked RNAP, deliver the repair enzyme to the lesion and thereby mediate more rapid repair of the transcription‐blocking lesion compared with lesions elsewhere. Structural and functional analyses of Mfd protein revealed helicase motifs responsible for ATP hydrolysis and DNA binding, and regions that interact with RNAP and UvrA. These and additional studies provided a basis upon which other investigators, in following decades, have characterized fascinating and unexpected structural and mechanistic features of Mfd, revealed the possible existence of additional pathways of TRC and discovered additional roles of Mfd in the cell.
Phylogenetic and Functional Classification of the Photolyase/Cryptochrome Family
Authors: Ozturk Nuri
Published: November 2016

The photolyase/cryptochrome (PHR/CRY) family is a large group of proteins with similar structure but very diverge functions such as DNA repair, circadian clock resetting and regulation of transcription. As a result of advances in the biochemistry of the CRY/PHR family and identification of new members, several adjustments have been made to the classification of this protein family. For example, a new class of PHRs, Class III, has been proposed. Furthermore, CRYs have been suggested to function as photosensory proteins in the primordial eye of sponge larvae. Additionally, a magnetosensory function has been attributed to certain CRYs. Recent advances in the field enabled us to propose a comprehensive classification scheme and nomenclatural system for this family. This review focuses on the computational and biochemical classifications of the PHR/CRY family. Several examples show that computational analysis can give a hinge about the function of newly discovered members before performing any biochemical study.
Evaluation of the efficacy of photodynamic therapy for the treatment of actinic cheilitis
Authors: Chaves Yuri N. , Torezan Luis Antonio , Lourenço Silvia Vanessa , Neto Cyro Festa
Published: November 2016

Introduction

Actinic cheilitis (AC) is a lip intraepithelial neoplasia, whose cells present alterations similar to those presented by invasive squamous cell carcinomas (SCCs).

Objective

To conduct clinical and laboratory evaluation by histopathology and immunohistochemistry of the efficacy of actinic cheilitis treatment using photodynamic therapy (PDT) with methyl aminolevulinate (MAL) and noncoherent red light.

Materials and methods

Patients with actinic cheilitis detected by histopathological examination were submitted to two sessions of photodynamic therapy with a two‐week interval between them. They were examined immediately after the sessions, four, six, and twelve weeks after beginning treatment when a new biopsy was carried out. Clinical histopathological and immunohistochemical parameters were evaluated before and after treatment.

Results

Of the 23 patients who underwent biopsy, 16 completed two photodynamic therapy sessions and the material of one patient was insufficient for immunohistochemistry. Complete clinical response was achieved in 62.5% (10 of 16 patients) and 37.5% still remained with clinical evidence of AC. In spite of this, no case of cure by histopathological analysis was found. There was no significant statistical change among the values of Ki‐67, survivin, and p53 observed before and after treatment.

Conclusion

Photodynamic therapy, as carried out in this trial, was not an efficacious therapeutic option for treating patients with actinic cheilitis included in this sample.
Parameter Stability and Semiparametric Inference in Time Varying Auto-Regressive Conditional Heteroscedasticity Models
Authors: Truquet Lionel
Published: November 2016

We develop a complete methodology for detecting time varying or non-time-varying parameters in auto-regressive conditional heteroscedasticity (ARCH) processes. For this, we estimate and test various semiparametric versions of time varying ARCH models which include two well-known non-stationary ARCH-type models introduced in the econometrics literature. Using kernel estimation, we show that non-time-varying parameters can be estimated at the usual parametric rate of convergence and, for Gaussian noise, we construct estimates that are asymptotically efficient in a semiparametric sense. Then we introduce two statistical tests which can be used for detecting non-time-varying parameters or for testing the second-order dynamics. An information criterion for selecting the number of lags is also provided. We illustrate our methodology with several real data sets.
Flooding scenarios due to land subsidence and sea‐level rise: a case study for Lipari Island (Italy)
Authors: Anzidei Marco , Bosman Alessandro , Carluccio Roberto , Casalbore Daniele , D'Ajello Caracciolo Francesca , Esposito Alessandra , Nicolosi Iacopo , Pietrantonio Grazia , Vecchio Antonio , Carmisciano Cosmo , Chiappini Massimo , Chiocci Francesco Latino , Muccini Filippo , Sepe Vincenzo
Published: November 2016

Archaeological and instrumental data indicate that the southern sector of the volcanic island of Lipari has been subsiding for the last 2100 years due to isostatic and tectonic factors, at variable rates of up to ~11 mm a−1. Based on this data, a detailed marine flooding scenario for 2100 AD is provided for the bay of Marina Lunga in the eastern part of the island from (1) an ultra‐high‐resolution Digital Terrain and Marine Model (DTMM) generated from multibeam bathymetry (MB) and Unmanned Aerial Vehicles (UAV), (2) the rate of land subsidence from Global Positioning System (GPS) data and (3) the regional sea‐level projections of the International Panel on Climate Change (IPCC). When land subsidence is considered, the upper bound of sea‐level rise is estimated at 1.36 m and 1.60 m for RCP4.5 and RCP8.5 climate change scenarios, respectively. Here, we show the expected impact of marine flooding at Lipari for the next 85 years and discuss the hazard implications for the population living along the shore.
The regulation of carotenoid formation in tomato fruit
Authors: Enfissi Eugenia M.A. , Nogueira Marilise , Bramley Peter M. , Fraser Paul D.
Published: November 2016

Carotenoid biosynthesis in plants includes a complex series of desaturation/isomerisation reactions, catalyzed by four independent enzymes. In bacteria and fungi one desaturase/isomerase enzyme completes the same series of reactions. In the present study, a bacterial desaturase (crtI) from Pantoea ananatis has been overexpressed in the tangerine mutant of tomato (Solanum lycopersicon) which accumulates cis‐carotene isomers in the fruit due to a defective isomerase (CRTISO) and the old gold crimson (ogc) tomato mutant, which is defective in the fruit‐enhanced lycopene β‐cyclase (CYCB). Comprehensive molecular and biochemical characterization of the resulting lines expressing crtI has revealed negative feedback mechanisms, acting predominantly at the level of phytoene synthase‐1 (PSY1), and feed‐forward mechanisms inducing cyclisation. In both cases, altered transcription appears to be the progenitor, with subsequent post‐transcriptional modulation highlighting the complexity of the processes involved in modulating carotenoid homeostasis in plant tissues.
Whistling Tea Kettles, Train Whistles, and Organ Pipes
Authors: Greenslade Thomas B.
Published: November 2016

The object on the right-hand side of Fig. 1 is the whistling mechanism of an old-fashioned tea kettle. This started me thinking about similar devices in which a thin blade of air strikes a sharp wedge and a resonator is used to pick out specific frequencies. This note tells how I went about using the frequency spectrum application on a smartphone to learn more about these systems. This would seem to be a good line of small-scale research that would appeal to the introductory physics student who is searching for a science fair project.
The Chappaquiddick Incident
Authors: Cross Rod
Published: November 2016

On July 19, 1969, Senator Edward Kennedy drove his vehicle off a low bridge on Chappaquiddick Island in Massachusetts. The vehicle sank in 2.1 m of water, coming to rest on its roof. According to Kennedy’s version of events, he managed to escape from the submerged vehicle without injury, but his female companion, Mary Jo Kopechne, drowned without any sign of injury. He did not report the accident to police until 10 hours later. Kennedy’s version of the events was widely disbelieved but was never seriously challenged by the local police or accident investigators or at the subsequent inquest. The accident effectively put an end to Kennedy’s bid for the presidency of the United States. At least a dozen books have been written on the subject, offering alternative explanations but the physics of the accident itself has never been properly investigated. In this paper experiments using a toy vehicle are described where the vehicle was projected into a container of water to investigate how the roof may have been damaged. The trajectory through the water was filmed and is explained in terms of elementary physics. Further investigation could be the subject of student projects and would provide an interesting introduction to forensic physics.
100 Years of Attempts to Transform Physics Education
Authors: Otero Valerie K. , Meltzer David E.
Published: November 2016

As far back as the late 1800s, U.S. physics teachers expressed many of the same ideas about physics education reform that are advocated today. However, several popular reform efforts eventually failed to have wide impact, despite strong and enthusiastic support within the physics education community. Broad-scale implementation of improved instructional models today may be just as elusive as it has been in the past, and for similar reasons. Although excellent instructional models exist and have been available for decades, effective and scalable plans for transforming practice on a national basis have yet to be developed and implemented. Present-day teachers, education researchers, and policy makers can find much to learn from past efforts, both in their successes and their failures. To this end, we present a brief outline of some key ideas in U.S. physics education during the past 130 years. We address three core questions that are prominent in the literature: (a) Why and how should physics be taught? (b) What physics should be taught? (c) To whom should physics be taught? Related issues include the role of the laboratory and attempts to make physics relevant to everyday life. We provide here only a brief summary of the issues and debates found in primary-source literature; an extensive collection of historical resources on physics education is available at https://sites.google.com/site/physicseducationhistory/home.
Reflections on a Disco Ball
Authors: Ribeiro Jair Lúcio Prados
Published: November 2016

A disco ball is a spherical object covered with small plane mirrors. When light reflects on these mirrors, it is scattered in many directions, producing a novel effect. The mirror globe is usually set to rotate, creating a profusion of moving spots (Fig. 1). In this article, we present a geometrical description of the movement of these spots and an experimental activity to test the model.
Seniors attending public high schools
Authors: White Susan C.
Published: November 2016

We have been looking at two different numbers that have been used to describe the availability of physics in U.S. high schools: 60% and 95%. Last month we noted that the U.S. Department of Education Office of Civil Rights (OCR) includes over 7000 more public schools in the denominator than AIP Statistics does. Almost 4000 of the additional schools are special education, alternative, or other schools that do have seniors enrolled. An additional ∼3350 are schools that have a grade 9, 10, 11, or 12, but no seniors enrolled. The 95% number reported by AIP Statistics is the proportion of seniors attending a school where physics is offered regularly. The italicized words explain the bulk of the difference between the 60% and 95%.
The Atomic Origin of the Reflection Law
Authors: Prytz Kjell
Published: November 2016

It will be demonstrated how the reflection law may be derived on an atomic basis using the plane wave approximation together with Huygens’ principle. The model utilized is based on the electric dipole character of matter originating from its molecular constituents. This approach is not new but has, since it was first introduced by Ewald and Oseen in 1915, been applied and analyzed many times before. Here we develop the Ewald-Oseen model of reflection adapted for high school and early undergraduate students with a basic knowledge of microscopic material structure.
Kinematics Card Sort Activity: Insight into Students’ Thinking
Authors: Berryhill Erin , Herrington Deborah , Oliver Keith
Published: November 2016

Kinematics is a topic students are unknowingly aware of well before entering the physics classroom. Students observe motion on a daily basis. They are constantly interpreting and making sense of their observations, unintentionally building their own understanding of kinematics before receiving any formal instruction. Unfortunately, when students take their prior conceptions to understand a new situation, they often do so in a way that inaccurately connects their learning. We were motivated to identify strategies to help our students make accurate connections to their prior knowledge and understand kinematics at a deeper level. To do this, we integrated a formative assessment card sort into a kinematic graphing unit within an introductory high school physics course. Throughout the activities, we required students to document and reflect upon their thinking. This allowed their learning to build upon their own previously held conceptual understanding, which provided an avenue for cognitive growth. By taking a more direct approach to eliciting student reasoning, we hoped to improve student learning and guide our assessment of their learning.
Getting Hooked on Physics!
Authors: McHugh M. , McCauley V.
Published: November 2016

A number of papers in this journal have dealt with the idea of using hooks in physics instruction. A hook, as the name suggests, engages students in learning by triggering their attention and interest. Hooks can be any type of pedagogical approach—a question, a demonstration, a puzzle or video. They are generally short and center on the most interesting aspects of a topic. Here we focus on using Conceptual Change (CC) teacher-led demonstrations as the pedagogical hook approach. Conceptual Change is an instructional method mentioned by a number of authors to stimulate interest among learners. This is where an educator presents an issue or topic that has associated misconceptions. As the teacher explains the truth behind the concept, cognitive conflict occurs and the students’ initial perceptions are challenged and ideas start to change. However, the instruction used in association with the demonstrations must provide intelligible, plausible, relevant explanations so that students are convinced by the new ideas. The gap between prior knowledge and new knowledge has the potential to provide a strong stimulus for augmenting interest, engagement, and attention among students. Thus, CC can act as a hook in itself.
At the Limit: Introducing Energy with Human Senses
Authors: Stinken Lisa , Heusler Stefan , Carmesin Hans-Otto
Published: November 2016

Energy belongs to the core ideas of the physics curriculum. But at the same time, energy is one of the most complex topics in science education since it occurs in multiple ways, such as motion, sound, light, and thermal energy. It can neither be destroyed nor created, but only converted. Due to the variety of relevant scales and abstractness of the term energy, the question arises how to introduce energy at the introductory physics level. The aim of this article is to demonstrate how the concept of energy can become meaningful in the context of the human senses. Three simple experiments to investigate the minimal amount of energy that is required to generate a sensory perception are presented. In this way students can learn that even different sensory perceptions can be compared by using energy as the unifying concept.
KDM5 lysine demethylases are involved in maintenance of 3′UTR length
Authors: Blair Lauren P. , Liu Zongzhi , Labitigan Ramon Lorenzo D. , Wu Lizhen , Zheng Dinghai , Xia Zheng , Pearson Erica L. , Nazeer Fathima I. , Cao Jian , Lang Sabine M. , Rines Rachel J. , Mackintosh Samuel G. , Moore Claire L. , Li Wei , Tian Bin , Tackett Alan J. , Yan Qin
Published: November 2016

New roles of an epigenetic regulator in RNA processing are discovered, which could be targeted for cancer treatment.
The thermodynamic scale of inorganic crystalline metastability
Authors: Sun Wenhao , Dacek Stephen T. , Ong Shyue Ping , Hautier Geoffroy , Jain Anubhav , Richards William D. , Gamst Anthony C. , Persson Kristin A. , Ceder Gerbrand
Published: November 2016

Data-mining the stability of 29,902 material phases reveals the thermodynamic landscape of inorganic crystalline metastability.
Discovery of true electrochemical reactions for ultrahigh catalyst mass activity in water splitting
Authors: Mo Jingke , Kang Zhenye , Retterer Scott T. , Cullen David A. , Toops Todd J. , Green Johney B. , Mench Matthew M. , Zhang Feng-Yuan
Published: November 2016

Increase 50-time catalyst mass activity from revealing true reactions in proton exchange membrane electrolysis.
Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration
Authors: Chen William C. W. , Wang Zhouguang , Missinato Maria Azzurra , Park Dae Woo , Long Daniel Ward , Liu Heng-Jui , Zeng Xuemei , Yates Nathan A. , Kim Kang , Wang Yadong
Published: November 2016

Mammalian heart regeneration after acute heart attacks can be induced by decellularized zebrafish cardiac extracellular matrix.
Single-cell analysis reveals a nestin
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tendon stem/progenitor cell population with strong tenogenic potentiality
Authors: Yin Zi , Hu Jia-jie , Yang Long , Zheng Ze-Feng , An Cheng-rui , Wu Bing-bing , Zhang Can , Shen Wei-Liang , Liu Huan-huan , Chen Jia-lin , Heng Boon Chin , Guo Guo-ji , Chen Xiao , Ouyang Hong-Wei
Published: November 2016

Nestin defines a novel tendon stem/progenitor cell subpopulation with high tenogenesis potential.
The activation loop of PIP5K functions as a membrane sensor essential for lipid substrate processing
Authors: Liu Aizhuo , Sui Dexin , Wu Dianqing , Hu Jian
Published: November 2016

A nuclear magnetic resonance study reveals the molecular basis of activation and regulation of the lipid kinase PIP5K by membrane lipids.
Adhesion mechanisms of curli subunit CsgA to abiotic surfaces
Authors: DeBenedictis Elizabeth P. , Liu Jenny , Keten Sinan
Published: November 2016

The curli fiber subunit, CsgA, adheres strongly to abiotic surfaces through side-chain interactions and also exhibits correlated motion.
Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase
Authors: Xia Jun , Chen Li-Tzu , Mei Qian , Ma Chien-Hui , Halliday Jennifer A. , Lin Hsin-Yu , Magnan David , Pribis John P. , Fitzgerald Devon M. , Hamilton Holly M. , Richters Megan , Nehring Ralf B. , Shen Xi , Li Lei , Bates David , Hastings P. J. , Herman Christophe , Jayaram Makkuni , Rosenberg Susan M.
Published: November 2016

Freeze-frame synthetic proteins trap DNA reaction intermediates in single live cells, revealing origins of genome instability.