bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of suboptimal neoadjuvant chemotherapy on peri‐operative outcomes and survival after robot‐assisted radical cystectomy: a multicentre multinational study
Authors: Hinata Nobuyuki , Hussein Ahmed Aly , George Saby , Trump Donald L. , Levine Ellis G. , Omar Kawa , Dasgupta Prokar , Khan Muhammad Shamim , Hosseini Abolfazl , Wiklund Peter , Guru Khurshid A.
Published: October 2016

Objectives

To evaluate the effect of suboptimal dosing on the outcomes of patients who received neoadjuvant chemotherapy (NAC) and robot‐assisted radical cystectomy (RARC).

Patients and Methods

We retrospectively reviewed 336 consecutive patients with urothelial carcinoma of the bladder who were treated with NAC and RARC at three academic institutions. Outcomes were compared among three groups: patients who received optimal NAC; patients who received suboptimal NAC; and those who did not receive NAC. To adjust for potential baseline differences between the three groups, propensity‐score‐based matching was performed. The suboptimal dose group was defined as those who received <3 cycles of cisplatin‐based chemotherapy, received a decreased dosage, or those not treated with cisplatin. Primary outcomes analysed were recurrence‐free survival (RFS) and overall survival (OS). Secondary outcomes were peri‐operative complications and readmissions after RARC.

Results

After propensity‐score matching, 69 patients in the cohort received optimal‐dose NAC, 41 received suboptimal NAC and 69 did not receive NAC. Complication rates and readmission rates did not differ significantly among the three groups. On multivariable analysis, suboptimal NAC and no NAC were independent predictors of worse RFS (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2–5.7, P = 0.01 and HR 2.4, 95% CI 1.28–5.16, P = 0.01) and worse OS (HR 4.5, 95% CI 1.6–15.0, P < 0.01 and HR 4.9, 95% CI 1.9–15.6, P < 0.01) in patients who received NAC and RARC. Failure to achieve pathological complete response (ypT0N0) was also an independent predictor of worse RFS (HR 6.6, 95% CI 1.3–20.9; P = 0.02) and OS (HR 4.9, 95% CI 1.8–15.3; P = 0.02).

Conclusion

Optimal NAC resulted in a better RFS and OS when compared with suboptimal or no NAC. Suboptimal and no NAC were associated with worse OS and RFS. These findings will facilitate improved patient counseling and treatment selection.
Adjuvant radiation therapy is associated with better oncological outcome compared with salvage radiation therapy in patients with pN1 prostate cancer treated with radical prostatectomy
Authors: Tilki Derya , Preisser Felix , Tennstedt Pierre , Tober Patrick , Mandel Philipp , Schlomm Thorsten , Steuber Thomas , Huland Hartwig , Schwarz Rudolf , Petersen Cordula , Graefen Markus , Ahyai Sascha
Published: October 2016

Objective

To analyse the comparative effectiveness of no treatment (NT) or salvage radiation therapy (sRT) at biochemical recurrence (BCR) vs adjuvant radiation therapy (aRT) in patients with lymph node (LN)‐positive prostate cancer (PCa) after radical prostatectomy (RP).

Patients and Methods

A total of 773 patients with LN‐positive PCa at RP, with or without additional radiation therapy (RT), in the period 2005–2013, were retrospectively analysed. Cox regression analysis was used to assess factors influencing BCR and metastasis‐free survival (MFS). Propensity score‐matched analyses were performed.

Results

The median follow‐up for the entire patient group was 33.8 months. Four‐year BCR‐free and MFS rates were 43.3% and 86.6%, respectively, for all patients. In multivariate analysis, NT/sRT (n = 505) was an independent risk factor for BCR and metastasis compared with aRT (n = 213). The superiority of aRT was confirmed after propensity score matching. The 4‐year MFS in the matched cohort was 82.5% vs 91.8% for the NT/sRT and aRT groups, respectively (P = 0.02). Early sRT (pre‐RT prostate‐specific antigen [PSA] ≤0.5 ng/mL) compared with sRT at PSA >0.5 ng/mL was significantly associated with a lower risk of metastasis.

Conclusion

Patients with LN‐positive PCa who received aRT had a significantly better oncological outcome than patients with NT/sRT, independent of tumour characteristics. Patients with early sRT had higher rates of response and better MFS than patients with pre‐RT PSA >0.5 ng/mL.
Tensins are versatile regulators of Rho GTPase signalling and cell adhesion
Authors: Blangy Anne
Published: October 2016

Tensins are focal adhesion molecules that were identified and characterised in the late 1980s to early 1990s. They play an essential role in the control of cell adhesion. Tensins can bind the tail of ß integrin via their phospho tyrosine binding domain, they exhibit various protein interaction domains including a Src Homology 2 domain and they are serine‐, threonine‐ and tyrosine‐phosphorylated in response to various stimuli. Tensins serve as scaffolds to gather signalling molecules at the extracellular matrix adhesion complexes. Tensins have emerged as important regulators of cell adhesion and migration, in particular by participating in Rho GTPase signalling pathways. Tensins were shown to influence the activity of the GTPase RhoA, by regulating the Rho GTPase activating protein Deleted in Liver Cancer 1. More recently, Tensin 3 was also found to regulate Dock5, a guanine nucleotide exchange factor for the GTPase Rac, and to modulate podosome‐based adhesion structures in osteoclasts. This review focusses on the recent literature highlighting how Tensins can interplay with regulators of Rho GTPase signalling pathways and how this influences cell adhesion and migration.
Antioxidants from black and green tea: from dietary modulation of oxidative stress to pharmacological mechanisms
Authors: Peluso Ilaria , Serafini Mauro
Published: October 2016

The consumption of tea (Camellia sinensis) has been correlated with a low incidence of chronic pathologies, such as cardiovascular disease and cancer, in which oxidative stress plays a critical role. Tea catechins and theaflavins are, respectively, the bioactive phytochemicals responsible for the antioxidant activity of green tea (GT) and black tea (BT). In addition to their redox properties, tea catechins and theaflavins could have also pharmacological activities, such as the ability to lower glucose, lipid and uric acid (UA) levels. These activities are mediated by pharmacological mechanisms such as enzymatic inhibition and interaction with transporters. Epigallocatechin gallate is the most active compound at inhibiting the enzymes involved in cholesterol and UA metabolism (hydroxy‐3‐methyl‐glutaryl‐CoA reductase and xanthine oxidase respectively) and affecting glucose transporters. The structural features of catechins that significantly contribute to their pharmacological effect are the presence/absence of the galloyl moiety and the number and positions of the hydroxyl groups on the rings. Although the inhibitory effects on α‐glucosidase, maltase, amylase and lipase, multidrug resistance 1, organic anion transporters and proton‐coupled folate transport occur at higher concentrations than those apparent in the circulation, these effects could be relevant in the gut. In conclusion, despite the urgent need for further research in humans, the regular consumption of moderate quantities of GT and BT can effectively modulate their antioxidant capacity, mainly in people subjected to oxidative stress, and could improve the metabolism of glucose, lipid and UA.

Linked Articles

This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
miR‐25‐3p reverses epithelial‐mesenchymal transition via targeting Sema4C in cisplatin‐resistance cervical cancer cells
Authors: Song Jing , Li Yue
Published: October 2016

Acquisition of epithelial‐mesenchymal transition (EMT) has recently been proposed as an important contributor of drug resistance in cervical cancer cells. However, the underlying mechanisms are still unclear. MicroRNAs play a crucial role in regulating EMT. The aim of this study was to explore the potential role of miR‐25‐3p in regulating EMT in cisplatin‐resistant (CR) cervical cancer cells. To this end, we established stable CR cervical cancer cells, HeLa‐CR and CaSki‐CR, and investigated the function of miR‐25‐3p in regulating EMT. It is found that CR cervical cancer cells possessed more EMT characteristics and demonstrated higher migratory abilities and invasiveness. miR‐25‐3p downregulation was also seen in HeLa‐CR and CaSki‐CR cells. Of note, ectopic expression of miR‐25‐3p reversed the EMT phenotype and sensitized CR cells to cisplatin via targeting Sema4C. Furthermore, stable overexpression of miR‐25‐3p in HeLa‐CR cells suppressed tumor growth in mice, downregulated Sema4C and Snail, and upregulated E‐cadherin compared with the control group. These results suggest that miR‐25‐3p is an important regulator of cervical cancer EMT and chemoresistance. Thus, upregulation of miR‐25‐3p could be a novel approach to treat cervical cancers that are resistant to chemotherapy.
Sleep Complaints and the 24‐h Melatonin Level in Individuals with Smith–Magenis Syndrome: Assessment for Effective Intervention
Authors: Spruyt Karen , Braam Wiebe , Smits Marcel , Curfs Leopold MG
Published: October 2016

Aims

Individuals with Smith–Magenis syndrome (SMS) are reported to have a disrupted circadian rhythm. Our aim was to examine problematic sleeping in those attending our sleep clinic for the first time.

Methods

At intake, caregivers of 50 children and nine adults with SMS were surveyed about the sleep pattern and potential melatonin administration. Sampling of salivary melatonin levels was performed.

Results

At intake, exogenous melatonin was used by 16 children (27.1% of sample; 56.3% male) with mean age 6.8 ± 2.8 years, whereas 34 children (57.6%; 7.5 ± 4.8 years old; 64.7% male) and nine adults (15.3%; 36.8 ± 15.3 years old; 44.4% male) were not taking melatonin at intake. Participants were reported to have problems with night waking and early awakenings regardless of melatonin administration. Overall, moderate to high levels of salivary melatonin at noon were found in individuals with SMS. In particular, children with SMS showed a disrupted melatonin pattern. Furthermore, the endogenous melatonin level, age, and gender may potentially interact, yielding the severity range of sleep disturbances reported in SMS.

Conclusion

Treatment of sleep problems in SMS is complex, and our findings may support person‐centered sleep and medication management. Future clinical trials including larger groups may shed light on such approaches.
Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage
Authors: Edwards JE , LaCerte C , Peyret T , Gosselin NH , Marier JF , Hofmann AF , Shapiro D
Published: October 2016

Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment. There was good agreement between predicted and observed increases in systemic OCA exposure in subjects with mild, moderate, and severe hepatic impairment, which were 1.4‐, 8‐, and 13‐fold relative to healthy volunteers. Predicted liver exposure for subjects with mild, moderate, and severe hepatic impairment were increased only 1.1‐, 1.5‐, and 1.7‐fold. In subjects with cirrhosis, OCA exposure in the liver, the primary site of pharmacological activity along with the intestine, is increased marginally (∼2‐fold).
Quantifying Beta‐Galactosylceramide Kinetics in Cerebrospinal Fluid of Healthy Subjects Using Deuterium Labeling
Authors: Kanhai KMS , Goulooze SC , Stevens J , Hay JL , Dent G , Verma A , Hankemeier T , de Boer T , Meijering H , Chavez JC , Cohen AF , Groeneveld GJ
Published: October 2016

Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid. Maximum deuterium enrichment of body water ranged from 1.5–3.9%, whereas that of galactosylceramide was much lower: 0.05–0.14%. This suggests a slow turnover rate, which was confirmed by the model‐estimated galactosylceramide turnover rate of 0.00168 day−1, which corresponds to a half‐life of 413 days. Additional studies in patients with multiple sclerosis are needed to investigate whether galactosylceramide turnover could be used as an outcome measure in clinical trials with remyelination therapies.
Vitamin D in hematological disorders and malignancies
Authors: Kulling Paige M. , Olson Kristine C. , Olson Thomas L. , Feith David J. , Loughran Thomas P.
Published: October 2016

Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti‐cancer therapy. Serum levels of 25(OH)D3, the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti‐cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti‐cancer therapies, and reduces the production of pro‐inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.
Dependence of Asian honeybee on deciduous woody plants for pollen resource during spring to mid‐summer in northern Japan
Authors: Fujiwara Ayumi , Washitani Izumi
Published: October 2016

Apis cerana japonica Radoszkowski, endemic to Japan, is known to be one of the most important pollinators for wild plants and crops, such as buckwheat, in cool to warm temperate Japan. To determine the degree of dependence of A. cerana japonica on forest resources, we analyzed pollen brought back to nests in a typical “Satoyama” landscape with relatively high deciduous forest coverage in northern Japan. We divided the landscape elements of the study area into three types: deciduous forest, conifer plantation and open land according to landcover digital data, and each pollen taxon was assigned to one of these three types of landscape elements. We collected total pollen loads of 15.75 g (total of colonies A and B) in May (spring), 1.57 g (total of colonies A and C) in June (early summer), 19.03 g (total of colonies A, B and C) in July (mid‐summer) and 45.61 g (total of colonies A, B and D) in September (autumn). Deciduous forests are the most important foraging habitats for A. cerana japonica in the “Satoyama” landscape especially from spring to mid‐summer when mass flowering of tall trees and shrubs species provides rich floral resources for developing bee colonies. On the other hand, the bees frequently foraged from herbaceous plant species in autumn when flowering of tree species reduces and herbaceous plant species have flowering peaks. In turn, the bees provide pollination services to a number of wild flowers blooming in various forest layers ranging from the canopy to the understory layer.
Crystal structure of a crustacean hyperglycemic hormone (CHH) precursor suggests structural variety in the C‐terminal regions of CHH superfamily members
Authors: Tsutsui Naoaki , Sakamoto Tatsuya , Arisaka Fumio , Tanokura Masaru , Nagasawa Hiromichi , Nagata Koji
Published: October 2016

The crustacean hyperglycemic hormone (CHH) is one of the major hormones in crustaceans, and peptides belonging to the CHH superfamily have been found in diverse ecdysozoans. Although the basic function of CHH is to control energy metabolism, it also plays various roles in crustacean species, such as in molting and vitellogenesis. Here, we present the crystal structure of Pej‐SGP‐I‐Gly, a partially active precursor of CHH from the kuruma prawn Marsupenaeus japonicus, which has an additional Gly residue in place of the C‐terminal amide group of the mature Pej‐SGP‐I. The 1.6‐angstrom crystal structure showed not only the common CHH superfamily scaffold comprising three α‐helices, three disulfide bridges, and a hydrophobic core but also revealed that the C‐terminal part has a variant backbone fold that is specific to Pej‐SGP‐I‐Gly. The α‐helix 4 of Pej‐SGP‐I‐Gly was much longer than that of molt‐inhibiting hormone (Pej‐MIH) from the same species, and as a result, the following C‐terminal helix, corresponding to α‐helix 5 in MIH, was not formed. Unlike monomeric Pej‐MIH, Pej‐SGP‐I‐Gly forms a homodimer in the crystal structure via its unique α‐helix 4. The unexpected dissimilar folds between Pej‐SGP‐I‐Gly and Pej‐MIH appear to be the result of their distinct C‐terminal amino acid sequences. Variations in amino acid sequences and lengths and the resulting variety of backbone folds allow the C‐terminal and sterically adjoining regions to confer different hormonal activities in diverse CHH superfamily members.

Database

Structural data are available in the PDB under the accession number 5B5I.
Insecticidal activity of a recombinant knottin peptide from Loxosceles intermedia venom and recognition of these peptides as a conserved family in the genus
Authors: Matsubara F. H. , Meissner G. O. , Herzig V. , Justa H. C. , Dias B. C. L. , Trevisan‐Silva D. , Gremski L. H. , Gremski W. , Senff‐Ribeiro A. , Chaim O. M. , King G. F. , Veiga S. S.
Published: October 2016

Loxosceles intermedia venom comprises a complex mixture of proteins, glycoproteins and low molecular mass peptides that act synergistically to immobilize envenomed prey. Analysis of a venom‐gland transcriptome from L. intermedia revealed that knottins, also known as inhibitor cystine knot peptides, are the most abundant class of toxins expressed in this species. Knottin peptides contain a particular arrangement of intramolecular disulphide bonds, and these peptides typically act upon ion channels or receptors in the insect nervous system, triggering paralysis or other lethal effects. Herein, we focused on a knottin peptide with 53 amino acid residues from L. intermedia venom. The recombinant peptide, named U2‐sicaritoxin‐Li1b (Li1b), was obtained by expression in the periplasm of Escherichia coli. The recombinant peptide induced irreversible flaccid paralysis in sheep blowflies. We screened for knottin‐encoding sequences in total RNA extracts from two other Loxosceles species, Loxosceles gaucho and Loxosceles laeta, which revealed that knottin peptides constitute a conserved family of toxins in the Loxosceles genus. The insecticidal activity of U2‐SCTX‐Li1b, together with the large number of knottin peptides encoded in Loxosceles venom glands, suggests that studies of these venoms might facilitate future biotechnological applications of these toxins.
An integration of mixed VND and VNS: the case of the multivehicle covering tour problem
Authors: Kammoun Manel , Derbel Houda , Ratli Mostapha , Jarboui Bassem
Published: October 2016

The multivehicle covering tour problem (m‐CTP) is a transportation problem with different kinds of locations, where a set of locations must be visited while another set must be close enough to planned routes. Given two sets of vertices V and W, where V represents the set of vertices that may be visited and W is a set of vertices that must be covered by up to m vehicles, the m‐CTP problem is to minimize vehicle routes on a subset of V including T, which represents the subset of vertices that must be visited through the use of potential locations in V. The variant of m‐CTP without a route‐length constraint is treated in this paper. To tackle this problem, we propose a variable neighborhood search heuristic based on variable neighborhood descent method. Experiments were conducted using the datasets based on traveling salesman problem library instances.
Pollinator adaptation and the evolution of floral nectar sugar composition
Authors: Abrahamczyk S. , Kessler M. , Hanley D. , Karger D. N. , Müller M. P. J. , Knauer A. C. , Keller F. , Schwerdtfeger M. , Humphreys A. M.
Published: October 2016

A long‐standing debate concerns whether nectar sugar composition evolves as an adaptation to pollinator dietary requirements or whether it is ‘phylogenetically constrained’. Here, we use a modelling approach to evaluate the hypothesis that nectar sucrose proportion (NSP) is an adaptation to pollinators. We analyse ~ 2100 species of asterids, spanning several plant families and pollinator groups (PGs), and show that the hypothesis of adaptation cannot be rejected:NSPevolves towards two optimal values, highNSPfor specialist‐pollinated and lowNSPfor generalist‐pollinated plants. However, the inferred adaptive process is weak, suggesting that adaptation toPGonly provides a partial explanation for how nectar evolves. Additional factors are therefore needed to fully explain nectar evolution, and we suggest that future studies might incorporate floral shape and size and the abiotic environment into the analytical framework. Further, we show thatNSPandPGevolution are correlated – in a manner dictated by pollinator behaviour. This contrasts with the view that a plant necessarily has to adapt its nectar composition to ensure pollination but rather suggests that pollinators adapt their foraging behaviour or dietary requirements to the nectar sugar composition presented by the plants. Finally, we document unexpectedly sucrose‐poor nectar in some specialized nectarivorous bird‐pollinated plants from the Old World, which might represent an overlooked form of pollinator deception. Thus, our broad study provides several new insights into how nectar evolves and we conclude by discussing why maintaining the conceptual dichotomy between adaptation and constraint might be unhelpful for advancing this field.
Multi‐Family Therapy with a Reflecting Team: A Preliminary Study on Efficacy among Opiate Addicts in Methadone Maintenance Treatment
Authors: Garrido‐Fernández Miguel , Marcos‐Sierra Juan A. , López‐Jiménez Ana , Ochoa de Alda Iñigo
Published: October 2016

In this study, we evaluate the efficacy of multi‐family therapy at reducing the addiction severity and at improving the psychological and family dynamics of opiate addicts receiving methadone treatment at a public treatment center. The study compares multi‐family therapy with a reflecting team (MFT‐RT) and a standard treatment following a methadone maintenance treatment program. The results show that multi‐family therapy with a reflecting team effectively reduces the addiction severity in several of the areas evaluated and noted that this effect is superior to standard treatment. The psychotherapy patients showed improvement in the areas of employment and social support; their drug use diminished and their psychiatric condition improved. At the same time, they needed a lower daily dose of methadone. In addition, the group undergoing standard treatment showed a noteworthy deterioration in their medical condition. Both groups showed a significant increase in their alcohol use. When applied to family treatments, the systemic‐constructivist approach by the reflecting team offers combined techniques that can help improve care for the families of patients with addiction problems.
THE ERRONEOUS USE OF CHINA'S POPULATION AND PER CAPITA DATA: A STRUCTURED REVIEW AND CRITICAL TEST
Authors: Gibson John , Li Chao
Published: October 2016

Hundreds of studies in economics misinterpret China's subnational population and per capita data. The most widely used population counts are of hukou registrations from each province, prefecture, county, or city rather than of the people living in each place and generating local gross domestic product. Over 220 million people have left their place of registration, while almost none had when reforms began, creating time‐varying errors in estimates of per capita income of subnational units. We survey empirical articles in blue ribbon journals, in development journals, and in regional and urban economics journals that use China's subnational data. Over 80% of articles use these data erroneously; most commonly the wrong population or employment counts are used to measure the size of subnational units, and per capita data are calculated with the wrong denominator for how variables are interpreted. We provide examples of errors from each group of journals, and a critical test of one highly cited study. Specifically, we show that if hukou registrations are erroneously used to measure the local population, following existing practice, conclusions about driving forces for urban area expansion are reversed. We give recommendations for more careful use of China's subnational population and per capita data.
Limited mouth opening in oral submucous fibrosis: reasons, ramifications, and remedies
Authors: Sharma Mohit , Radhakrishnan Raghu
Published: October 2016

Limited mouth opening (LMO) in oral submucous fibrosis (OSF) has been attributed to both the submucosal and muscle fibrosis (MF). While reflectory trismus was proposed before as an auxiliary mechanism by another group, the stretch‐mediated muscle damage (MSD), histopathological changes in blood vessels (such as endothelial dysfunction, endothelial hypertrophy, and endarteritis obliterans), and upregulated anaerobic isoforms of lactate dehydrogenase (LDH) have been proposed by us as complementary events leading to MF. Additionally, the amount of hypoxia‐mediated upregulation of anaerobic isoforms of LDH determines the extent of MF. Radiotherapy (RT)‐mediated release of reactive oxygen species causes vascular damage thereby worsening hypoxia. While the alteration in LDH levels secondary to hypoxia enhances fibrosis, RT worsens it. Oral squamous cell carcinoma occurring in the background of OSF is an absolute contraindication for RT as it augurs unfavorable prognosis. An algorithm to demonstrate this with evidence is clearly depicted. The role of HIF‐1α in the progression of OSF and its malignant transformation, and the consideration of hyperbaric oxygen therapy as a therapeutic remedy in OSF are underscored.
Studying interactions between excavating sponges and massive corals by the use of hybrid cores
Authors: Fang James K. H. , Mason Robert A. B. , Schönberg Christine H. L. , Hoegh‐Guldberg Ove , Dove Sophie
Published: October 2016

Excavating sponges often compete with reef‐building corals. To study sponge–coral interactions, we devised a design of hybrid cores that allows sponges and corals to be arranged side by side with similar size and shape, mimicking the situation of neighbouring organisms. Compared to earlier methods that attached sponge cores onto coral surfaces, hybrid cores provide an opportunity to study organism interactions under conditions more equal to the interacting partners. The use of hybrid cores was demonstrated for the excavating sponge Cliona orientalis and the massive coral Porites, which commonly interact on the Great Barrier Reef. Cliona orientalis and massive Porites were cut into half‐moon shaped explants and combined as hybrid cores under replicate conditions. After 90 days in an aquarium setting, positive growth of Cl. orientalis along with net bioerosion were observed in sponge control cores that combined Cl. orientalis with blank substrate. However, when Cl. orientalis and massive Porites were in contact in interaction cores, the sponge displayed negative growth and undetectable bioerosion, and was slightly overgrown by the coral. Cliona orientalis may have developed tissue extension beneath the living coral tissue, but growth and net calcification rates of massive Porites were apparently not affected by Cl. orientalis when comparing the interaction cores to coral control cores that combined massive Porites with blank substrate. Overall, the present work demonstrated that hybrid cores can be used to generate conditions suitable for studying sponge–coral interactions in the laboratory, which can also be applied in the field.
Symbiosis between the holothurian Scotoplanes sp. A and the lithodid crab Neolithodes diomedeae on a featureless bathyal sediment plain
Authors: Barry James P. , Taylor Josi R. , Kuhnz Linda A. , De Vogelaere Andrew P.
Published: October 2016

Vulnerability to predation may be high for many megafaunal taxa in deep‐sea sedimentary habitats where physical heterogeneity is low. During ROV observations in a bathyal sediment plain off Central California, juveniles of the lithodid crab Neolithodes diomedeae were frequently observed on or under the holothurian (sea cucumber) Scotoplanes sp. A, and are hypothesized to benefit from this association as a nursery or refugium from predation. Ninety‐six percent (n = 574 of 599) of the juvenile N. diomedeae observed (density varied from 0.02–0.75/m2 among sites and seasons) in the study area were associated with Scotoplanes sp. A. Of the 2596 Scotoplanes sp. A observed (density varied from 0.48 to 25.90/m2), 22% were attended by at least one juvenile crab, and rarely two crabs (n = 4). Solitary N. diomedeae were rarely observed. This decapod–holothurian symbiosis appears to be largely commensal, with juvenile crabs (carapace width = 0.03–0.31 ×  holothurian length) observed on or beneath Scotoplanes sp. A in a habitat with few refugia from epibenthic predators. Other hypotheses may explain or enhance the potential benefits of the association for N. diomedeae, such as elevated food availability due to the activities of Scotoplanes sp. A. The relationship may be mutualistic if there is a benefit for the holothurian, including the removal of epizoic parasites. Ultimately, the nursery or other effects on the population dynamics of N. diomedeae may be minimal in low‐relief, sediment‐dominated habitats, as very few sub‐adult crabs were observed in the study area and were likely consumed upon outgrowing their refugia. While sedimentary habitats may be a sink for N. diomedeae populations, growth of juvenile crabs during their association with Scotoplanes sp. A should increase energy flow to its predator populations. This association has not been reported previously but may be expected in sediment‐dominated habitats where these species overlap.
Salmonella enterica synthesizes 5,6‐dimethylbenzimidazolyl‐(DMB)‐α‐riboside. Why some Firmicutes do not require the canonical DMB activation system to synthesize adenosylcobalamin
Authors: Mattes Theodoric A. , Escalante‐Semerena Jorge C.
Published: October 2016

5,6‐Dimethylbenzimidazolyl‐(DMB)‐α‐ribotide [α‐ribazole‐5′‐phosphate (α‐RP)] is an intermediate in the biosynthesis of adenosylcobalamin (AdoCbl) in many prokaryotes. In such microbes, α‐RP is synthesized by nicotinate mononucleotide (NaMN):DMB phosphoribosyltransferases (CobT in Salmonella enterica), in a reaction that is considered to be the canonical step for the activation of the base of the nucleotide present in adenosylcobamides. Some Firmicutes lack CobT‐type enzymes but have a two‐protein system comprised of a transporter (i.e., CblT) and a kinase (i.e., CblS) that can salvage exogenous α‐ribazole (α‐R) from the environment using CblT to take up α‐R, followed by α‐R phosphorylation by CblS. We report that Geobacillus kaustophilus CblT and CblS proteins restore α‐RP synthesis in S. enterica lacking the CobT enzyme. We also show that a S. enterica cobT strain that synthesizes GkCblS ectopically makes only AdoCbl, even under growth conditions where the synthesis of pseudoCbl is favored. Our results indicate that S. enterica synthesizes α‐R, a metabolite that had not been detected in this bacterium and that GkCblS has a strong preference for DMB‐ribose over adenine‐ribose as substrate. We propose that in some Firmicutes DMB is activated to α‐RP via α‐R using an as‐yet‐unknown route to convert DMB to α‐R and CblS to convert α‐R to α‐RP.
Advances in biologic augmentation for rotator cuff repair
Authors: Patel Sahishnu , Gualtieri Anthony P. , Lu Helen H. , Levine William N.
Published: October 2016

Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon‐to‐bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue. Therefore, various biological augmentation approaches have been investigated to improve rotator cuff repair healing. This review highlights recent advances in three fundamental approaches for biological augmentation for functional and integrative tendon–bone repair. First, the exploration, application, and delivery of growth factors to improve regeneration of native tissue are discussed. Second, applications of stem cell and other cell‐based therapies to replenish damaged tissue for better healing are covered. Finally, this review will highlight the development and applications of compatible biomaterials to both better recapitulate the tendon–bone interface and improve delivery of biological factors for enhanced integrative repair.
Dispositional optimism as predictor of outcome in short‐ and long‐term psychotherapy
Authors: Heinonen Erkki , Heiskanen Tiia , Lindfors Olavi , Härkäpää Kristiina , Knekt Paul
Published: October 2016

Objectives

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients’ ability to benefit from short‐term versus long‐term psychotherapy.

Design

A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short‐term (solution‐focused or short‐term psychodynamic) or long‐term psychodynamic therapy and followed up for 3 years.

Methods

Dispositional optimism was assessed by patients at baseline with the self‐rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow‐up, in terms of depressive (BDI, HDRS), anxiety (SCL‐90‐ANX, HARS), and general psychiatric symptoms (SCL‐90‐GSI), all seven follow‐up points including patients’ self‐reports and three including interview‐based measures.

Results

Lower dispositional optimism predicted faster symptom reduction in short‐term than in long‐term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long‐term, as compared to short‐term, psychotherapy.

Conclusions

Weaker optimism appeared to predict sustenance of problems early in long‐term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long‐term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine‐tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities.

Practitioner points

Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery.

Patients with weaker optimism do not seem to gain added benefits from long‐term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long‐term therapy.
The host plant Pinus pinaster exerts specific effects on phosphate efflux and polyphosphate metabolism of the ectomycorrhizal fungus Hebeloma cylindrosporum: a radiotracer, cytological staining and 31P NMR spectroscopy study
Authors: Torres‐Aquino Margarita , Becquer Adeline , Le Guernevé Christine , Louche Julien , Amenc Laurie K , Staunton Siobhan , Quiquampoix Hervé , Plassard Claude
Published: October 2016

Ectomycorrhizal (ECM) association can improve plant phosphorus (P) nutrition. Polyphosphates (polyP) synthesized in distant fungal cells after P uptake may contribute to P supply from the fungus to the host plant if they are hydrolyzed to phosphate in ECM roots then transferred to the host plant when required. In this study, we addressed this hypothesis for the ECM fungus Hebeloma cylindrosporum grown in vitro and incubated without plant or with host (Pinus pinaster) and non‐host (Zea mays) plants, using an experimental system simulating the symbiotic interface. We used 32P labelling to quantify P accumulation and P efflux and in vivo and in vitro nuclear magnetic resonance (NMR) spectroscopy and cytological staining to follow the fate of fungal polyP. Phosphate supply triggered a massive P accumulation as newly synthesized long‐chain polyP in H. cylindrosporum if previously grown under P‐deficient conditions. P efflux from H. cylindrosporum towards the roots was stimulated by both host and non‐host plants. However, the host plant enhanced 32P release compared with the non‐host plant and specifically increased the proportion of short‐chain polyP in the interacting mycelia. These results support the existence of specific host plant effects on fungal P metabolism able to provide P in the apoplast of ectomycorrhizal roots.
Impact of social capital on psychological distress and interaction with house destruction and displacement after the Great East Japan Earthquake of 2011
Authors: Tsuchiya Naho , Nakaya Naoki , Nakamura Tomohiro , Narita Akira , Kogure Mana , Aida Jun , Tsuji Ichiro , Hozawa Atsushi , Tomita Hiroaki
Published: October 2016

Aim

Social capital has been considered an important factor affecting mental‐health outcomes, such as psychological distress in post‐disaster settings. Although disaster‐related house condition and displacement could affect both social capital and psychological distress, limited studies have investigated interactions. This study aimed to examine the association between social capital and psychological distress, taking into consideration the interaction of disaster‐related house condition after the Great East Japan Earthquake of 2011.

Methods

Using data from 3793 adults living in Shichigahama, Miyagi Prefecture, Japan, we examined the association between social capital measured by generalized trust and psychological distress measured by the Kessler 6 scale. We conducted stratified analysis to investigate an interaction of house destruction and displacement. Multivariate analyses taking into consideration the interaction were performed.

Results

In the crude analysis, low social capital (odds ratio [OR] 4.46; 95% confidence interval [CI], 3.27–6.07) and large‐scale house destruction (OR 1.96; 95%CI, 1.47–2.62) were significantly associated with psychological distress. Stratified analyses detected an interaction with house destruction and displacement (P for interaction = 0.04). Multivariate analysis with interaction term revealed that individuals with low social capital, large‐scale house damage, and displacement were at greater risk of psychological distress, corresponding to adjusted OR of 5.78 (95%CI, 3.48–9.60).

Conclusion

In the post‐disaster setting, low social capital increased the risk of psychological distress, especially among individuals who had large‐scale house destruction. Among the participants with severe disaster damage, high social capital would play an important role in protecting mental health.
Paroxysmal atrioventricular block after heart transplantation in children: an early sign of rejection?
Authors: Grutter Giorgia , Alfieri Sara , Calcagni Giulio , Castelluzzo Maria Assunta , Silvetti Massimo Stefano , Parisi Francesco , Drago Fabrizio
Published: October 2016

In OHT recipients, pathologic evaluation of the heart during acute rejection can show involvement of both the conduction system and the myocardium. We here describe the cases of a 9‐year‐old male with DCM and a 13‐year‐old female with RCM, who developed third‐degree PAVB associated with acute rejection 36 months and 24 months after OHT, respectively. We conclude that PAVB could be considered an early sign of acute rejection after OHT in children who exhibit post‐transplantation presyncope or syncope.
Resiniferatoxin lowers TNF‐α, NO and PGE2 in the intestinal phase and the parasite burden in the muscular phase of Trichinella spiralis infection
Authors: Muñoz‐Carrillo J. L. , Muñoz‐Escobedo J. J. , Maldonado‐Tapia C. H. , Chávez‐Ruvalcaba F. , Moreno‐García M. A.
Published: October 2016

During the course of infection with Trichinella spiralis, an inflammatory response is triggered at the intestinal level in the host, playing a crucial role in the expulsion and elimination of the parasite. However, several studies have demonstrated that this inflammatory response is harmful to the host; hence, the importance of studying molecules with therapeutic potential like resiniferatoxin, which is known to have an anti‐inflammatory effect both in vitro and in vivo. In this article, we evaluated the anti‐inflammatory activity of resiniferatoxin during the intestinal phase of T. spiralis infection by quantitatively determining the levels of TNF‐α, NO and PGE2 as well as the percentage of eosinophils in the blood and intestinal pathology. In addition, parasite burden was determined during the muscle infection. Our results show that resiniferatoxin lowered the serum levels of TNF‐α, NO and PGE2, as well as the percentage of eosinophils in the blood and intestinal pathology during the intestinal infection. Moreover, resiniferatoxin also lowered the parasite burden in muscle, resulting in a reduction of the humoral response (IgG) associated to treatment with resiniferatoxin. These findings suggest a potential therapeutic use of the anti‐inflammatory effect of resiniferatoxin, which also contributes to host defence against the challenge of T. spiralis infection.
Mucosal and systemic immune modulation by Trichuris trichiura in a self‐infected individual
Authors: Dige A. , Rasmussen T. K. , Nejsum P. , Hagemann‐Madsen R. , Williams A. R. , Agnholt J. , Dahlerup J. F. , Hvas C. L.
Published: October 2016

Helminthic therapy of immune‐mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self‐infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T‐helper (h)1‐, Th2‐, Th17‐ and Treg‐associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti‐Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2‐dominated T cell response at the expense of the Th1‐response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity.
Consistent action of two partially effective loci conferring resistance to Globodera pallida Pa2/3 across multiple nematode field populations
Authors: Rigney B. , Blok V. , Griffin D. , Dalton E. , Milbourne D.
Published: October 2016

The potato cyst nematodes (PCN) Globodera rostochiensis and Globodera pallida are significant pests of potatoes worldwide. The most effective control methods are crop rotation and the deployment of resistant varieties. Complete resistance to G. rostochiensis based on a single resistance gene has successfully been integrated into many varieties. However, resistance to G. pallida has not been as successful to date, with current varieties only exhibiting partial resistance. Combining partially effective quantitative trait loci (QTLs) for resistance can increase the strength and breadth of the resistance. An additive effect on resistance has previously been demonstrated on combining two QTLs from Solanum tuberosum subsp. andigena (GpaIVsadg) and Solanum vernei (Gpa5). However, populations of G. pallida can be quite divergent and it was unclear whether the relative effects of the individual QTLs and the combined additive effect would be consistent across different G. pallida Pa2/3 populations. Using a mapping population segregating for both QTLs, the effect of the QTLs individually and combined was examined on four UK‐derived field populations of G. pallida pathotype Pa2/3, and the relative effects of the individual QTLs and the additive effect of the combination found to be consistent across all populations.
Contrasting environmental effects of astronomically driven climate change on three Eocene hemipelagic successions from the Basque–Cantabrian Basin
Authors: Martínez‐Braceras Naroa , Payros Aitor , Miniati Francesco , Arostegi Javier , Franceschetti Gloria
Published: October 2016

Several processes can contribute to the formation of hemipelagic limestone–marl alternations as a consequence of astronomically driven climate change. The aim of this study was to decipher which environmental factors governed the formation of three Eocene hemipelagic successions of the Basque–Cantabrian Basin using a comprehensive set of physical and bulk carbonate geochemical data (bed thickness, mineralogy, %CaCO3, δ13C and δ18O). The results show that the significance of several environmental processes varied depending on the palaeogeographic setting and eccentricity‐modulated precessional seasonality. In the Sopelana starved deep‐sea basin, limestones were formed as a consequence of high pelagic carbonate productivity during periods of warm seawater and sluggish circulation, which corresponded with periods of low seasonality (summers at aphelion); conversely, marls accumulated when pelagic carbonate productivity decreased during periods with cooler waters and more vigorous circulation, which occurred when seasonality was higher (summers at perihelion). In the Gorrondatxe submarine fan fringe, marls accumulated when high seasonality produced significant continental rainfall and run‐off, causing the dilution of pelagic carbonate sedimentation with terrigenous supplies. In the Oyambre upper slope, marls also accumulated when seasonality was high, as pelagic carbonate productivity decreased due to both the expansion of low‐salinity waters on the ocean surface and the increase in continentally derived nutrients, which caused detrimental seawater conditions for calcareous plankton. Both in Gorrondatxe and Oyambre, limestones accumulated when boreal summer at aphelion caused low seasonality, which allowed relatively stable conditions to prevail. At minimum eccentricity, when precession‐driven seasonality contrast diminished, changes in pelagic carbonate productivity were significant in the three sections. On the contrary, at maximum eccentricity, when seasonality peaked due to summers occurring at perihelion, the effects of other environmental processes, such as continental and oceanic currents, became influential. However, the influence of these processes minimized when summertime coincided with aphelion at maximum eccentricity and seasonality was weakest.