bluuebunny/crossref_metadata_2025 huggingface dataset:
Flood pulses drive the temporal dynamics of assemblages of aquatic insects (Heteroptera and Coleoptera) in a temperate floodplain
Authors: Turić Nataša , Temunović Martina , Radović Andreja , Vignjević Goran , Sudarić Bogojević Mirta , Merdić Enrih
Published: July 2015

Lowland riverine floodplains are among the most dynamic and heterogeneous of ecosystems, but many have been extensively modified. Their provision of important habitats provides a key motivation for restoring natural flow regimes (in terms of magnitude, frequency, duration, timing and rate of change of hydrological conditions). Despite general recognition that aquatic insects respond to changes in water availability, there is little agreement about the influence of flow regime components on community structure in floodplains.

We analysed a 6‐year (2005 and 2007–2011) data set of aquatic insects (Heteroptera and Coleoptera) in a large Danubian floodplain characterised by pronounced hydrological variability. We hypothesised that abundance and assemblage structure would depend on flow regime components. In particular, we predicted that high‐flow events in the mainstream and concurrent high‐magnitude floods of prolonged duration would have a positive effect on diversity and abundance and that insect assemblages would differ between phases of hydrological connectivity. In addition, we assessed whether the survival of two threatened aquatic insects,Graphoderus bilineatusandBerosus geminus, depends on hydrological connectivity.

Abundance and species richness of Heteroptera and Coleoptera increased during years with frequent extremely high flood pulses and prolonged flooding. Multivariate ordination showed subtle relationships between hydrological conditions, hydrological connectivity and insect assemblages with number of days in flood providing the best fit. Spring floods had a more pronounced effect on the assemblages than autumn floods. The time lag between flood occurrence and its apparent effect on aquatic insects was 17–31 days, reflecting insect life cycles.

The abundance ofG. bilineatus(Coleoptera: Dytiscidae) was affected by mean water level during the month preceding sampling, whereas the abundance ofB. geminus(Coleoptera: Hydrophilidae) was related to the occurrence of prolonged high‐magnitude floods.

The current water regime of the Danube River favours generalist species with high dispersal capacities and broad niches and food resources. Changes in flow management practices could remove the positive influence of floods on aquatic insect communities and lead to losses of threatened species that depend on these river–floodplain habitats. Our results contribute to the understanding necessary for appropriate evaluation and prioritisation of international floodplain conservation efforts.
Influence of corn, switchgrass, and prairie cropping systems on soil microbial communities in the upper Midwest of the United States
Authors: Jesus Ederson da C. , Liang Chao , Quensen John F. , Susilawati Endang , Jackson Randall D. , Balser Teresa C. , Tiedje James M.
Published: June 2015

Because soil microbes drive many of the processes underpinning ecosystem services provided by soils, understanding how cropping systems affect soil microbial communities is important for productive and sustainable management. We characterized and compared soil microbial communities under restored prairie and three potential cellulosic biomass crops (corn, switchgrass, and mixed prairie grasses) in two spatial experimental designs – side‐by‐side plots where plant communities were in their second year since establishment (i.e., intensive sites) and regionally distributed fields where plant communities had been in place for at least 10 years (i.e., extensive sites). We assessed microbial community structure and composition using lipid analysis, pyrosequencing of rRNA genes (targeting fungi, bacteria, archaea, and lower eukaryotes), and targeted metagenomics of nifH genes. For the more recently established intensive sites, soil type was more important than plant community in determining microbial community structure, while plant community was the more important driver of soil microbial communities for the older extensive sites where microbial communities under corn were clearly differentiated from those under switchgrass and restored prairie. Bacterial and fungal biomasses, especially biomass of arbuscular mycorrhizal fungi, were higher under perennial grasses and restored prairie, suggesting a more active carbon pool and greater microbial processing potential, which should be beneficial for plant acquisition and ecosystem retention of carbon, water, and nutrients.
Differential expression of immunohistochemical markers in primary lung and breast cancers enriched for triple‐negative tumours
Authors: Provenzano Elena , Byrne David J , Russell Prudence A , Wright Gavin M , Generali Daniele , Fox Stephen B
Published: June 2015

Aims

In breast cancer patients presenting with a lung lesion, the distinction between lung and breast origin is clinically important. Lung and breast cancers are both CK7+/CK20−, so additional immunohistochemical markers are needed.

Methods and results

We examined the expression of oestrogen receptor (ER), progesterone receptor (PR), thyroid transcription factor‐1 (TTF‐1), gross cystic disease fluid protein‐15 (GCDFP‐15), p63 and Wilms’ tumour 1 (WT1) in a series of tissue microarrays comprising 266 non‐small‐cell lung cancers and 837 primary breast cancers enriched for triple‐negative tumours (TNBC). Staining for ER, PR, TTF‐1 and GCDFP‐15 was present in 63%, 49%, 0% and 25% of breast and 6%, 9%, 59% and 1% of lung cancers, respectively. Strong staining for p63 was present in 63 (97%) lung squamous cell carcinomas and only eight (9%) TNBC. WT1 nuclear staining was rare; however, cytoplasmic staining was identified in 49 (40%) TNBC and 10 (5%) lung cancers. Cluster analysis segregated TNBC from lung cancers with TTF‐1 and/or p63 staining favouring lung origin, and GCDFP‐15 or WT1 staining favouring breast origin. Cancers negative for all four markers (17%) were 60% breast and 40% lung origin.

Conclusion

An immunohistochemical panel incorporating ER, TTF‐1, GCDFP‐15, p63 and WT1 can help to distinguish lung cancer from metastatic breast cancer, including TNBC.
Crystal‐storing histiocytosis: a clinicopathological study of 13 cases
Authors: Kanagal‐Shamanna Rashmi , Xu‐Monette Zijun Y , Miranda Roberto N , Dogan Ahmet , Zou Dehui , Luthra Rajyalakshmi , Weber Donna M. , O'Malley Dennis P , Jorgensen Jeffrey L , Khoury Joseph D , Bueso‐Ramos Carlos E , Orlowski Robert Z , Medeiros L. Jeffrey , Young Ken H
Published: June 2015

Aims

Crystal‐storing histiocytosis (CSH) is a rare lesion composed of histiocytes with abnormal intralysosomal accumulation of immunoglobulin (Ig) as crystals, reported in patients with plasmacytic/lymphoplasmacytic neoplasms. The aims of this study were to report the clinicopathological features of 13 patients with CSH, and to describe the proteomic composition of the crystals in three cases analysed by mass spectrometry (MS).

Methods and results

There were seven men and six women, with a median age of 60 years (range, 33–79 years). CSH was generalized in one patient (8%) and localized in 12 (92%) patients, involving various sites. CSH was associated with a low‐grade B‐cell lymphoma with plasmacytoid differentiation or a plasma cell neoplasm in all cases. In 10 (77%) cases, CSH represented >50% of the neoplastic infiltrate. According to immunohistochemical studies, histiocytes were positive for monotypic kappa in 5 (50%) cases, and for monotypic lambda in 4 (40%) cases; in 1 (10%) case, the results were equivocal. MS analysis of the histiocyte contents in all three tested cases showed a predominance of variable‐region fragments of Ig light and/or heavy chains.

Conclusions

CSH is frequently associated with an underlying lymphoplasmacytic neoplasm. MS findings suggest that Ig alterations and/or possibly defects in the ability of histiocytes to process Ig play a role in pathogenesis.
In vivo topical application of acetyl aspartic acid increases fibrillin‐1 and collagen IV deposition leading to a significant improvement of skin firmness
Authors: Gillbro J. M. , Merinville E. , Cattley K. , Al‐Bader T. , Hagforsen E. , Nilsson M. , Mavon A.
Published: July 2015

Synopsis

Objective

Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A‐A‐A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F‐actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in‐use trial demonstrated that 1% A‐A‐A was well tolerated. In this study, the aim was to investigate whether A‐A‐A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study.

Method

Two separate double‐blind vehicle‐controlled in vivo studies were conducted using a 1% A‐A‐A containing oil‐in‐water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12‐day treatment of A‐A‐A on collagen IV (COLIV) and fibrillin‐1. In a subsequent pilot study, 0.1% retinol was used for comparison to A‐A‐A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness.

Results

Twelve‐day topical application of 1% A‐A‐A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A‐A‐A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A‐A‐A. However, only A‐A‐A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A‐A‐A as a skin‐firming active ingredient.

Conclusion

In this study, we showed the in vivo efficacy of 1% A‐A‐A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti‐ageing ‘cosmeceutical’ ingredient answering the needs of our key consumer base.
New Aluminosilicate Glasses as High‐Power Laser Materials
Authors: Herrmann Andreas , Rüssel Christian
Published: July 2015

In the past few years, aluminosilicate glasses of an extremely broad compositional range have been prepared and analyzed to scan this glass type for its potential use as high‐power laser material. The tested network modifier ions included Li+, Na+, K+, Mg2+, Ca2+, Sr2+, Ba2+, Zn2+, Pb2+, Y3+, and La3+. Preliminary investigations have been conducted with Sm3+‐ and Eu3+‐doped glasses; selected glass compositions have also been prepared with Yb3+ doping for laser testing. It has been found that low refractive indices/low average molecular weights/low densities of the glasses in most cases support relatively long fluorescence lifetimes of the doped ions. It was further concluded that the phonon energy of the molecular network of the glasses does not affect the fluorescence properties of the doped samples. The mechanical properties such as Young's modulus, Vickers hardness, and fracture toughness generally increase with increasing field strength of the network modifier ion for constant stoichiometric ratios of the glass components. The lowest potential thermal stress values were found for zinc and magnesium aluminosilicate glasses, which also have relatively high field strengths. Taking all these facts into account, a ternary lithium aluminosilicate and a mixed lithium magnesium aluminosilicate glass doped with Yb3+ have been prepared in high optical quality and tested with respect to their laser performance. The fluorescence lifetime values are somewhat lower than in well‐established Yb3+‐doped laser materials, such as fluoride phosphate glass or single crystalline calcium fluoride. Nevertheless, the aluminosilicate glasses show exceptionally high absorption and emission cross sections, smooth and very broad amplification profiles, as well as much better thermomechanical properties. Quantum efficiencies close to unity could be reached by consequently removing dissolved OH from the glass melt.
Mathematical model reveals how regulating the three phases of T‐cell response could counteract immune evasion
Authors: Lorenzi Tommaso , Chisholm Rebecca H. , Melensi Matteo , Lorz Alexander , Delitala Marcello
Published: June 2015

T cells are key players in immune action against the invasion of target cells expressing non‐self antigens. During an immune response, antigen‐specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen‐specific T cells. The succession of these reciprocal selective sweeps can result in ‘chase‐and‐escape’ dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen‐specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long‐lived memory reservoir, using dual immunotherapies based on the cytokines interleukin‐7 and/or interleukin‐15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.
H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses
Authors: Bidula Stefan , Sexton Darren W. , Yates Matthew , Abdolrasouli Alireza , Shah Anand , Wallis Russell , Reed Anna , Armstrong‐James Darius , Schelenz Silke
Published: July 2015

Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H‐Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H‐ficolin in fungal defence. Additionally, we investigated the presence of H‐ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H‐Ficolin exhibited demonstrable binding to A. fumigatus conidia via l‐fucose, d‐mannose and N‐acetylglucosamine residues in a calcium‐ and pH‐dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H‐ficolin opsonization manifested an increase in interleukin‐8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen‐activated protein kinase MAPK kinase 1/2, p38 MAPK and c‐Jun N‐terminal kinase. Finally, H‐ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H‐ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H‐ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.
How mechanisms of habitat preference evolve and promote divergence with gene flow
Authors: Berner D. , Thibert‐Plante X.
Published: June 2015

Habitat preference may promote adaptive divergence and speciation, yet the conditions under which this is likely are insufficiently explored. We use individual‐based simulations to study the evolution and consequence of habitat preference during divergence with gene flow, considering four different underlying genetically based behavioural mechanisms: natal habitat imprinting, phenotype‐dependent, competition‐dependent and direct genetic habitat preference. We find that the evolution of habitat preference generally requires initially high dispersal, is facilitated by asymmetry in population sizes between habitats, and is hindered by an increasing number of underlying genetic loci. Moreover, the probability of habitat preference to emerge and promote divergence differs greatly among the underlying mechanisms. Natal habitat imprinting evolves most easily and can allow full divergence in parameter ranges where no divergence is possible in the absence of habitat preference. The reason is that imprinting represents a one‐allele mechanism of assortative mating linking dispersal behaviour very effectively to local selection. At the other extreme, direct genetic habitat preference, a two‐allele mechanism, evolves under restricted conditions only, and even then facilitates divergence weakly. Overall, our results indicate that habitat preference can be a strong reproductive barrier promoting divergence with gene flow, but that this is highly contingent on the underlying preference mechanism.
Humidity affects populations of Drosophila suzukii (Diptera: Drosophilidae) in blueberry
Authors: Tochen S. , Woltz J. M. , Dalton D. T. , Lee J. C. , Wiman N. G. , Walton V. M.
Published: July 2015

Temperature and humidity affect insect physiology, survival, fecundity, reproductive status and behaviour. Complementing previous work investigating the effects of temperature on adult survival and fecundity of the invasive frugivorous pest, Drosophila suzukii (Matsumura), this study was conducted to determine the effect of humidity on D. suzukii larval development, adult survival, fecundity and reproductive status using blueberry as a host substrate. The five constant humidity levels in laboratory bioassays were 20, 33, 71, 82 and 94% RH at 20.6 ± 0.2°C. As RH increased, fecundity and longevity increased. At the higher humidity levels, RH had limited impact on mean generation times (T), larval development and eclosion times. The highest net reproductive rate (Ro = 68) and highest intrinsic rate of population increase (rm = 0.17) were both recorded at 94% RH. The reproductive status of females, as indicated by the number of mature oocytes per female, was significantly greater at 82 and 94% RH, compared to 71% RH. In addition to the laboratory procedures, we correlated field trap captures over an 81‐day summer period to relative humidity (RH) levels in close proximity to those traps. In the field, low ambient humidity levels resulted in decreased trap captures. A humidity‐dependent population model predicted lower densities of D. suzukii relative to populations at higher humidity. This study supports the hypothesis that cultural practices that minimize lower humidity levels in crops can contribute to the management of D. suzukii. Such methods may include open pruning, drip irrigation and field floor management.
Efficacy of Some Essential Oil Components as Food Preservatives Against Food Contaminating Molds, Aflatoxin B1 Production and Free Radical Generation
Authors: Prakash Bhanu , Mishra Prashant Kumar , Kedia Akash , Dwivedy Abhishek Kumar , Dubey N.K.
Published: July 2015

This study explores the efficacy of essential oil components, viz. Z‐citral, E‐citral, methyl cinnamate and fenchone individually and in combination (1:1:1:1), against food contaminating molds, aflatoxin B1 production and as antioxidant. The oil components (except fenchone) and their combination inhibited the aflatoxigenic strain of Aspergillus flavus (LHP‐10) and 13 additional food‐infesting molds at minimum inhibitory concentration ranging between 0.50 and 5.25 μL/mL while aflatoxin production inhibited between 0.6 and 2.50 μL/mL. Methyl cinnamate showed the highest antifungal and anti‐aflatoxigenic activity followed by the combination, Z‐citral, E‐citral and fenchone. The oil components exhibited synergistic action during antioxidant activity as the oil combination was substantially superior (IC50 value 5.89 μL/mL) to the sum of the individual antioxidant effects. The antifungal mechanism of action of components and their combination was studied by measuring the ergosterol content in the plasma membrane of mold species. During in vivo experiments in storage containers, the oil combination provided >50% protection of chickpea samples against fungal infestation up to 6 months of storage without affecting their viability.

Practical Applications

Based on the results of the present investigation, some essential oil components and their combination may be recommended as plant‐based preservatives in view of their antifungal activity against food‐infesting molds, aflatoxin secretion and as antioxidant. The efficacy of the components in protecting the fungal contamination of chickpea samples during storage condition without affecting their viability strengthens their formulation for practical application. The study recommends some essential oil components to food and agri‐industries as safer alternatives of synthetic preservatives in view of their adverse effects on consumer's health and environment.
Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity
Authors: Beveridge Claire , Knutson Kristen , Spampinato Lisa , Flores Andrea , Meltzer David O. , Van Cauter Eve , Arora Vineet M.
Published: July 2015

Objectives

To assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity.

Design

Prospective cohort study.

Setting

University of Chicago Medical Center general medicine wards.

Participants

Community‐dwelling inpatients aged 50 and older (N = 120)

Measurements

Physical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random‐effects linear regression analysis was used to examine the association between in‐hospital sleep and physical activity.

Results

From March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51–121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50–75; youngest quartile 121, 95% CI = 98–145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60–83; lowest tertile 125, 95% CI = 104–147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = −5.65 to −0.43, P = .02) for each additional hour of inpatient sleep.

Conclusion

Older, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community.
Chandipura virus perturbs cholesterol homeostasis leading to neuronal apoptosis
Authors: Ghosh Sourish , Mukherjee Sriparna , Basu Anirban
Published: June 2015

Chandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) induces neuronal death through the Fas‐mediated extrinsic apoptosis pathway. What propels this apoptosis remains unclear, although oxysterols have been reported to be key players in neurodegeneration. In our study of CHPV‐infected brain samples, we observed over‐expression of genes such as apolipoprotein E, Cyp46a1, Srebf‐1 and Nsdhl. This backs up the hypothesis that CHPV replication demands cholesterol that is supplied by apolipoprotein E through low density lipid receptors, lipid metabolism being pivotal for viral replication. We were able to illustrate this with over‐expression of low density lipid receptors in CHPV‐infected neurons. An upsurge of cholesterol concentration has been observed in neurons, triggering the expression of Cyp46a1 enzyme and culminating into the conversion of cholesterol to 24(S)‐hydroxycholesterol. Increased 24(S)‐hydroxycholesterol concentration is toxic to neurons, propelling neuronal apoptosis through the Fas‐mediated extrinsic apoptosis pathway. For the first time, perturbation of cholesterol homeostasis in brain is shown to be utilized by the viruses for both maturation and the release of its matured virions outside the cells for continuous neuropathogenesis.

image

Chandipura virus (CHPV) increases cholesterol import through low density lipid (LDL) receptor in neurons. Cholesterol in neurons are utilized to form the CHPV envelope. Excessive accumulation of cholesterol gets converted to 24(S)‐hydroxycholesterol (24(S)‐OHC) by cholesterol 24‐hydroxylase enzyme (encoded by Cyp46a1 gene) that induces neuronal death through apoptosis. Therapeutics aimed against cholesterol homeostasis perturbation may be an effective anti‐viral strategy.
SorCS1 variants and amyloid precursor protein (APP) are co‐transported in neurons but only SorCS1c modulates anterograde APP transport
Authors: Hermey Guido , Schmidt Nadine , Bluhm Björn , Mensching Daniel , Ostermann Kristina , Rupp Carsten , Kuhl Dietmar , Kins Stefan
Published: June 2015

Processing of amyloid precursor protein (APP) into amyloid‐β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface‐bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co‐immunoprecipitation and co‐localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post‐endocytic pathway. We introduce functional Venus‐tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP‐positive transport vesicles contain SorCS1. Co‐expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP‐positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.

image

Altered APP trafficking is thought to modulate its processing. SorCS1 has been suggested to function in APP trafficking. We analyzed if the two SorCS1 variants, SorCS1b and SorCS1c, tie APP to the cell surface or modify its internalization and intracellular targeting. We observed co‐localization and vesicular co‐transport of APP and SorCS1, but independent internalization and sorting through a common post‐endocytic pathway. Co‐expression of one variant, SorCS1c, reduced anterograde APP transport. These data demonstrate that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.
Mu opioid receptor activation enhances regulator of G protein signaling 4 association with the mu opioid receptor/G protein complex in a GTP‐dependent manner
Authors: Santhappan Rema , Crowder Alicia Tamara , Gouty Shawn , Cox Brian M. , Côté Thomas E.
Published: June 2015

The interaction of Regulator of G protein Signaling 4 (RGS4) with the rat mu opioid receptor (MOR)/G protein complex was investigated. Solubilized MOR from rat brain membranes was immunoprecipitated in the presence of RGS4 with antibodies against the N‐terminus of MOR (anti‐MOR10–70). Activation of MOR with [D‐Ala2, N‐Me‐Phe4, Gly5‐ol] enkephalin (DAMGO) during immunoprecipitation caused a 150% increase in Goα and a 50% increase in RGS4 in the pellet. When 10 μM GTP was included with DAMGO, there was an additional 72% increase in RGS4 co‐immunoprecipitating with MOR (p = 0.003). Guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS) increased the amount of co‐precipitating RGS4 by 93% (compared to DAMGO alone, p = 0.008), and the inclusion of GTPγS caused the ratio of MOR to RGS4 to be 1 : 1 (31 fmoles : 28 fmoles, respectively). GTPγS also increased the association of endogenous RGS4 with MOR. In His6RGS4/Ni2+‐NTA agarose pull down experiments, 0.3 μM GTPγS tripled the binding of Goα to His6RGS4, whereas the addition of 100 μM GDP blocked this effect. Importantly, activation of solubilized MOR with DAMGO in the presence of 100 μM GDP and 0.3 μM GTPγS increased Goα binding to His6RGS4/Ni2+‐NTA agarose (p = 0.001).

image

Regulators of G protein Signaling (RGS) shorten the time that G proteins are active. Activation of the mu opioid receptor (MOR) causes GTP to bind to and to activate Go (αoβγ). RGS4 then binds to the activated αo‐GTP/MOR complex and accelerates the intrinsic GTPase of αo. After αo dissociates from MOR, RGS4 remains bound to the C‐terminal region of MOR.
Serum WFA+‐M2BP levels as a prognostic factor in patients with early hepatocellular carcinoma undergoing curative resection
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Kaneoka Yuji , Maeda Atsuyuki , Korenaga Masaaki , Mizokami Masashi , Narimatsu Hisashi
Published: July 2015

Background & Aims

Serum tumour markers for hepatocellular carcinoma (HCC) have less prognostic significance in early stage. Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA+‐M2BP) levels are reportedly associated with hepatocarcinogenic potential in patients with chronic liver diseases. We investigated the prognostic significance of pretreatment serum WFA+‐M2BP levels in patients with early‐stage HCC.

Methods

A total of 240 patients who underwent hepatic resection for naïve Barcelona Clinic Liver Cancer (BCLC) class 0 or A HCC were analysed. WFA+‐M2BP and tumour markers for HCC were measured from serum obtained just prior to treatment. Post‐operative recurrence and survival rates were compared according to these serum markers, tumour stage and Child–Pugh class.

Results

There was an association between serum WFA+‐M2BP levels and the fibrosis grade of resected noncancerous liver tissue, whereas no association was found between WFA+‐M2BP levels and tumour progression or liver function. In a multivariate analysis, pretreatment serum WFA+‐M2BP level was associated with recurrence and survival, respectively, independent of HCC progression or fibrosis grade of resected noncancerous liver tissue. Recurrence rates after hepatic resection were significantly higher in patients with a pretreatment serum WFA+‐M2BP ≥ 3.00 than those with a pretreatment serum WFA+‐M2BP < 3.00 (P = 0.0038). Survival rates were lower in patients with a pretreatment serum WFA+‐M2BP ≥ 3.00 than those with a pretreatment serum WFA+‐M2BP < 3.00 (P = 0.0187).

Conclusions

Serum WFA+‐M2BP level is a prognostic factor for recurrence and survival, in addition to tumour progression and liver function, in patients with early‐stage HCC treated with curative hepatic resection.
Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (Sarcophilus harrisii)
Authors: Morris Katrina M. , Wright Belinda , Grueber Catherine E. , Hogg Carolyn , Belov Katherine
Published: June 2015

The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction due to the spread of devil facial tumour disease. Polymorphisms in immune genes can provide adaptive potential to resist diseases. Previous studies in diversity at immune loci in wild species have almost exclusively focused on genes of the major histocompatibility complex (MHC); however, these genes only account for a fraction of immune gene diversity. Devils lack diversity at functionally important immunity loci, including MHC and Toll‐like receptor genes. Whether there are polymorphisms at devil immune genes outside these two families is unknown. Here, we identify polymorphisms in a wide range of key immune genes, and develop assays to type single nucleotide polymorphisms (SNPs) within a subset of these genes. A total of 167 immune genes were examined, including cytokines, chemokines and natural killer cell receptors. Using genome‐level data from ten devils, SNPs within coding regions, introns and 10 kb flanking genes of interest were identified. We found low polymorphism across 167 immune genes examined bioinformatically using whole‐genome data. From this data, we developed long amplicon assays to target nine genes. These amplicons were sequenced in 29–220 devils and found to contain 78 SNPs, including eight SNPS within exons. Despite the extreme paucity of genetic diversity within these genes, signatures of balancing selection were exhibited by one chemokine gene, suggesting that remaining diversity may hold adaptive potential. The low functional diversity may leave devils highly vulnerable to infectious disease, and therefore, monitoring and preserving remaining diversity will be critical for the long‐term management of this species. Examining genetic variation in diverse immune genes should be a priority for threatened wildlife species. This study can act as a model for broad‐scale immunogenetic diversity analysis in threatened species.
Immunogenetic heterogeneity in a widespread ungulate: the European roe deer (Capreolus capreolus)
Authors: Quéméré Erwan , Galan Maxime , Cosson Jean‐François , Klein François , Aulagnier Stéphane , Gilot‐Fromont Emmanuelle , Merlet Joël , Bonhomme Maxime , Hewison A. J. Mark , Charbonnel Nathalie
Published: June 2015

Understanding how immune genetic variation is shaped by selective and neutral processes in wild populations is of prime importance in both evolutionary biology and epidemiology. The European roe deer (Capreolus capreolus) has considerably expanded its distribution range these last decades, notably by colonizing agricultural landscapes. This range shift is likely to have led to bottlenecks and increased roe deer exposure to a new range of pathogens that until recently predominantly infected humans and domestic fauna. We therefore investigated the historical and contemporary forces that have shaped variability in a panel of genes involved in innate and acquired immunity in roe deer, including Mhc‐Drb and genes encoding cytokines or toll‐like receptors (TLRs). Together, our results suggest that genetic drift is the main contemporary evolutionary force shaping immunogenetic variation within populations. However, in contrast to the classical view, we found that some innate immune genes involved in micropathogen recognition (e.g. Tlrs) continue to evolve dynamically in roe deer in response to pathogen‐mediated positive selection. Most studied Tlrs (Tlr2, Tlr4 and Tlr5) had similarly high levels of amino acid diversity in the three studied populations including one recently established in southwestern France that showed a clear signature of genetic bottleneck. Tlr2 implicated in the recognition of Gram‐positive bacteria in domestic ungulates, showed strong evidence of balancing selection. The high immunogenetic variation revealed here implies that roe deer are able to cope with a wide spectrum of pathogens and to respond rapidly to emerging infectious diseases.
Constitutive presence of antibiotic resistance genes within the bacterial community of a large subalpine lake
Authors: Di Cesare Andrea , Eckert Ester M. , Teruggi Alessia , Fontaneto Diego , Bertoni Roberto , Callieri Cristiana , Corno Gianluca
Published: June 2015

The fate of antibiotic resistance genes (ARGs) in environmental microbial communities is of primary concern as prodromal of a potential transfer to pathogenic bacteria. Although of diverse origin, the persistence of ARGs in aquatic environments is highly influenced by anthropic activities, allowing potential control actions in well‐studied environments. However, knowledge of abundance and space–time distribution of ARGs in ecosystems is still scarce. Using quantitative real‐time PCR, we investigated the presence and the abundance of twelve ARGs (against tetracyclines, β‐lactams, aminoglycosides, quinolones and sulphonamides) at different sampling sites, depths and seasons, in Lake Maggiore, a large subalpine lake, and in the area of its watershed. We then evaluated the correlation between each ARG and a number of ecological parameters in the water column in the deepest part of the lake. Our results suggest the constitutive presence of at least four ARGs within the bacterial community with a high proportion of bacteria potentially resistant to tetracyclines and sulphonamides. The presence of these ARGs was independent of the total bacterial density and temperature. The dynamics of tet(A) and sulII genes were, however, positively correlated with dissolved oxygen and negatively to chlorophyll a, suggesting that the resistant microbes inhabit specific niches. These observations indicate that the lake is a reservoir of antibiotic resistances, highlighting the need of a deeper understanding of the sources of ARGs and the factors allowing their persistence in waters.
Transcriptome sequencing reveals both neutral and adaptive genome dynamics in a marine invader
Authors: Tepolt C. K. , Palumbi S. R.
Published: June 2015

Species invasions cause significant ecological and economic damage, and genetic information is important to understanding and managing invasive species. In the ocean, many invasive species have high dispersal and gene flow, lowering the discriminatory power of traditional genetic approaches. High‐throughput sequencing holds tremendous promise for increasing resolution and illuminating the relative contributions of selection and drift in marine invasion, but has not yet been used to compare the diversity and dynamics of a high‐dispersal invader in its native and invaded ranges. We test a transcriptome‐based approach in the European green crab (Carcinus maenas), a widespread invasive species with high gene flow and a well‐known invasion history, in two native and five invasive populations. A panel of 10 809 transcriptome‐derived nuclear SNPs identified significant population structure among highly bottlenecked invasive populations that were previously undifferentiated with traditional markers. Comparing the full data set and a subset of 9246 putatively neutral SNPs strongly suggested that non‐neutral processes are the primary driver of population structure within the species’ native range, while neutral processes appear to dominate in the invaded range. Non‐neutral native range structure coincides with significant differences in intraspecific thermal tolerance, suggesting temperature as a potential selective agent. These results underline the importance of adaptation in shaping intraspecific differences even in high geneflow marine invasive species. They also demonstrate that high‐throughput approaches have broad utility in determining neutral structure in recent invasions of such species. Together, neutral and non‐neutral data derived from high‐throughput approaches may increase the understanding of invasion dynamics in high‐dispersal species.
Shoot bending promotes flower bud formation by miRNA‐mediated regulation in apple (Malus domestica Borkh.)
Authors: Xing Libo , Zhang Dong , Zhao Caiping , Li Youmei , Ma Juanjuan , An Na , Han Mingyu
Published: July 2015

Flower induction in apple (Malus domestica Borkh.) trees plays an important life cycle role, but young trees produce fewer and inferior quality flower buds. Therefore, shoot bending has become an important cultural practice, significantly promoting the capacity to develop more flower buds during the growing seasons. Additionally, microRNAs (miRNAs) play essential roles in plant growth, flower induction and stress responses. In this study, we identified miRNAs potentially involved in the regulation of bud growth, and flower induction and development, as well as in the response to shoot bending. Of the 195 miRNAs identified, 137 were novel miRNAs. The miRNA expression profiles revealed that the expression levels of 68 and 27 known miRNAs were down‐regulated and up‐regulated, respectively, in response to shoot bending, and that the 31 differentially expressed novel miRNAs between them formed five major clusters. Additionally, a complex regulatory network associated with auxin, cytokinin, abscisic acid (ABA) and gibberellic acid (GA) plays important roles in cell division, bud growth and flower induction, in which related miRNAs and targets mediated regulation. Among them, miR396, 160, 393, and their targets associated with AUX, miR159, 319, 164, and their targets associated with ABA and GA, and flowering‐related miRNAs and genes, regulate bud growth and flower bud formation in response to shoot bending. Meanwhile, the flowering genes had significantly higher expression levels during shoot bending, suggesting that they are involved in this regulatory process. This study provides a framework for the future analysis of miRNAs associated with multiple hormones and their roles in the regulation of bud growth, and flower induction and formation in response to shoot bending in apple trees.
A Family of Potent Ru(II) Photosensitizers with Enhanced DNA Intercalation: Bimodal Photokillers
Authors: Pefkianakis Eleftherios K. , Theodossiou Theodossis A. , Toubanaki Dimitra K. , Karagouni Evdokia , Falaras Polycarpos , Papadopoulos Kyriakos , Vougioukalakis Georgios C.
Published: June 2015

A new family of Ru(II)‐based photosensitizers was synthesized and systematically characterized. The ligands employed to coordinate the ruthenium metal center were the commercially available 2,2′‐bipyridine and a pyridine‐quinoline hybrid bearing an anthracene moiety. The complexes obtained carry either or Cl− counterions. These counterions determine the complexes' hydrophobic or hydrophilic character, respectively, therefore dictating their solubility in biologically related media. All photosensitizers exhibit characteristic, relatively strong and wide UV–Vis absorption spectral profiles. Their high efficiency in generating cytotoxic singlet oxygen was established (up to ΦΔ ~0.8). Moreover, the interaction of these photosensitizers with double‐stranded DNA was studied fluoro‐ and photospectroscopically and their binding affinities were found to be of the order of 3 × 107 M−1. All complexes are photocytotoxic to DU145 human prostate cancer cells. The highest light‐induced toxicity was conferred by the photosensitizers bearing Cl− counterions, probably due to the looser ionic “chaperoning” of Cl−, in comparison to , leading to higher cell internalization.
Effect of 808 nm Diode Laser on Swimming Behavior, Food Vacuole Formation and Endogenous ATP Production of Paramecium primaurelia (Protozoa)
Authors: Amaroli Andrea , Ravera Silvia , Parker Steven , Panfoli Isabella , Benedicenti Alberico , Benedicenti Stefano
Published: June 2015

Photobiomodulation (PBM) has been used in clinical practice for more than 40 years. To clarify the mechanisms of action of PBM at cellular and organism levels, we investigated its effect on Paramecium primaurelia (Protozoa) irradiated by an 808 nm infrared diode laser with a flat‐top handpiece (1 W in CW). Our results led to the conclusion that: (1) the 808 nm laser stimulates the P. primaurelia without a thermal effect, (2) the laser effect is demonstrated by an increase in swimming speed and in food vacuole formation, (3) the laser treatment affects endogenous adenosine triphosphate (ATP) production in a positive way, (4) the effects of irradiation dose suggest an optimum exposure time of 50 s (64 J cm−2 of fluence) to stimulate the Paramecium cells; irradiation of 25 s shows no effect or only mild effects and irradiation up to 100 s does not increase the effect observed with 50 s of treatment, (5) the increment of endogenous ATP concentration highlights the positive photobiomodulating effect of the 808 nm laser and the optimal irradiation conditions by the flat‐top handpiece.
Therapeutic Ultrasound as a Potential Male Dog Contraceptive: Determination of the Most Effective Application Protocol
Authors: Leoci R , Aiudi G , Silvestre F , Lissner EA , Marino F , Lacalandra GM
Published: July 2015

Contents

Ultrasound is one of the most promising forms of non‐invasive contraception and has been studied in several animal models. The objective of the current investigation was to determine the most practical and effective application protocol for dog sterilization. A total of 100 dogs were divided into five equal groups. Group A received 5‐min applications three times performed at 48‐hr intervals and covering the entire testicular area at frequency of 1 MHz; Group B received 5‐min applications three times performed at 48‐hr intervals over the dorso‐cranial area of the testis at frequency of 3 MHz; Group C received three sequential 5‐min applications (at 5‐min intervals between applications) covering the entire testicular area at frequency of 1 MHz; Group D received 15‐min applications two times performed at 48‐hr intervals and covering the entire testicular area at frequency of 1 MHz. The experimental groups' ultrasound had an intensity of 1.5W/cm2. The Control Group had the same procedure as Group A, but with the transducer switched‐off. Dogs were surgically castrated 40 days following the treatment for histological examination. Azoospermia, testicular volume reduction and apparently irreversible testicular damage were achieved by Group A. No effects were noticed in the other groups. Testosterone levels remained within physiological range with all application protocols. A regimen of three applications of ultrasound at 1 MHz, and 1.5 W/cm2, lasting 5 min with an interval of 48 h was effective as permanent sterilization in the dog without hormonal impact.
New Insights and Biomarkers for Type 1 Diabetes: Review for Scandinavian Journal of Immunology
Authors: Heinonen M. T. , Moulder R. , Lahesmaa R.
Published: June 2015

The increasing incidence of type 1 diabetes observed in the past 60 years has spawned massive efforts in multiple research fields to elucidate the aetiology of this disease. While GWAS studies provide a good genetic basis for the current knowledge, it is clear that environmental triggers and their influence in disease prevalence and origin are highly important. The realization of disease heterogeneity has created a requirement for better biomarkers to complement the known autoantibody markers and to more successfully predict the severity and onset time of the disease. Such biomarkers would be needed both for prevention as well as for monitoring disease activity and response to preventive and therapeutic measures. Systematic holistic approaches concentrating on the triggering molecular mechanisms, pancreatic beta cells, immune response, as well as the influence of diet and environment, are necessary to understand the disease pathogenesis and find a cure. The current genomic knowledge is being broadened with accompanying studies in epigenetics and transcriptomic regulation, metabolomics, proteomics and lipidomics, covering the whole system from beta cells, the profile and cellular balance of the infiltrating lymphocytes, to gut microbiota and viral infections. Here we highlight interesting recent findings in type 1 diabetes research.