bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroclinical findings of minor motor events during sleep in temporal lobe epilepsy
Authors: Giuliano Loretta , Uccello Denise , Fatuzzo Daniela , Mainieri Greta , Zappia Mario , Sofia Vito
Published: May 2017

Objective

It is well known that sleep‐related motor seizures can originate from the temporal lobe. However, little is known about the clinical features of minor motor manifestations during sleep in patients with temporal lobe epilepsy. The main objective of our study was to verify the existence of minor motor events during sleep in patients with mesial temporal lobe epilepsy (MTLE) and to define their clinical features and electroencephalography (EEG) correlations.

Methods

We enrolled in the study patients with diagnosis of symptomatic MTLE and a group of healthy controls. All patients and controls underwent long‐term video ‐EEG monitoring, including at least one night of nocturnal sleep. We analyzed all the movements recorded during nocturnal sleep of patients and controls and their electroencephalographic correlations.

Results

We analyzed the nocturnal sleep of 15 patients with symptomatic MTLE (8 males and 7 females; mean age ± standard deviation [SD]31.8 ± 14.9 years) and of 15 healthy controls (6 males and 9 females; mean age ± SD 32.8 ± 11.2 years). The analysis of movements during sleep revealed significant differences between groups, with the patients presenting significantly more movements in sleep than healthy controls (56.7 ± 39.2 vs. 15 ± 6.1; p < 0.001) with significant differences regarding oroalimentary automatisms, limb dystonia, straightening movements and gestural automatisms. EEG analysis showed that the proportion of movements preceded by EEG abnormalities was significantly higher in patients than in controls (57.8 ± 35.9 movements vs. 16.6 ± 13.4 movements; p < 0.001).

Significance

The results of our study demonstrated the presence of minor motor events during sleep in patients with MTLE, suggesting an epileptic origin of these episodes. The study of nocturnal sleep in MTLE patients is useful in helping the clinicians in the diagnostic and therapeutic workup of these patients.
Structural and functional responses of leaf‐associated fungal communities to chemical pollution in streams
Authors: Rossi Florent , Artigas Joan , Mallet Clarisse
Published: May 2017

The decomposition of allochthonous plant litter is a key ecological process in forested streams, involving the lignolytic activities of aquatic fungi. In this study we investigated the relationship between water pollution (by a mixture of nutrients, metals and pesticides) and the biomass, structure and enzyme activities of leaf‐associated fungal communities.

The experiment was performed through a microcosm approach by comparing fungal communities from a less‐polluted upstream site to a more‐polluted downstream site in the agricultural basin of the Auzon stream (Puy‐de‐Dôme region, Centre France). The resistance as well as the ability of these fungal communities to recover from pollution was also assessed through a translocation experiment.

Results showed a lower laccase activity and higher band richness in fungal communities from the downstream site comparing to the upstream site, which can partially be explained by the greater pesticide toxicity and concentration of dissolved organic carbon of downstream waters.

Specifically, a negative relationship between laccase activity and nitrate concentration was observed, irrespectively of the studied site, whereas the relationship between nitrate and phenol oxidase/peroxidase appeared much weaker.

The translocation experiment evidenced (1) a fast decrease in laccase activity concomitant with a shift in fungal structure after stress exposure, and (2) a recovery ability in terms of laccase activity and fungal community structure 2 weeks after stress removal.

This study underlines the sensitivity of leaf‐associated fungal communities in terms of laccase activity and community structure to variations in chemical stress, as well as their ability to recover once the stress is removed. This study highlights the potential use of laccase as an indicator of chemical pollution of streams.
The impacts of overwintered green frog larvae on wood frog embryo mortality under a wetter climate
Authors: Crump Paul , Houlahan Jeff
Published: May 2017

For many species, the distribution and quantity of habitat is likely to be altered under climate change scenarios. Globally, temperatures are expected to increase, but changes in precipitation will be variable with some locations expected to receive more and other locations to receive less. The amount and timing of precipitation has a strong influence on wetland hydroperiod, which is a critical factor in determining wetland use by species of pond‐breeding amphibians. Past research has focused on the direct effects of reductions in precipitation and shorter hydroperiods, such as larvae desiccation, but little attention has been given to the indirect consequences of increased precipitation and longer hydroperiods, such as changes in predation pressure.

We used wood frogs (Lithobates sylvaticus), a species that typically breeds in ephemeral (temporary) wetlands, to test the hypothesis that increased precipitation and permanent wetlands would indirectly increase mortality in wood frog embryos through increases in the density of embryo predators, second‐year green frog larvae (Lithobates clamitans), limnephilid and phryganeid caddisfly larvae and red‐spotted newts (Notophthalmus viridescens). We conducted translocation experiments in 2014 and 2015. We monitored wood frog embryo hatch success and mortality from predation using open (predator access) and closed (predators excluded) cages in 16 wetlands in each year.

We observed no difference in embryo hatch success between ephemeral and permanent wetlands, with water temperature, not pH, affecting hatch rates. Wood frog embryos in permanent wetlands with overwintered second‐year green frog larvae had higher mortality from predation (0.80, 95% confidence intervals 0.65–0.91) than permanent wetlands (0.42, CI 0.26–0.60) and ephemeral wetlands (0.37, CI 0.31–0.45) that lacked predatory green frog larvae. Embryo mortality from predation increased with increasing green frog larvae density. Regression models showed that ponds with larvae densities >2.5 larvae m−2 resulted in 90% embryo mortality. Caddisfly larvae and red‐spotted newt density had no effect, and pond water temperature had a weak negative effect on embryo mortality from predation.

Under a wetter and warmer climate, springtime occupancy of predatory green frog larvae is likely to increase, resulting in a reduction in the amount of suitable wood frog breeding habitat. Our research suggests that indirect effects of climate change mediated through biotic interactions may play a critical role in the distribution of ephemeral wetland species.
Global evaluation of a semiempirical model for yield anomalies and application to within‐season yield forecasting
Authors: Schauberger Bernhard , Gornott Christoph , Wechsung Frank
Published: May 2017

Quantifying the influence of weather on yield variability is decisive for agricultural management under current and future climate anomalies. We extended an existing semiempirical modeling scheme that allows for such quantification. Yield anomalies, measured as interannual differences, were modeled for maize, soybeans, and wheat in the United States and 32 other main producer countries. We used two yield data sets, one derived from reported yields and the other from a global yield data set deduced from remote sensing. We assessed the capacity of the model to forecast yields within the growing season. In the United States, our model can explain at least two‐thirds (63%–81%) of observed yield anomalies. Its out‐of‐sample performance (34%–55%) suggests a robust yield projection capacity when applied to unknown weather. Out‐of‐sample performance is lower when using remote sensing‐derived yield data. The share of weather‐driven yield fluctuation varies spatially, and estimated coefficients agree with expectations. Globally, the explained variance in yield anomalies based on the remote sensing data set is similar to the United States (71%–84%). But the out‐of‐sample performance is lower (15%–42%). The performance discrepancy is likely due to shortcomings of the remote sensing yield data as it diminishes when using reported yield anomalies instead. Our model allows for robust forecasting of yields up to 2 months before harvest for several main producer countries. An additional experiment suggests moderate yield losses under mean warming, assuming no major changes in temperature extremes. We conclude that our model can detect weather influences on yield anomalies and project yields with unknown weather. It requires only monthly input data and has a low computational demand. Its within‐season yield forecasting capacity provides a basis for practical applications like local adaptation planning. Our study underlines high‐quality yield monitoring and statistics as critical prerequisites to guide adaptation under climate change.
Climate‐driven geographic distribution of the desert locust during recession periods: Subspecies’ niche differentiation and relative risks under scenarios of climate change
Authors: Meynard Christine N. , Gay Pierre‐Emmanuel , Lecoq Michel , Foucart Antoine , Piou Cyril , Chapuis Marie‐Pierre
Published: May 2017

The desert locust is an agricultural pest that is able to switch from a harmless solitarious stage, during recession periods, to swarms of gregarious individuals that disperse long distances and affect areas from western Africa to India during outbreak periods. Large outbreaks have been recorded through centuries, and the Food and Agriculture Organization keeps a long‐term, large‐scale monitoring survey database in the area. However, there is also a much less known subspecies that occupies a limited area in Southern Africa. We used large‐scale climatic and occurrence data of the solitarious phase of each subspecies during recession periods to understand whether both subspecies climatic niches differ from each other, what is the current potential geographical distribution of each subspecies, and how climate change is likely to shift their potential distribution with respect to current conditions. We evaluated whether subspecies are significantly specialized along available climate gradients by using null models of background climatic differences within and between southern and northern ranges and applying niche similarity and niche equivalency tests. The results point to climatic niche conservatism between the two clades. We complemented this analysis with species distribution modeling to characterize current solitarious distributions and forecast potential recession range shifts under two extreme climate change scenarios at the 2050 and 2090 time horizon. Projections suggest that, at a global scale, the northern clade could contract its solitarious recession range, while the southern clade is likely to expand its recession range. However, local expansions were also predicted in the northern clade, in particular in southern and northern margins of the current geographical distribution. In conclusion, monitoring and management practices should remain in place in northern Africa, while in Southern Africa the potential for the subspecies to pose a threat in the future should be investigated more closely.
Trade‐offs for food production, nature conservation and climate limit the terrestrial carbon dioxide removal potential
Authors: Boysen Lena R. , Lucht Wolfgang , Gerten Dieter
Published: May 2017

Large‐scale biomass plantations (BPs) are a common factor in climate mitigation scenarios as they promise double benefits: extracting carbon from the atmosphere and providing a renewable energy source. However, their terrestrial carbon dioxide removal (tCDR) potentials depend on important factors such as land availability, efficiency of capturing biomass‐derived carbon and the timing of operation. Land availability is restricted by the demands of future food production depending on yield increases and population growth, by requirements for nature conservation and, with respect to climate mitigation, avoiding unfavourable albedo changes. We integrate these factors in one spatially explicit biogeochemical simulation framework to explore the tCDR opportunity space on land available after these constraints are taken into account, starting either in 2020 or 2050, and lasting until 2100. We find that assumed future needs for nature protection and food production strongly limit tCDR potentials. BPs on abandoned crop and pasture areas (~1,300 Mha in scenarios of either 8.0 billion people and yield gap reductions of 25% until 2020 or 9.5 billion people and yield gap reductions of 50% until 2050) could, theoretically, sequester ~100 GtC in land carbon stocks and biomass harvest by 2100. However, this potential would be ~80% lower if only cropland was available or ~50% lower if albedo decreases were considered as a factor restricting land availability. Converting instead natural forest, shrubland or grassland into BPs could result in much larger tCDR potentials ̶ but at high environmental costs (e.g. biodiversity loss). The most promising avenue for effective tCDR seems to be improvement of efficient carbon utilization pathways, changes in dietary trends or the restoration of marginal lands for the implementation of tCDR.
Shifting Pacific storm tracks as stressors to ecosystems of western North America
Authors: Dannenberg Matthew P. , Wise Erika K.
Published: May 2017

Much of the precipitation delivered to western North America arrives during the cool season via midlatitude Pacific storm tracks, which may experience future shifts in response to climate change. Here, we assess the sensitivity of the hydroclimate and ecosystems of western North America to the latitudinal position of cool‐season Pacific storm tracks. We calculated correlations between storm track variability and three hydroclimatic variables: gridded cool‐season standardized precipitation‐evapotranspiration index, April snow water equivalent, and water year streamflow from a network of USGS stream gauges. To assess how historical storm track variability affected ecosystem processes, we derived forest growth estimates from a large network of tree‐ring widths and land surface phenology and wildfire estimates from remote sensing. From 1980 to 2014, cool‐season storm tracks entered western North America between approximately 41°N and 53°N. Cool‐season moisture supply and snowpack responded strongly to storm track position, with positive correlations to storm track latitude in eastern Alaska and northwestern Canada but negative correlations in the northwestern U.S. Ecosystems of the western United States were greener and more productive following winters with south‐shifted storm tracks, while Canadian ecosystems were greener in years when the cool‐season storm track was shifted to the north. On average, larger areas of the northwestern United States were burned by moderate to high severity wildfires when storm tracks were displaced north, and the average burn area per fire also tended to be higher in years with north‐shifted storm tracks. These results suggest that projected shifts of Pacific storm tracks over the 21st century would likely alter hydroclimatic and ecological regimes in western North America, particularly in the northwestern United States, where moisture supply and ecosystem processes are highly sensitive to the position of cool‐season storm tracks.
Estimating Groundwater Mounding in Sloping Aquifers for Managed Aquifer Recharge
Authors: Zlotnik Vitaly A. , Kacimov Anvar , Al‐Maktoumi Ali
Published: May 2017

Design of managed aquifer recharge (MAR) for augmentation of groundwater resources often lacks detailed data, and simple diagnostic tools for evaluation of the water table in a broad range of parameters are needed. In many large‐scale MAR projects, the effect of a regional aquifer base dip cannot be ignored due to the scale of recharge sources (e.g., wadis, streams, reservoirs). However, Hantush's (1967) solution for a horizontal aquifer base is commonly used. To address sloping aquifers, a new closed‐form analytical solution for water table mound accounts for the geometry and orientation of recharge sources at the land surface with respect to the aquifer base dip. The solution, based on the Dupiuit‐Forchheimer approximation, Green's function method, and coordinate transformations is convenient for computing. This solution reveals important MAR traits in variance with Hantush's solution: mounding is limited in time and space; elevation of the mound is strongly affected by the dip angle; and the peak of the mound moves over time. These findings have important practical implications for assessment of various MAR scenarios, including waterlogging potential and determining proper rates of recharge. Computations are illustrated for several characteristic MAR settings.
Optimization strategies aimed to increase the efficacy of H. pylori eradication therapies
Authors: Gisbert Javier P. , McNicholl Adrian G.
Published: May 2017

Background

As with any other infectious disease, we should aim for treatments offering ≥90% Helicobacter pylori eradication rates in clinical practice.

Aim

To summarize optimization strategies aimed to increase the efficacy of H. pylori eradication therapies.

Methods

A systematic bibliographic search (in PubMed up to August 2016) was designed to identify studies investigating optimization strategies aimed to increase the efficacy of H. pylori eradication therapies.

Results

The most direct way to optimize a treatment is using higher doses of drugs unless it has been shown that lower doses are equally effective. Similarly, prescriptions should use 14‐day duration unless a shorter scheme has been shown locally to be equally effective. Double‐dose proton‐pump inhibitor therapy is recommended for triple therapy and may probably increase the efficacy of nonbismuth concomitant regimen as well. The efficacy of triple therapies in the presence of resistance can be significantly improved by the addition of bismuth salts, which offer an additive effect in combination with antibiotics. Overall, probiotics seem to reduce antibiotic side effects, but the increase in eradication rates is not so evident; therefore, they cannot be generally recommended for clinical practice yet.

Conclusions

Using potent acid inhibition and/or higher antibiotic doses—especially by increasing the number of daily intakes—and lengthening treatments up to 14 days improves efficacy in most regimens and should be generally recommended. Triple therapies can be efficiently improved by the addition of bismuth salts, turning them into quadruple therapies. Finally, some treatments will require a combination of optimization strategies to significantly improve results.
Examination of PHOX2B in adult neuroendocrine neoplasms reveals relatively frequent expression in phaeochromocytomas and paragangliomas
Authors: Lee John P , Hung Yin P , O'Dorisio Thomas M , Howe James R , Hornick Jason L , Bellizzi Andrew M
Published: May 2017

Aims

Paired‐like homeobox 2b (PHOX2B) is a transcription factor with expression outside of the central nervous system restricted to neurons and chromaffin cells of the autonomic nervous system. Germline mutations cause congenital central hypoventilation syndrome and predispose to neuroblastoma and Hirschsprung disease. Among paediatric small round cell tumours, PHOX2B is neuroblastoma‐specific. Two studies of adult autonomic nervous system tumours (n = 62) produced conflicting results (all tumours stained in one; expression restricted to 40% of paragangliomas in the other). We examined PHOX2B expression in a large cohort of phaeochromocytomas and paragangliomas, as well as well‐differentiated neuroendocrine tumours (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs).

Methods and results

Tissue microarrays (TMAs) were constructed from 609 tumours: 111 phaeochromocytomas, 146 paragangliomas, 250 WDNETs, and 102 PDNECs. PHOX2B immunohistochemistry was scored for extent (%) and intensity (0–3+), and an H‐score (extent × intensity) was calculated. PHOX2B expression was seen in 32% of phaeochromocytomas and in 47% of paragangliomas. Mean/median H‐scores for these tumours were in the 30–55 range (i.e. weak to moderate staining). No WDNETs and only 7% of PDNECs stained, the latter often strongly. In a representative cohort of corresponding whole sections (n = 55), the results in WDNETs and PDNECs were unchanged, whereas half of the phaeochromocytomas/paragangliomas that were negative on TMAs became focally, weakly positive.

Conclusions

We found frequent, weak to moderate PHOX2B expression in phaeochromocytomas/paragangliomas and no expression in WDNETs, which could be diagnostically useful in the distinction of these tumours. Expression in a minority of PDNECs probably reflects the transcription factor lineage infidelity that is characteristic of this tumour class.
HMGA2 is a specific immunohistochemical marker for pleomorphic adenoma and carcinoma ex‐pleomorphic adenoma
Authors: Mito Jeffrey K , Jo Vickie Y , Chiosea Simion I , Dal Cin Paola , Krane Jeffrey F
Published: May 2017

Aims

Accurate classification of salivary gland neoplasms may be challenging, owing to morphological overlap, particularly in small biopsies. Recurrent translocations involving the high‐mobility group AT‐hook 2 (HMGA2) gene are present in a subset of pleomorphic adenomas (PAs) and carcinoma ex‐pleomorphic adenomas (CA ex‐PAs). The aim of this study was to evaluate immunohistochemical HMGA2 expression in 225 salivary gland tumours, including 56 PAs, 37 CA ex‐PAs, and 132 potential histological mimics, to determine its diagnostic utility.

Methods and results

HMGA2 expression was identified in 19 PAs (33.9%) and nine CA ex‐PAs (24.3%). Expression was strong and diffuse throughout all PAs, and in four of nine positive CA ex‐PAs. In five CA ex‐PAs, HMGA2 showed weak‐to‐strong multifocal staining within the carcinomatous component, and strong diffuse HMGA2 expression in the residual PA. Among histological mimics, six de‐novo salivary duct carcinomas (28.5%), three epithelial–myoepithelial carcinomas (33.3%) and one case each of myoepithelioma and basal cell adenoma expressed HMGA2. Fluorescence in‐situ hybridization for HMGA2 rearrangement performed on a subset of tumours that showed diffuse HMGA2 expression in PAs and CA ex‐PAs was frequently associated with rearrangement of the HMGA2 locus, whereas cases of de‐novo salivary duct carcinoma, or CA ex‐PA with limited or no HMGA2 expression, had an intact HMGA2 locus.

Conclusions

HMGA2 expression is a highly specific (96.2%), but low‐sensitivity (29.8%), marker for PA and CA ex‐PA when compared with histological mimics, and is frequently associated with rearrangement of the HMGA2 locus.
Elimination of GPR146‐mediated antiviral function through IRF3/HES1‐signalling pathway
Authors: Huang Hongjun , Zhang Na , Xiong Qingqing , Chen Ruoyu , Zhang Chengfei , Wang Ning , Wang Li , Ren Hua , Liu Mingyao , Qian Min , Du Bing
Published: May 2017

As the most important host defence against viral infection, interferon (IFN) stimulates hundreds of antiviral genes (ISGs) that together establish an ‘antiviral state’. However, the antiviral function of most ISGs in viral infection still need further exploration. Here, we demonstrated that the expression of G‐protein‐coupled receptor 146 (GPR146) is highly increased by both IFN‐β and IFN‐γ in a signal transducer and activator of transcription 1‐dependent signalling pathway. Most importantly, overexpression of GPR146 protects the host cells from vesicular stomatitis virus and Newcastle disease virus infection but not from infection by herpes simplex virus. In contrast, the virus‐induced IFN‐β production changed little in Gpr146‐knockout cells. Furthermore, the Gpr146‐deficient mice showed similar susceptibility to wild‐type mice with vesicular stomatitis virus infection. Interestingly, the expression of GPR146 in virus‐infected cells was strikingly reduced and can partially explain why the viral infection was little influenced in Gpr146‐knockout mice. Surprisingly, virus‐activated IFN regulatory factor 3 (IRF3) signalling not only induces the expression of IFN but also represses GPR146 expression through HES1 (hairy and enhancer of split‐1)‐mediated transcriptional activity to establish a dynamic equilibrium between pro‐viral and antiviral stages in host cells. Taken together, these data reveal the antiviral role of GPR146 in fighting viral infection although the GPR146‐mediated protection is eliminated by IRF3/HES1‐signalling, which suggests a potential therapeutic significance of both GPR146 and HES1 signalling in viral infection.
Cell death and thymic tolerance
Authors: Daley Stephen R. , Teh Charis , Hu Daniel Y. , Strasser Andreas , Gray Daniel H.D.
Published: May 2017

The differentiation of hematopoietic precursors into the many functionally distinct T‐cell types produced by the thymus is a complex process. It proceeds through a series of stages orchestrated by a variety of thymic microenvironments that shape the T‐cell developmental processes. Numerous cytokine and cell surface receptors direct thymocyte differentiation but the primary determinant of cell fate is the engagement of the T‐cell antigen receptor (TCR). The strength of the TCR signal and the maturation stage of the thymocyte receiving it can direct the various differentiation programs or, alternatively, end the process by inducing cell death. The regulation of thymocyte death is critical for the efficiency of thymic T‐cell differentiation and the preservation of immune tolerance. A detailed knowledge of mechanisms that eliminate thymocytes from the T‐cell repertoire is essential to understand the “logic” of T‐cell selection in the thymus. This review focuses on the central role of the BCL‐2 family of proteins in the apoptotic checkpoints that punctuate thymocyte differentiation and the consequences of defects in these processes.
Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases
Authors: Man Si Ming , Karki Rajendra , Kanneganti Thirumala‐Devi
Published: May 2017

Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase‐1, human caspase‐4 and caspase‐5, or mouse caspase‐11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore‐forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro‐inflammatory cytokines IL‐1β and IL‐18, alarmins and endogenous danger‐associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens.
Restimulation‐induced cell death: new medical and research perspectives
Authors: Zheng Lixin , Li Jian , Lenardo Michael
Published: May 2017

In the periphery, homeostasis of the immune system depends on the equilibrium of expanding and contracting T lymphocytes during immune response. An important mechanism of lymphocyte contraction is clonal depletion of activated T cells by cytokine withdrawal induced death (CWID) and TCR restimulation induced cell death (RICD). Deficiencies in signaling components for CWID and RICD leads to autoimmunune lymphoproliferative disorders in mouse and human. The most important feature of CWID and RICD is clonal specificity, which lends great appeal as a strategy for targeted tolerance induction and treatment of autoimmune diseases, allergic disorders, and graft rejection by depleting undesired disease‐causing T cells while keeping the overall host immunity intact.
RIPK3 in cell death and inflammation: the good, the bad, and the ugly
Authors: Orozco Susana , Oberst Andrew
Published: May 2017

Necroptosis is a form of cell death that can be observed downstream of death receptor or pattern recognition receptor signaling under certain cellular contexts, or in response to some viral and bacterial infections. The receptor interacting protein kinases‐1 (RIPK1) and RIPK3 are at the core of necroptotic signaling, among other proteins. Because this pathway is normally halted by the pro‐apoptotic protease caspase‐8 and the IAP ubiquitin ligases, how and when necroptosis is triggered in physiological settings are ongoing questions. Interestingly, accumulating evidence suggests that RIPK3 has functions beyond the induction of necroptotic cell death, especially in the areas of tissue injury and sterile inflammation. Here, we will discuss the role of RIPK3 in a variety of physiological conditions, including necroptotic and non‐necroptotic cell death, in the context of viral and bacterial infections, tissue damage, and inflammation.
Dying to protect: cell death and the control of T‐cell homeostasis
Authors: Li Kun‐Po , Shanmuganad Sharmila , Carroll Kaitlin , Katz Jonathan D. , Jordan Michael B. , Hildeman David A.
Published: May 2017

T cells play a critical role in immune responses as they specifically recognize peptide/MHC complexes with their T‐cell receptors and initiate adaptive immune responses. While T cells are critical for performing appropriate effector functions and maintaining immune memory, they also can cause autoimmunity or neoplasia if misdirected or dysregulated. Thus, T cells must be tightly regulated from their development onward. Maintenance of appropriate T‐cell homeostasis is essential to promote protective immunity and limit autoimmunity and neoplasia. This review will focus on the role of cell death in maintenance of T‐cell homeostasis and outline novel therapeutic strategies tailored to manipulate cell death to limit T‐cell survival (eg, autoimmunity and transplantation) or enhance T‐cell survival (eg, vaccination and immune deficiency).
Caspase‐8: regulating life and death
Authors: Tummers Bart , Green Douglas R.
Published: May 2017

Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best‐known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis. Of the two best understood pathways of apoptosis, the extrinsic and intrinsic (mitochondrial) pathways, the former is induced by the ligation of death receptors, a subset of the TNF receptor (TNFR) superfamily. Ligation of these death receptors can also induce necroptosis. The extrinsic apoptosis and necroptosis pathways regulate each other and their balance determines whether cells live. Integral in the regulation and initiation of death receptor‐mediated activation of programmed cell death is the aspartate‐specific cysteine protease (caspase)‐8. This review describes the role of caspase‐8 in the initiation of extrinsic apoptosis execution and the mechanism by which caspase‐8 inhibits necroptosis. The importance of caspase‐8 in the development and homeostasis and the way that dysfunctional caspase‐8 may contribute to the development of malignancies in mice and humans are also explored.
Augmentation programme for the endangered Ozark hellbender Cryptobranchus alleganiensis bishopi in Missouri
Authors: Ettling J. A. , Wanner M. D. , Pedigo A. S. , Kenkel J. L. , Noble K. R. , Briggler J. T.
Published: May 2017

The Ozark hellbender Cryptobranchus alleganiensis bishopi is an endangered aquatic salamander that inhabits cold‐water streams in the Ozark Highlands of Missouri and Arkansas in the USA. As a result of the drastic population declines over the past 40+ years, with a prominent shift in age structure (large, mature individuals predominate; young classes virtually absent), the Ozark Hellbender Working Group (OHWG) was established in 2001 to develop a conservation strategy for the species. The OHWG comprises representatives from state and federal agencies, Saint Louis Zoo (MO, USA), universities and interested individuals. Based on data from the Hellbender Population and Viability Assessment it was determined that without intervention, including a captive‐propagation, head‐start and augmentation programme, it was highly likely (>96% probability) that the species would go extinct within the next 75 years. Inter‐agency collaboration has facilitated significant progress since the inception of the captive‐propagation programme in 2002. The joint strategy of the world's first captive breeding of Ozark hellbenders in 2011 and subsequent captive breeding in the 2012–2015 period, together with the hatching and rearing of wild‐collected eggs, means 6737 larvae/juveniles have been produced and/or reared at the Saint Louis Zoo. Since 2008, 3138 juvenile Ozark hellbenders reared at Saint Louis Zoo have been released into the wild in Missouri to augment remaining populations in four different streams (Bryant Creek, North Fork of the White River, Current River and Eleven Point River). Based on the success of the captive‐propagation programme, post‐release survival and dedicated individuals of various organizations the future of the Ozark hellbender is looking optimistic.
Physical performances of alkali‐activated portland cement‐glass‐limestone blends
Authors: Thomsen René Mossing , Garzón Sergio Ferreiro , Herfort Duncan , Skibsted Jørgen , Yue Yuanzheng
Published: May 2017

The potential of calcium aluminosilicate (CAS) glasses as supplementary cementitious materials is studied in terms of the development of compressive strength for mortars containing a mixture of portland cement, CAS glass, and limestone. In addition, the impact of internal and external alkali activation of the cementitious systems on the mortar performances is investigated. Internal alkali activation is obtained by adding alkali oxides to the CAS glass system, whereas external alkali activation is realized by hydration of the blended cements containing alkali‐free CAS glasses using alkaline solutions. For the internally alkali‐activated systems and the alkali‐free mortars, higher strengths are achieved in comparison to the reference mortar prepared from plain ordinary portland cement. In contrast, the externally alkali‐activated mortars exhibit lower compressive strengths, implying the importance of both the immediate availability of alkali ions in the cementitious system and the increased dissolution rate of the glass particles caused by the network depolymerization. The glasses are also studied by thermal analysis and the results are used to calculate the theoretical CO2 emissions. The lowest embodied CO2 emission is estimated for the blends containing alkali‐activated CAS glasses.
Selection of core animals in the Algorithm for Proven and Young using a simulation model
Authors: Bradford H.L. , Pocrnić I. , Fragomeni B.O. , Lourenco D.A.L. , Misztal I.
Published: May 2017

The Algorithm for Proven and Young (APY) enables the implementation of single‐step genomic BLUP (ssGBLUP) in large, genotyped populations by separating genotyped animals into core and non‐core subsets and creating a computationally efficient inverse for the genomic relationship matrix (G). As APY became the choice for large‐scale genomic evaluations in BLUP‐based methods, a common question is how to choose the animals in the core subset. We compared several core definitions to answer this question. Simulations comprised a moderately heritable trait for 95,010 animals and 50,000 genotypes for animals across five generations. Genotypes consisted of 25,500 SNP distributed across 15 chromosomes. Genotyping errors and missing pedigree were also mimicked. Core animals were defined based on individual generations, equal representation across generations, and at random. For a sufficiently large core size, core definitions had the same accuracies and biases, even if the core animals had imperfect genotypes. When genotyped animals had unknown parents, accuracy and bias were significantly better (p ≤ .05) for random and across generation core definitions.
Geno‐Diver: A combined coalescence and forward‐in‐time simulator for populations undergoing selection for complex traits
Authors: Howard J. T. , Tiezzi F. , Pryce J. E. , Maltecca C.
Published: May 2017

Geno‐Diver is a combined coalescence and forward‐in‐time simulator designed to simulate complex traits with a quantitative and/or fitness component and implement multiple selection and mating strategies utilizing pedigree or genomic information. The simulation is carried out in two steps. The first step generates whole‐genome sequence data for founder individuals. A variety of trait architectures can be generated for quantitative and fitness traits along with their covariance. The second step generates new individuals forward‐in‐time based on a variety of selection and mating scenarios. Genetic values are predicted for individuals utilizing pedigree or genomic information. Relationship matrices and their associated inverses are generated using computationally efficient routines. We benchmarked Geno‐Diver with a previous simulation program and described how to simulate a traditional quantitative trait along with a quantitative and fitness trait. A user manual with examples, source code in C++11 and executable versions of Geno‐Diver for Linux are freely available at https://github.com/jeremyhoward/Geno-Diver.
Is it possible to enhance the confidence of student dietitians prior to professional placements? A design‐based research model
Authors: Ross L. J. , Mitchell L. J. , Williams L. T.
Published: May 2017

Background

Student confidence is an important contributor to a successful professional placement experience. The present study aimed to evaluate a placement preparation program for student dietitians and to assess the impact on self‐rated confidence with respect to commencing placements.

Methods

The present study is part of a design‐based research approach that involves students in a cyclic enquiry to evaluate and improve curricula. Nutrition and Dietetics students at an Australian university participated in a 1‐week mandatory workshop – Pre‐Placement week (PrePW), N = 98 students: in 2015 (n = 54) and 2016 (n = 44). An online survey was conducted before and after PrePW using a five‐point Likert scale (1 = not confident; 5 = very confident) to assess self‐rated confidence to commence placements. Mean (SD) scores were calculated. Paired and independent t‐tests evaluated within‐ and between‐group differences, respectively.

Results

Before PrePW, the mean (SD) for student confidence to commence placements overall (in all areas of practise) was ‘somewhat confident’ [2.9 (0.6) in 2015 and 3.0 (0.7) in 2016]. Students were least confident to commence Clinical Practice [2015: 2.5 (0.6); 2016: 2.8 (0.6)] compared to Food Service Management (FSM) [2015: 3.2 (0.9); 2016: 3.1 (0.9)] and Community and Public Health Nutrition (CPHN) [2015: 3.3 (0.9); 2016: 3.2 (0.8)]. Student feedback from PrePW 2015 was used to change the curriculum and PrePW program. The 2016 students reported significantly greater confidence within all areas of practice: Clinical Practice [3.4 (0.6)], FSM [3.7 (0.6)] and CPHN [3.8 (0.6)], including confidence to commence placements overall [3.6 (0.6)] (P < 0.05).

Conclusions

Design‐based research provides a useful framework for improvement to curricula and, in this case, was successful in enhancing student confidence in preparation for professional placement.
Expression of Concern: The haptoglobin beta subunit sequesters HMGB1 toxicity in sterile and infectious inflammation
Authors: Yang H. , Wang H. , Wang Y. , Addorisio M. , Li J. , Postiglione M. J. , Chavan S. S. , Al‐Abed Y. , Antoine D. J. , Andersson U. , Tracey K. J.
Published: May 2017

Background

Extra‐corpuscular haemoglobin is an endogenous factor enhancing inflammatory tissue damage, a process counteracted by the haemoglobin‐binding plasma protein haptoglobin composed of alpha and beta subunits connected by disulfide bridges. Recent studies established that haptoglobin also binds and sequesters another pro‐inflammatory mediator, HMGB1, via triggering CD163 receptor‐mediated anti‐inflammatory responses involving heme oxygenase‐1 expression and IL‐10 release. The molecular mechanism underlying haptoglobin–HMGB1 interaction remains poorly elucidated.

Methods

Haptoglobin β subunits were tested for HMGB1‐binding properties, as well as efficacy in animal models of sterile liver injury (induced by intraperitoneal acetaminophen administration) or infectious peritonitis (induced by cecal ligation and puncture, CLP, surgery) using wild‐type (C57BL/6) or haptoglobin gene‐deficient mice.

Results

Structural–functional analysis demonstrated that the haptoglobin β subunit recapitulates the HMGB1‐binding properties of full‐length haptoglobin. Similar to HMGB1–haptoglobin complexes, the HMGB1–haptoglobin β complexes also elicited anti‐inflammatory effects via CD163‐mediated IL‐10 release and heme oxygenase‐1 expression. Treatment with haptoglobin β protein conferred significant protection in mouse models of polymicrobial sepsis as well as acetaminophen‐induced liver injury, two HMGB1‐dependent inflammatory conditions.

Conclusions

Haptoglobin β protein offers a novel therapeutic approach to fight against various inflammatory diseases caused by excessive HMGB1 release.
Employee Insolvency Priorities and Employment Protection in France, Germany, and the United Kingdom
Authors: Mucciarelli Federico M.
Published: May 2017

When an employer becomes insolvent, employees’ claims for unpaid wages and contributions may be protected through statutory priorities, social security schemes, or a combination of both. This article compares the interplay of employee statutory priorities, if they exist, and social security schemes in France, Germany, and the United Kingdom. While France protects employees through both a statutory priority and a social security scheme, Germany and the United Kingdom have progressively reduced employment protection over the last forty years. Theories of varieties of capitalism and of legal origins cannot fully describe and explain the development of employment protection strategies in these countries. The evolution of the German and British regimes, in particular, are better explained as a sign of profound cultural shifts regarding the position of labour within firms and vis‐à‐vis other stakeholders. Finally, I also show that a cumulative application of employee priorities and insurance schemes is not necessarily redundant.
A Review of Implementation Outcome Measures of School‐Based Physical Activity Interventions
Authors: Shah Sonam , Allison Kenneth R. , Schoueri‐Mychasiw Nour , Pach Beata , Manson Heather , Vu‐Nguyen Karen
Published: May 2017

BACKGROUND

Measuring the implementation of school‐based physical activity (PA) interventions is an important prerequisite in assessing their impact. Prior to conducting a study to assess the implementation of the daily physical activity (DPA) policy in Ontario, Canada, a literature review was conducted to identify existing survey instruments to measure 5 implementation outcomes: adoption, fidelity, implementation cost, reach, and sustainability.

METHODS

A search for survey instruments to assess these implementation outcomes at the teacher and school administrator levels was conducted in 7 bibliographic databases, as well as the gray literature. Each survey instrument was coded as assessing 1 of the 5 implementation outcomes if it included at least 1 item measuring the construct.

RESULTS

Twenty‐three survey instruments were identified. None of the instruments were specifically developed to measure the implementation outcomes. Fidelity was the most common implementation outcome measured, followed by adoption. The least common implementation outcome measured was sustainability. Thirty‐five percent of survey instruments assessed were previously tested for validity and 26% were previously tested for reliability.

CONCLUSIONS

Based on this review, a gap in available instruments to measure implementation outcomes of school‐based PA programs was identified. An adapted theoretical framework, presented here, has potential application in future implementation studies.
Self-assembly hydrogels as multifunctional drug delivery of paclitaxel for synergistic tumour-targeting and biocompatibility in vitro and in vivo
Authors: Shu Chang , Sabi-mouka Eboka M B , Wang Xiaoliang , Ding Li
Published: May 2017

Objectives

In this work, we designed the self-assembly peptide hydrogels to multiply therapeutic agents for improving anticancer effect and lowering adverse reaction of paclitaxel (PTX).

Methods

The folate (FA)-peptide-PTX hydrogels consist of self-assemble peptide hydrogel as nanoscale carrier, FA and RGD peptide as targeting moieties and paclitaxel as anticancer drug. The properties of hydrogels, such as morphology, size distribution, zeta potential and rheology, were investigated. Targeted specificity, biodistribution and anticancer effect were studied both in vitro and in vivo.

Key findings

Folate-peptide-PTX hydrogel nanoparticles were spherical in shape with hydrodynamic diameter of approximately 137.3 ± 15.2 nm. The hydrogels could only target monolayer cancer cells but also penetrated the nuclei of cells in vitro. The in-vivo real-time imaging further demonstrated that the hydrogels preferentially accumulated in tumour and sustained release. Compared to free paclitaxel, the FA-peptide-PTX hydrogels had higher anticancer effect and lower side effect.

Conclusions

The dual-targeted drug delivery possessed strong capability of synergistic targeted delivery, long-term drug release and better biocompatibility than paclitaxel both in vitro and in vivo. The results obtained demonstrated a high potential of the proposed drug delivery system in improving the therapeutic efficacy of paclitaxel.
Evaluation of three popular diets fed to pet sugar gliders (Petaurus breviceps): Intake, digestion and nutrient balance
Authors: Dierenfeld E. S. , Whitehouse‐Tedd K. M.
Published: May 2017

Three diets fed to 12 pair‐housed sugar gliders, Petaurus breviceps, were evaluated through 5‐day intake and digestion trials following 10‐day transitions. Diets 1 and 2 comprised liquid formula mixes with added vegetables and fruit, and Diet 3 comprised extruded pellets and a liquid formula. Diets eaten contained 16 —19% crude protein, 3%–15% crude fat, 10%–11% neutral detergent fibre, 4%–20% starch and 8%–49% sugar (dry basis). Calculated individual dry matter intakes (DMI) ranged from 3.9 to 5.1 g/day, representing 58.2–78.4 kJ/day. DMI was greater for Diet 2 (7.2% BW) vs. Diet 1 (5.6; p = .006) and Diet 3 (4.2% BW; p = .003). Although these differences were no longer detectable on a MBW basis, animals were shown to have gained BW (+14.2 g; p = .03) on Diet 2. In addition to nutrient composition differing widely among diets, DM digestibility (DMD) was higher in Diet 1 (91.2%) compared to Diet 2 (87.3%; p = .03), but DMD for Diet 3 (88.9%) did not differ from other diets. Gliders demonstrated ability to digest a variety of energy substrates, including simple sugars (96%–99%), fats (81%–96%) and starches (79%–98%), as well as substantial insoluble dietary fibre (58%–75%), with significant difference among diets demonstrated for some nutrients. Animals displayed selective feeding behaviours, rejecting insoluble fibre in produce and preferring the lipid‐coated exterior of pellets. The diets used appeared to be balanced with respect to energy, protein and macromineral content, but may predispose to iron excess, other mineral imbalances (especially Ca deficiency) and obesity—clinical health issues described for pet gliders. Future focus on concentrations, types and utilization of dietary fibre in natural and captive diets, vitamin D metabolism and trace mineral interactions in sugar gliders would assist diet optimization for this highly gummivorous species.