bluuebunny/crossref_metadata_2025 huggingface dataset:
Both life‐history plasticity and local adaptation will shape range‐wide responses to climate warming in the tundra plant Silene acaulis
Authors: DeMarche Megan L. , Doak Daniel F. , Morris William F.
Published: November 2017

Many predictions of how climate change will impact biodiversity have focused on range shifts using species‐wide climate tolerances, an approach that ignores the demographic mechanisms that enable species to attain broad geographic distributions. But these mechanisms matter, as responses to climate change could fundamentally differ depending on the contributions of life‐history plasticity vs. local adaptation to species‐wide climate tolerances. In particular, if local adaptation to climate is strong, populations across a species’ range—not only those at the trailing range edge—could decline sharply with global climate change. Indeed, faster rates of climate change in many high latitude regions could combine with local adaptation to generate sharper declines well away from trailing edges. Combining 15 years of demographic data from field populations across North America with growth chamber warming experiments, we show that growth and survival in a widespread tundra plant show compensatory responses to warming throughout the species’ latitudinal range, buffering overall performance across a range of temperatures. However, populations also differ in their temperature responses, consistent with adaptation to local climate, especially growing season temperature. In particular, warming begins to negatively impact plant growth at cooler temperatures for plants from colder, northern populations than for those from warmer, southern populations, both in the field and in growth chambers. Furthermore, the individuals and maternal families with the fastest growth also have the lowest water use efficiency at all temperatures, suggesting that a trade‐off between growth and water use efficiency could further constrain responses to forecasted warming and drying. Taken together, these results suggest that populations throughout species’ ranges could be at risk of decline with continued climate change, and that the focus on trailing edge populations risks overlooking the largest potential impacts of climate change on species’ abundance and distribution.
Multifarious anchovy and sardine regimes in the Humboldt Current System during the last 150 years
Authors: Salvatteci Renato , Field David , Gutiérrez Dimitri , Baumgartner Tim , Ferreira Vicente , Ortlieb Luc , Sifeddine Abdel , Grados Daniel , Bertrand Arnaud
Published: November 2017

The Humboldt Current System (HCS) has the highest production of forage fish in the world, although it is highly variable and the future of the primary component, anchovy, is uncertain in the context of global warming. Paradigms based on late 20th century observations suggest that large‐scale forcing controls decadal‐scale fluctuations of anchovy and sardine across different boundary currents of the Pacific. We develop records of anchovy and sardine fluctuations since 1860 AD using fish scales from multiple sites containing laminated sediments and compare them with Pacific basin‐scale and regional indices of ocean climate variability. Our records reveal two main anchovy and sardine phases with a timescale that is not consistent with previously proposed periodicities. Rather, the regime shifts in the HCS are related to 3D habitat changes driven by changes in upwelling intensity from both regional and large‐scale forcing. Moreover, we show that a long‐term increase in coastal upwelling translates via a bottom‐up mechanism to top predators suggesting that the warming climate, at least up to the start of the 21st century, was favorable for fishery productivity in the HCS.
Maize harvest index and water use efficiency can be improved by inhibition of gibberellin biosynthesis
Authors: Hütsch B. W. , Schubert S.
Published: November 2017

Possibilities to improve maize harvest index and nutrient utilization efficiency by application of plant growth regulators were investigated. In container experiments, the effects of different growth regulators on the development of the maize (Zea mays L.) cultivars Pioneer 3906 and Fabregas were tested. Paclobutrazol (PAC) and chlorocholine chloride (CCC), two inhibitors of gibberellin biosynthesis, as well as gibberellic acid (GA3) were applied at growth stage V5. Three weeks after application of PAC, shoot growth of both maize cultivars was strongly affected with a significant decrease in plant height in the PAC treatment by 44% and 36% for Pioneer 3906 and Fabregas, respectively. The growth‐retarded plants had higher leaf areas and reduced transpiration rates. The higher shoot growth after GA3 application was accompanied by a reduction in leaf area and an increase in transpiration rate during 1 week before anthesis. CCC treatment showed no significant effects on plant height, leaf area and transpiration rate. The PAC‐treated cultivar Pioneer 3906 produced several cobs per plant, which were mainly barren at maturity. However, PAC application to Fabregas resulted in just one cob per plant with good kernel development and a grain yield, which was not significantly reduced in comparison with the control. With this similar grain yield in combination with a straw yield decrease of 32%, the harvest index was significantly improved by 12%. In addition, with PAC‐treated Fabregas plants, a 19% increased water use efficiency of the grain (WUEgrain) during the critical period of kernel setting was achieved. In this maize cultivar, CCC application also improved harvest index by 5%, but no effect on WUEgrain occurred. GA3 treatment decreased harvest index of both maize cultivars, and it either reduced WUEgrain (Pioneer 3906) or showed no effect (Fabregas). Utilization efficiencies of N, P and K were not increased with growth regulator application, even in the PAC‐treated Fabregas plants with a significantly improved allocation of assimilates to the grain, mirrored by the higher harvest index. The results indicate that fertilizer applications must be adjusted to the reduced demand of growth‐retarded plants, most likely leading to higher nutrient utilization efficiencies.
Periventricular White Matter Hyperintensities and Functional Decline
Authors: Dhamoon Mandip S. , Cheung Ying‐Kuen , Bagci Ahmet , Alperin Noam , Sacco Ralph L. , Elkind Mitchell S. V. , Wright Clinton B.
Published: November 2017

Background/Objectives

We previously showed that global brain white matter hyperintensity volume (WMHV) was associated with accelerated long‐term functional decline. The objective of the current study was to determine whether WMHV in particular brain regions is more predictive of functional decline.

Design

Prospective population‐based study.

Setting

Northern Manhattan magnetic resonance imaging (MRI) study.

Participants

Individuals free of stroke at baseline (N = 1,195; mean age 71 ± 9; n = 460 (39%) male).

Measurements

Participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences. Volumetric WMHV distribution across 14 brain regions (brainstem; cerebellum; bilateral frontal, occipital, temporal, and parietal lobes; and bilateral anterior and posterior periventricular white matter (PVWM)) was determined using a combination of bimodal image intensity distribution and atlas‐based methods. Participants had annual functional assessments using the Barthel Index (BI) (range 0–100) over a mean of 7.3 years and were followed for stroke, myocardial infarction (MI), and mortality. Because there were multiple collinear variables, least absolute shrinkage and selection operator (LASSO) regression–selected regional WMHV variables most associated with outcomes and adjusted generalized estimating equations models were used to estimate associations with baseline BI and change over time.

Results

Using LASSO regularization, only right anterior PVWM was found to meet criteria for selection, and each standard deviation greater WMHV was associated with accelerated functional decline of 0.95 additional BI points per year (95% confidence interval (CI) = −1.20 to −0.70) in an unadjusted model, −0.92 points per year (95% CI = −1.18 to −0.67) with baseline covariate adjustment, and −0.87 points per year (95% CI = −1.12 to −0.62) after adjusting for incident stroke and MI.

Conclusion

In this large population‐based study with long‐term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline.
Relationships between atypical sensory processing patterns, maladaptive behaviour and maternal stress in Spanish children with autism spectrum disorder
Authors: Nieto C. , López B. , Gandía H.
Published: November 2017

Background

This study investigated sensory processing in a sample of Spanish children with autism spectrum disorder (ASD). Specifically, the study aimed to explore (1) the prevalence and distribution of atypical sensory processing patterns, (2) the relationship between adaptive and maladaptive behaviour with atypical sensory processing and (3) the possible relationship between sensory subtype and maternal stress.

Methods

The short sensory profile 2 (Dunn 2014) and the vineland adaptive behavior scale (Sparrow et al. 1984) were administered to examine the sensory processing difficulties and maladaptive behaviours of 45 children with ASD aged 3 to 14; their mothers also completed the parenting stress index‐short form (Abidin 1995).

Results

Atypical sensory features were found in 86.7% of the children; avoider and sensor being the two most common patterns. No significant relationship was found between atypical sensory processing and adaptive behaviour. However, the analysis showed a strong relationship between sensory processing and maladaptive behaviour. Both maladaptive behaviour and sensory processing difficulties correlated significantly with maternal stress although maternal stress was predicted only by the sensory variable, and in particular by the avoider pattern.

Conclusions

The findings suggest that sensory features in ASD may be driving the high prevalence of parental stress in carers. They also suggest that the effect on parental stress that has been attributed traditionally to maladaptive behaviours may be driven by sensory difficulties. The implications of these findings are discussed in relation to the development of interventions and the need to explore contextual and cultural variables as possible sources of variability.
Can interpersonal contact help improve attitudes toward soldiers with intellectual disability? An Israeli study
Authors: Werner S.
Published: November 2017

Background

It has been argued that interpersonal contact is the best intervention for reducing negative attitudes and discrimination toward individuals with intellectual disabilities (ID). In Israel, the Equal in Uniform project makes it possible for individuals with ID to serve alongside soldiers without ID in ordinary military units in the Israeli Defense Forces. The project provided the opportunity to examine the effect of contact on the attitudes of soldiers without ID.

Methods

Data analyses are based on data collected from 220 soldiers without ID via a self‐administered questionnaire based on the Multidimensional Attitudes Scale. Of these, 138 were in contact with soldiers with ID as part of the project.

Results

A mediation model showed that the impact of contact with a soldier with ID on withdrawal behaviour was mediated by cognitive attributions and negative affect. Contact was directly associated with prosocial behaviour.

Discussion

Results support the importance of contact between soldiers with and without ID to bring about improved attitudes toward the former.
Characteristics of prisoners with intellectual disabilities
Authors: Chaplin E. , McCarthy J. , Underwood L. , Forrester A. , Hayward H. , Sabet J. , Mills R. , Young S. , Asherson P. , Murphy D.
Published: November 2017

Background

Previous studies have found high rates of intellectual disabilities (ID) in prison. However, little is understood about prisoners with ID. This study aimed to identify prisoners with ID and compare their characteristics with prisoners without neurodevelopmental disorders with regard to demographic profile, mental health, suicide risk and offences.

Method

This was a descriptive, cross‐sectional study carried out using face‐to‐face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ID and mental disorder.

Results

The study identified 18 prisoners as having ID. Participants with ID were less likely to be from a black or minority ethnic background, be over 35 years of age or have any qualifications. They were more likely to have been single, homeless or unemployed before coming into prison. Prisoners with ID were significantly more likely to have mental health problems and 25% had thought about suicide in the last month and 63% had attempted suicide in the past. Prisoners with ID were also more likely to be housed in the vulnerable prisoners' wing and significantly more likely to have committed robbery than other prisoners.

Conclusions

The findings confirm the presence of significant numbers of people with ID with high levels of mental illness in a male prison. Services across the CJS are required for this group, specifically, there is a need for raised awareness among those working in prison about ID and improved skills to recognise offenders with ID and address major gaps in current healthcare provision in prison.
Skin care and cosmeceuticals: Attitudes and trends among trainees and educators
Authors: Feetham H Jill , Jeong H Sam , McKesey Jacqueline , Wickless Heather , Jacobe Heidi
Published: November 2017

Introduction

Patients often seek skin care recommendations from their dermatologist. The objective of this study was to determine the degree of education dermatology residents receive on skin care and cosmeceutical products, the source of education, and the attitude of trainees and their educators toward skin care and cosmeceuticals.

Methods

A cross‐sectional survey of dermatology residents and faculty via an online survey administered June 2015 and August 2015, respectively.

Results

In total, 104 dermatology residents and 50 dermatology faculty members completed the survey. Among the dermatology residents and faculty, equal distribution was represented across the country. The majority of residents and faculty (62% and 69%, respectively) report discussing skin care with up to 25% of their patients. Among resident participants, 76.5% “agree or strongly agree” that skin care and cosmeceutical education should be part of their education and the majority of residents (74.5%) report their education has been “too little or nonexistent” during residency. In contrast, the majority of the faculty (60%) reports their resident education is “just the right amount or too much” (P < .001).

Conclusions

Skin care and cosmeceutical recommendations are often discussed in dermatology visits. Dermatology residents feel that education on these products should be a part of their residency training.
Labour demand and supply changes in Norway following an imposed harmonization of geographically differentiated payroll‐tax rates
Authors: Dale‐Olsen Harald
Published: November 2017

The payroll tax is an important source for public financial revenues. Utilizing Norwegian population‐wide linked‐employer‐employee register‐data for 2001–12 while exploiting the harmonizing of the geographically differentiated payroll tax imposed by the EU, I show that payroll tax increases are shifted onto workers’ hourly wages thus reducing these. Annual earnings also drop as the payroll tax grows. Neither unemployment nor employment levels are affected in the short‐run, but the payroll‐tax levels and the number of sick leave days appear positively correlated. In the long run, entry into retirement and DI rolls increase. Thus the tax hike induces the withdrawal of workers from the labour force.
The influence of lipid‐extraction and long‐term DMSO preservation on carbon (δ13C) and nitrogen (δ15N) isotope values in cetacean skin
Authors: Newsome Seth D. , Chivers Susan J. , Berman Kowalewski Michelle
Published: November 2017

Stable isotope analysis (SIA) has rapidly become a useful tool to study the ecology of wild animal populations, especially for elusive, wide‐ranging predators like marine mammals. The development of projectile biopsy techniques resulted in the collection of thousands of cetacean tissue samples that were archived in a dimethyl sulfoxide (DMSO) solution for long‐term, multidecadal preservation. Here we examine the influence of DMSO preservation on carbon (δ13C) and nitrogen (δ15N) values by comparing a set of paired delphinid skin samples stored frozen without preservative and in DMSO for up to 22 yr. Treatment of paired frozen and DMSO‐preserved skin in a 2:1 chloroform:methanol solution yielded similar δ13C and δ15N values, revealing that DMSO and lipid contamination have similar isotopic effects on skin, and that these effects can be removed using routine lipid‐extraction methods. Further, amino acid concentrations in DMSO‐preserved and frozen skin tissue were similar, providing independent evidence of minimal protein alteration due to preservation. Access to a rich archive of skin samples preserved in DMSO will expand our ability to examine temporal and spatial variability in the isotope values of cetaceans, which will aid our understanding of how their ecology has been influenced by historical changes in environmental conditions.
Elderly patients with glomerular diseases and IgA nephropathy
Authors: Lin Jing , Cheng Zhen , Qian Qi
Published: November 2017

Summary at a Glance

As the population ages, large numbers of elderly patients will present with kidney diseases. Kidney biopsy for elderly patients is generally well tolerated and informative. Compared with younger adults, IgA nephropathy in the elderly carries a poor prognosis. In patients with intercurrent infections, IgA‐dominant postinfectious GN should be carefully differentiated from idiopathic IgA nephropathy. Existing ESRD and mortality prediction models/scoring systems for IgA nephropathy may not be generalized to elderly patients.
Clinical and pathological factors associated with progression of diabetic nephropathy
Authors: Liang Shuang , Cai Guang‐Yan , Chen Xiang‐Mei
Published: November 2017

Summary at a Glance

This article reviews the values and limitations of some factors in the development and progression of diabetic kidney disease.
Repugnant Accuracy
Authors: Talbot Brian
Published: November 2017

Accuracy‐first epistemology is an approach to formal epistemology which takes accuracy to be a measure of epistemic utility and attempts to vindicate norms of epistemic rationality by showing how conformity with them is beneficial. If accuracy‐first epistemology can actually vindicate any epistemic norms, it must adopt a plausible account of epistemic value. Any such account must avoid the epistemic version of Derek Parfit's “repugnant conclusion.” I argue that the only plausible way of doing so is to say that accurate credences in certain propositions have no, or almost no, epistemic value. I prove that this is incompatible with standard accuracy‐first arguments for probabilism, and argue that there is no way for accuracy‐first epistemology to show that all credences of all agents should be coherent.
Functional and molecular outcomes of the human masticatory muscles
Authors: Isola G , Anastasi GP , Matarese G , Williams RC , Cutroneo G , Bracco P , Piancino MG
Published: November 2017

The masticatory muscles achieve a broad range of different activities such as chewing, sucking, swallowing, and speech. In order to accomplish these duties, masticatory muscles have a unique and heterogeneous structure and fiber composition, enabling them to produce their strength and contraction speed largely dependent on their motor units and myosin proteins that can change in response to genetic and environmental factors. Human masticatory muscles express unique myosin isoforms, including a combination of thick fibers, expressing myosin light chains (MyLC) and myosin class I and II heavy chains (MyHC) ‐IIA, ‐IIX, α‐cardiac, embryonic and neonatal and thin fibers, respectively. In this review, we discuss the current knowledge regarding the importance of fiber‐type diversity in masticatory muscles versus supra‐ and infrahyoid muscles, and versus limb and trunk muscles. We also highlight new information regarding the adaptive response and specific genetic variations of muscle fibers on the functional significance of the masticatory muscles, which influences craniofacial characteristics, malocclusions, or asymmetry. These findings may offer future possibilities for the prevention of craniofacial growth disturbances.
Iron Age Burial in Wales: Patterns, Practices and Problems
Authors: Davis Oliver
Published: November 2017

Until the latter part of the twentieth century, Iron Age burial in Britain was thought to be largely archaeologically invisible. However, over the last 40 years the recovery of large assemblages of human remains, often from pits and ditches rather than beneath monumental structures, has changed our understanding of Iron Age funerary practices. The problem, though, is that the majority of this material derives from core areas of study, particularly southern England and Yorkshire. Our knowledge of burial in the more peripheral areas of Britain, such as Wales, is much more poorly understood. The perceived paucity of burials from such regions is often still interpreted as resulting from the practice of archaeologically invisible disposal methods such as excarnation or the scattering of cremated remains. This paper presents a comprehensive review and analysis of Iron Age human remains in Wales. Although the resource for study is relatively small, a variety of practices, disposal methods and treatments of bodies can be recognized which challenge our current narratives. The scarcity of burials when compared to other parts of Britain, such as Wessex, is suggested to be a result of both poor preservation and bias in archaeological research strategies, rather than the dominance of an ‘invisible’ burial rite.
Recognizing the Emotion Work in Deliberation. Why Emotions Do Not Make Deliberative Democracy More Democratic
Authors: Saam Nicole J.
Published: November 2017

Critics of deliberative democracy theory have argued that deliberation should be supplemented with forms of emotional expression to eliminate the inequalities of gender, race, and class which are reproduced in deliberations that privilege rational discussion. This article presents results from a qualitative empirical study on emotion work in deliberations. Emotional expression requires emotion work on the part of the participants. The capacity for such emotion work appears to depend on the individual participant's emotional capital. The results show that, given the participants' varying levels of emotional capital, an emphasis on emotion work tends to reproduce inequalities, rather than to eliminate them.
Interviewing intoxicated witnesses: Memory performance in theory and practice
Authors: Hildebrand Karlén Malin
Published: November 2017

Memory encoding and recall involving complex, effortful cognitive processes are impaired by alcohol primarily due to impairment of a select few, but crucial, cortical areas. This review shows how alcohol affects some, but not all, aspects of eyewitnesses' oral free recall performance. The principal results, so far, are that: a) free recall reports by intoxicated witnesses (at the investigated BAC‐levels) may contain less, but as accurate, information as reports by sober witnesses; b) immediate reports given by intoxicated witnesses may yield more information compared to reports by sober witnesses given after a one week delay; c) an immediate interview may enhance both intoxicated and sober witnesses' ability to report information in a later interview; and d) reminiscence seems to occur over repeated interviews and the new information seems to be as accurate as the previously reported information. Based on this, recommendations are given for future research to enhance understanding of the multifaceted impact of alcohol on witnesses' oral free recall of violent crimes.
Exercises of dynamic stability under unstable conditions increase muscle strength and balance ability in the elderly
Authors: Hamed A. , Bohm S. , Mersmann F. , Arampatzis A.
Published: November 2017

The purpose of this study was to assess the effectiveness of a specific exercise intervention of mechanisms to control dynamic postural stability under unstable conditions in old adults. Forty‐seven old adults (65‐80 years) were assigned to 2 experimental groups (muscle strength group, n = 15; perturbation‐based group, n = 16) and a control group (n = 16). The strength group performed resistance exercises for leg and trunk muscles, while the perturbation‐based group exercised mechanisms of dynamic stability under unstable conditions. The training duration was 14 weeks, with training sessions twice a week for 1.5 hours. Muscle strength, balance ability, and balance recovery performance were investigated before and after the interventions using maximal isometric plantar flexion and knee extension contractions, the approach of the center of pressure to the anterior limits of stability and simulated forward falls. Both interventions increased balance recovery performance in simulated forward falls (81%, d = 1.50 and 80%, d = 1.08 in the muscle strength and perturbation‐based group, respectively), while the control group did not show any changes. Plantar flexor strength increased 20% (d = 0.72) in the muscle strength and 23% (d = 1.03) in the perturbation‐based group, while muscle strength of the knee extensors increased only in the muscle strength group (8%, d = 0.76). On the other hand, only the perturbation‐based group showed a significant improvement of standing balance ability (38%, d = 1.61). We conclude that a perturbation‐based training program focusing on exercising mechanisms of dynamic stability in unstable conditions has the potential to enhance muscle strength as well as sensory information processing within the motor system during sudden and static balance tasks and, as a consequence, reduce the risk of falls in old adults.
Characterization of the novel HLA‐B*48:43 allele by sequencing‐based typing
Authors: Zhang L.‐Q. , Zhou X.‐Y. , Xiao Y. , Yang X.‐Q. , Cai J.‐P.
Published: November 2017

HLA‐B*48:43 differs from HLA‐B*48:01:01:01 by two nucleotide substitutions at positions 981 and 986.
Characterisation of the novel HLA‐G null allele, HLA‐G*01:21N, in Finnish individuals
Authors: Faucher M.‐C. , Louvanto K. , Syrjänen S. , Roger M.
Published: November 2017

We identified the novel HLA‐G*01:21N null allele in Finnish Caucasian individuals.
Multiple transmissions of chromosomally integrated human herpesvirus‐6 in one family
Authors: Rashidi Armin , Obeid Karam , Hill Joshua , Warlick Erica D. , Weisdorf Daniel J.
Published: November 2017

Chromosomally integrated human herpesvirus‐6 (ciHHV‐6) can be transmitted from parent to child or via allogeneic hematopoietic cell transplantation (HCT). We report a case of ciHHV‐6 transmitted via syngeneic HCT, and vertically across 3 generations. ciHHV‐6 was transmitted from a parent to the patient and her identical twin, and from the patient to her son. The patient underwent syngeneic HCT as rescue from chemotherapy‐induced aplasia during which ciHHV‐6 was re‐transmitted to her, this time from her identical twin. This is the first report, to our knowledge, of a patient acquiring ciHHV‐6 once via germline from a parent and again via syngeneic HCT from an identical twin.
Experimental reconstruction of double‐stranded break repair‐mediated plastid DNA insertion into the tobacco nucleus
Authors: Wang Dong , Gu Jinbao , David Rakesh , Wang Zhen , Yang Songtao , Searle Iain R. , Zhu Jian‐Kang , Timmis Jeremy N.
Published: November 2017

The mitochondria and plastids of eukaryotic cells evolved from endosymbiotic prokaryotes. DNA from the endosymbionts has bombarded nuclei since the ancestral prokaryotes were engulfed by a precursor of the nucleated eukaryotic host. An experimental confirmation regarding the molecular mechanisms responsible for organelle DNA incorporation into nuclei has not been performed until the present analysis. Here we introduced double‐stranded DNA breaks into the nuclear genome of tobacco through inducible expression of I‐SceI, and showed experimentally that tobacco chloroplast DNAs insert into nuclear genomes through double‐stranded DNA break repair. Microhomology‐mediated linking of disparate segments of chloroplast DNA occurs frequently during healing of induced nuclear double‐stranded breaks (DSB) but the resulting nuclear integrants are often immediately unstable. Non‐Mendelian inheritance of a selectable marker (neo), used to identify plastid DNA transfer, was observed in the progeny of about 50% of lines emerging from the screen. The instability of these de novo nuclear insertions of plastid DNA (nupts) was shown to be associated with deletion not only of the nupt itself but also of flanking nuclear DNA within one generation of transfer. This deletion of pre‐existing nuclear DNA suggests that the genetic impact of organellar DNA transfer to the nucleus is potentially far greater than previously thought.
Modulation of fatty acid metabolism and immune suppression are features of in vitro tumour sphere formation in ontogenetically distinct dog cancers
Authors: Kim J.‐H. , Frantz A. M. , Sarver A. L. , Gorden Klukas B. H. , Lewellen M. , O'Brien T. D. , Dickerson E. B. , Modiano J. F.
Published: November 2017

Non‐adherent, 3‐dimensional sphere formation is used as an in vitro surrogate to evaluate cellular potential for tumour initiation and self‐renewal. To determine if a shared molecular program underlies the capacity for sphere formation by cells originating from diverse tumour types, we characterized molecular and functional properties of 10 independent cell lines derived from 3 ontogenetically distinct dog cancers: hemangiosarcoma, osteosarcoma and glial brain tumours. Genome‐wide gene expression profiling identified tumour‐of‐origin‐dependent patterns of adjustment to sphere formation in a uniform culture condition. However, expression of the stem/progenitor markers CD34 and CD117, resistance to cytotoxic drugs and dye efflux (side population assays) showed no association with these gene expression profiles. Instead, primary sphere‐forming capacity was inversely correlated with the ability to reform secondary spheres, regardless of tumour ontogeny. Primary sphere formation seemed to be proportional to the number of pre‐existing cells with sphere‐forming capacity in the cell lines. Cell lines where secondary sphere formation was more proficient than primary sphere formation showed enrichment of genes involved in fatty acid synthesis and immunosuppressive cytokines. In contrast, cell lines where secondary sphere formation was approximately equivalent to or less proficient than primary sphere formation showed upregulation of CD40 and enrichment of genes involved in fatty acid oxidation. Our data suggest that in vitro sphere formation is associated with upregulation of gene clusters involved in metabolic and immunosuppressive functions, which might be necessary for self‐renewal and for tumour initiation and/or tumour propagation in vivo.
Cutting Force Simulation in Minute Time Resolution for Ball End Milling Under Various Tool Posture
Authors: Nishida Isamu , Okumura Ryuma , Sato Ryuta , Shirase Keiichi
Published: November 2017

A new cutting force simulator has been developed to predict cutting force in ball end milling. In this simulator, uncut chip thickness is discretely calculated based on fully voxel models representing both cutting edge and instantaneous workpiece shape. In the previous simulator, a workpiece voxel model was used to calculate uncut chip thickness under a complex change of workpiece shape. Using a workpiece voxel model, uncut chip thickness is detected by extracting the voxels removed per cutting tooth for the amount of material fed into the cutting edge. However, it is difficult to define the complicated shape of cutting edge, because the shape of cutting edge must be defined by mathematical expression. It is also difficult to model the voxels removed by the cutting edge when tool posture is nonuniformly changed. Therefore, a new method to detect uncut chip thickness is proposed, one in which both cutting edge and instantaneous workpiece shape are fully represented by a voxel model. Our new method precisely detects uncut chip thickness at minute tool rotation angles, making it possible to detect the uncut chip thickness between the complex surface shape of the workpiece and the particular shape of the cutting edge. To validate the effectiveness of our new method, experimental five-axis milling tests using ball end mill were conducted. Estimated milling forces for several tool postures were found to be in good agreement with the measured milling forces. Results from the experimental five-axis milling validate the effectiveness of our new method.
Wave Motion Control Over Submerged Horizontal Plates
Authors: Karmakar D. , Guedes Soares C.
Published: November 2017

The interaction of surface gravity waves with horizontal pitching plate for actively control waves is investigated based on the linearized theory of water waves. The three-dimensional (3D) problem is formulated for the submerged plate pitching about its middle point and the other plate is considered to be floating above the submerged plate. The submerged plate's thickness is considered negligible in comparison with the water depth and wavelength of the incident wave. The study is carried out using the matched eigenfunction expansion method and the analytical solution is developed for the interaction of the surface gravity waves with horizontal submerged structure. The performance is analyzed for both impermeable and porous submerged pitching plate. The numerical results for the reflection coefficient, transmission coefficient, and free-surface deflection are computed and analyzed. The study is carried to find the optimal value of the length and depth of the submerged plate at which the dissipation of the incident wave energy is observed. The reduction the wave transformation due to the pitching of the plate with the change in angle of incidence is also analyzed. The present study will be helpful in the analysis of proper functioning of submerged pitching plate to control wave motion for the protection of offshore structures.
Underwater vocal complexity of Arctic sealErignathus barbatusin Kongsfjorden (Svalbard)
Authors: Parisi Ignazio , de Vincenzi Giovanni , Torri Marco , Papale Elena , Mazzola Salvatore , Bonanno Angelo , Buscaino Giuseppa
Published: November 2017

In this study the description of underwater vocal repertoire of bearded seal in Svalbard (Norway) was extended. Two autonomous passive acoustic recorders were deployed for one year (August 2014–July 2015) in the inner and outer parts of the Kongsfjorden, and 1728 h were recorded and 17 220 vocalizations were found. Nine different vocalization classes were identified and characterized using ten acoustic parameters. The calls showed heterogeneous spectral features, but share the descending trend of frequency modulation. The different classes emerged were discriminated primarily by bandwidth and duration, and then by minimum frequency, central frequency, and maximum frequency in this order. This study represents a step forward to improve the understanding of the acoustic behaviour and the social function of these calls, and identified long passive acoustic monitoring as an effective method to assess vocal complexity and the ecology of marine species producing sounds.
Antimicrobial Octapeptin C4 Analogues Active against Cryptococcus Species
Authors: Chitty Jessica L. , Butler Mark S. , Suboh Azzah , Edwards David J. , Cooper Matthew A. , Fraser James A. , Robertson Avril A. B.
Published: November 2017

Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogen
Cryptococcus neoformans
is a significant contributor to mortality, and its growing resistance to current antifungals is an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal. Octapeptin C4 was a potent, selective inhibitor of this fungal pathogen with an MIC of 1.56 μg/ml. Further testing of octapeptin C4 against 40 clinical isolates of
C. neoformans
var.
grubii
or
neoformans
showed an MIC of 1.56 to 3.13 μg/ml, while 20 clinical isolates of
C. neoformans
var.
gattii
had an MIC of 0.78 to 12.5 μg/ml. In each case, the MIC values for octapeptin C4 were equivalent to, or better than, current antifungal drugs fluconazole and amphotericin B. The negatively charged polysaccharide capsule of
C. neoformans
influences the pathogen's sensitivity to octapeptin C4, whereas the degree of melanization had little effect. Testing synthetic octapeptin C4 derivatives provided insight into the structure activity relationships, revealing that the lipophilic amino acid moieties are more important to the activity than the cationic diaminobutyric acid groups. Octapeptins have promising potential for development as anticryptococcal therapeutic agents.
Seventy-Five Years of Research on Protein Binding
Authors: Dalhoff Axel
Published: November 2017

This review summarizes evidence that the impact of protein binding of the activity of antibiotics is multifaceted and more complex than indicated by the numerical value of protein binding alone. A plethora of studies has proven that protein binding of antibiotics matters, as the free fraction only is antibacterially active and governs pharmacokinetics. Several studies have indicated that independent from protein binding of immunoglobulin G, albumin, α1-acid-glycoprotein, and pulmonary surfactant acted synergistically with antibacterial agents, thus suggesting that some intrinsic properties of serum proteins may have mediated serum-antibiotic synergisms. It has been demonstrated that IgG and albumin permeabilized Gram-negative and Gram-positive bacteria and facilitated the uptake of poorly penetrating antibiotics. Alpha-1-acid-glycoprotein and pulmonary surfactant also exerted a permeabilizing activity, but proof that this property results in a sensitizing effect is missing. The permeabilizing effect of serum proteins may explain why serum-antibiotic synergisms do not represent a general phenomenon but are limited to specific drug-bug associations only. Although evidence has been generated to support the hypothesis that native serum proteins interact synergistically with antibiotics, systematic and well-controlled studies have to be performed to substantiate this phenomenon. The interactions between serum proteins and bacterial surfaces are driven by physicochemical forces. However, preparative techniques, storage conditions, and incubation methods have a significant impact on the intrinsic activities of these serum proteins affecting serum-antibiotic synergisms, so these techniques have to be standardized; otherwise, contradictory data or even artifacts will be generated.
Pharmacokinetics and Safety of Omadacycline in Subjects with Impaired Renal Function
Authors: Berg Jolene K. , Tzanis Evan , Garrity-Ryan Lynne , Bai Stephen , Chitra Surya , Manley Amy , Villano Stephen
Published: November 2017

Many antibiotics require dose adjustments in patients with renal impairment and/or in those undergoing hemodialysis. Omadacycline, the first aminomethylcycline antibiotic in late-stage clinical development, displays activity against a broad spectrum of bacterial pathogens, including drug-resistant strains. Data from completed phase 3 studies of omadacycline for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) showed intravenous (i.v.) to once-daily oral omadacycline to be clinically effective and well tolerated. To determine if the dosing of omadacycline should be adjusted in patients with impaired renal function, a phase 1 study examining the pharmacokinetics (PK) and safety of i.v. omadacycline (100 mg) was conducted in subjects with end-stage renal disease (ESRD) on stable hemodialysis (
n
= 8) and in matched healthy subjects (
n
= 8). i.v. administration of omadacycline produced similar plasma concentration-time profiles in subjects with ESRD and healthy subjects. Further, in subjects with ESRD, similar values of the PK parameters were observed when omadacycline was administered i.v. after or before dialysis. The mean area under the concentration-time curve from time zero extrapolated to infinity in plasma was 10.30 μg · h/ml when omadacycline was administered to ESRD subjects after dialysis, 10.20 μg · h/ml when omadacycline was administered to ESRD subjects before dialysis, and 9.76 μg · h/ml when omadacycline was administered to healthy subjects. The mean maximum observed concentration of omadacycline in plasma in ESRD subjects was 1.88 μg/ml when it was administered after dialysis and 2.33 μg/ml when it was administered before dialysis, and in healthy subjects it was 1.92 μg/ml. The 100-mg i.v. dose of omadacycline was generally safe and well tolerated in both ESRD and healthy subjects. This study demonstrates that no dose adjustment is necessary for omadacycline in patients with impaired renal function or on days when patients are receiving hemodialysis.
Characterization of Stress and Innate Immunity Resistance of Wild-Type and Δp66 Borrelia burgdorferi
Authors: Curtis Michael W. , Hahn Beth L. , Zhang Kai , Li Chunhao , Robinson Richard T. , Coburn Jenifer
Published: November 2017

Borrelia burgdorferiis a causative agent of Lyme disease, the most common arthropod-borne disease in the United States.B. burgdorferievades host immune defenses to establish a persistent, disseminated infection. Previous work showed that P66-deficientB. burgdorferi(Δp66) is cleared quickly after inoculation in mice. We demonstrate that the Δp66strain is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of Δp66bacteria is not due to inherent defects in multiple properties that might affect infectivity: bacterial outer membrane integrity, motility, chemotactic response, or nutrient acquisition. This led us to the hypothesis that P66 has a role in mouse cathelicidin-related antimicrobial peptide (mCRAMP; a major skin antimicrobial peptide) and/or neutrophil evasion. Neither wild-type (WT) nor Δp66 B. burgdorferiwas susceptible to mCRAMP. To examine the role of neutrophil evasion, we administered neutrophil-depleting antibody anti-Ly6G (1A8) to C3H/HeN mice and subsequently monitored the course ofB. burgdorferiinfection. Δp66mutants were unable to establish infection in neutrophil-depleted mice, suggesting that the important role of P66 during early infection is through another mechanism. Neutrophil depletion did not affect WTB. burgdorferibacterial burdens in the skin (inoculation site), ear, heart, or tibiotarsal joint at early time points postinoculation. This was unexpected given that priorin vitrostudies demonstrated neutrophils phagocytose and killB. burgdorferi. These data, together with our previous work, suggest that despite thein vitroability of host innate defenses to killB. burgdorferi, individual innate immune mechanisms have limited contributions to controlling earlyB. burgdorferiinfection in the laboratory model used.
B Cell Presentation of Chlamydia Antigen Selects Out Protective CD4γ13 T Cells: Implications for Genital Tract Tissue-Resident Memory Lymphocyte Clusters
Authors: Johnson Raymond M. , Yu Hong , Strank Norma Olivares , Karunakaran Karuna , Zhu Ying , Brunham Robert C.
Published: November 2017

Surveillance and defense of the enormous mucosal interface with the nonsterile world are critical to protecting the host from a wide range of pathogens.Chlamydia trachomatisis an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract. The fallopian tubes and vagina are poorly suited to surveillance and defense, with limited immune infrastructure positioned near the epithelium. However, a dynamic process during clearing primary infections leaves behind new lymphoid clusters immediately beneath the epithelium. These memory lymphocyte clusters (MLCs) harboring tissue-resident memory (Trm) T cells are presumed to play an important role in protection from subsequent infections. Histologically, humanChlamydiaMLCs have prominent B cell populations. We investigated the status of genital tract B cells duringC. muridaruminfections and the nature of T cells recovered from immune mice using immune B cells as antigen-presenting cells (APCs). These studies revealed a genital tract plasma B cell population and a novel genital tract CD4 T cell subset producing both gamma interferon (IFN-γ) and interleukin-13 (IL-13). A panel of CD4 T cell clones and microarray analysis showed that the molecular fingerprint of CD4γ13 T cells includes a Trm-like transcriptome. Adoptive transfer of aChlamydia-specific CD4γ13 T cell clone completely prevented oviduct immunopathology without accelerating bacterial clearance. Existence of a CD4γ13 T cell subset provides a plausible explanation for the observation that human peripheral blood mononuclear cell (PBMC)Chlamydia-specific IFN-γ and IL-13 responses predict resistance to reinfection.
The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization
Authors: Schlachter Samantha , Seshu Janakiram , Lin Tao , Norris Steven , Parveen Nikhat
Published: November 2017

The Lyme disease-causing organism
Borrelia burgdorferi
is transmitted into the mammalian host by an infected-tick bite. Successful infection relies on the ability of this extracellular pathogen to persist and colonize different tissues.
B. burgdorferi
encodes a large number of adhesins that are able to interact with host ligands to facilitate adherence and tissue colonization. Multiple glycosaminoglycan binding proteins present in
B. burgdorferi
offer a degree of redundancy of function during infection, and this highlights the importance of glycosaminoglycans as host cell receptors for spirochete adherence. Of particular interest in this study is
Borrelia
glycosaminoglycan binding protein (Bgp), which binds to heparin-related glycosaminoglycans. The properties of a
bgp
transposon mutant and a
trans
-complemented derivative were compared to those of the wild-type
B. burgdorferi
in the
in vitro
binding assays and in infection studies using a C3H/HeJ mouse infection model. We determined that the loss of Bgp impairs spirochete adherence, infectivity, and tissue colonization, resulting in a reduction of inflammatory manifestations of Lyme disease. Although Bgp is not essential for infectivity, it is an important virulence factor of
B. burgdorferi
that allows adherence and tissue colonization and contributes to disease severity.