bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Double Staining: A Digital Approach to Immunohistochemical Quantification of Estrogen Receptor Protein in Breast Carcinoma Specimens
Authors: Lykkegaard Andersen Nina , Brügmann Anja , Lelkaitis Giedrius , Nielsen Søren , Friis Lippert Michael , Vyberg Mogens
Published: March 2017

Visual assessment of immunohistochemically detected estrogen receptor protein is prone to interobserver and intraobserver variation due to its subjective evaluation. The aim of this study was to validate a new image analysis system based on virtual double staining (VDS) by comparing visual and automated scorings of ER in tissue microarrays of breast carcinomas. Tissue microarrays were constructed of 112 consecutive resection specimens of breast carcinomas. Immunohistochemistry assays for ER and pancytokeratin was applied on separate serial sections. ER scoring was visually performed by 5 observers using the histoscore (H-score) method. The Visiopharm ER image analysis protocol (APP) software application using VDS technique was applied separating stromal cells from carcinoma and other epithelial cells based on the pancytokeratin reaction. Using color deconvolution, polynomial filters, and nuclear segmentation the APP determined the percentage of positive cells and their intensity, and calculated the resulting H-score. On the basis of 1% cutoff VDS was perfectly correlated with visual assessment (κ=1). Using H-score, a very high agreement between VDS and visual ER assessment was seen (R
2=0.950). Image analysis has the attributes to eliminate the shortcomings of visual ER evaluation by generating automated, reproducible, and objective results of ER assessment.
Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation
Authors: Agbay Rose Lou Marie C. , Torres-Cabala Carlos A. , Patel Keyur P. , Merril Eric D. , Duvic Madeleine , Quesada Andres , Prieto Victor G. , Aung Phyu P. , Loghavi Sanam , Young Ken H. , Hu Shimin , Ferrufino-Schmidt Maria C. , Tetzlaff Michael , Li Shaoying , Medeiros L. Jeffrey , Miranda Roberto N.
Published: March 2017

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.
TdT-positive Infiltrate in Inflamed Pediatric Kidney
Authors: Dunlap Jennifer B. , Cascio Michael J. , Stacey Xavier , Click Sarah , Troxell Megan L.
Published: March 2017

We encountered a patient with infantile nephrotic syndrome associated with a dense interstitial inflammatory infiltrate and prominent extramedullary hematopoiesis. Immunohistochemical analysis revealed numerous terminal deoxynucleotidyl transferase (TdT)-positive cells, which may raise concern for lymphoblastic lymphoma. Thus, we further characterized a group of pediatric kidneys with inflammation. TdT-positive nuclei were quantitated, and dual immunostains for TdT/CD79a, TdT/CD3, and TdT/CD43 were performed in a subset of cases; flow cytometry was performed in 1 case. TdT-positive nuclei were present in inflamed pediatric kidneys in 40 of 42 patients. TdT counts (average of 3 maximal high-power fields) ranged from 1 to >200, with a mean of 47. The presence and number of TdT-positive nuclei showed a strong association with younger patient age. Extramedullary hematopoiesis was identified in 11/42 patients, all under the age of 1. The presence of extramedullary hematopoiesis did not correlate with TdT count (P=0.158). Dual immunostaining and flow cytometric analysis in 1 case showed weak expression of B-cell markers and favored normal precursor B cells. Although TdT is a common marker of lymphoblastic lymphoma, we have demonstrated that TdT-positive cells may be part of the inflammatory milieu in infant kidneys. Together with cytologic, architectural, and clinical features, these data can help to avoid misinterpretation of involvement by lymphoblastic lymphoma/leukemia.
Current Approach to the Diagnosis and Emergency Department Management of Appendicitis in Children
Authors: Lipsett Susan C. , Bachur Richard G.
Published: March 2017

Concerns about radiation exposure have led to a decrease in the use of computed tomography in suspected appendicitis, with increased reliance on ultrasound. Children with suspected appendicitis should be risk stratified using a combination of clinical signs and symptoms, white blood cell count, and ultrasound in order to guide further evaluation and management. Magnetic resonance imaging is a promising imaging modality but remains costly. Ongoing research is evaluating the role of nonoperative management in children with confirmed appendicitis.
Metachronous Involvement, Diagnostic Imprecision of Serum Immunoglobulin G4 Levels, and Discordance Between Clinical and Radiological Findings in Immunoglobulin G4–Related Pachymeningitis
Authors: Waheed Waqar , Skidd Philip Michael , Borden Neil M. , Gibson Pamela C. , Babi Mohamed Ali , Tandan Rup
Published: March 2017

Immunoglobulin G4–related disease is an increasingly recognized, idiopathic systemic disorder that might be associated with elevated serum IgG4 level and tissue infiltration by IgG4-positive plasma cells. We describe the clinical features and biopsy findings in a patient who presented with features suggestive of pachymeningitis and multiple cranial neuropathies. Meningeal biopsy and other laboratory studies established the diagnosis of IgG4-related hypertrophic pachymeningitis. Despite treatment with corticosteroids and mycophenolate mofetil, the patient exhibited a fluctuating progressive course, which stabilized with rituximab, although the radiological findings persisted over 2½ years of follow-up. Our case highlights many important evolving concepts in the disorder, including unusual pathologic features, lack of correlation between serum IgG4 levels and the clinical course, and posttreatment clinicoradiological discordance. We provide potential explanations for this discrepancy, highlight the validity of novel cerebrospinal fluid studies and progressive systemic involvement despite use of immune-suppressive treatments, and emphasize the usefulness of rituximab as a disease-stabilizing agent.
Anal Penetrative Intercourse as a Risk Factor for Fecal Incontinence
Authors: Geynisman-Tan Julia , Kenton Kimberly , Leader-Cramer Alix , Dave Bhumy , Bochenska Katarzyna , Mueller Margaret , Collins Sarah Abbie , Lewicky-Gaupp Christina
Published: March 2017

Objective

The aim of the study is to investigate the relationship between anal penetrative intercourse (API) and pelvic floor symptoms, specifically, anal incontinence (AI).

Methods

This was an institutional review board–approved, cross-sectional, e-mail survey of women enrolled in the Illinois Women's Health Registry. Participants were anonymously queried about their sexual practices and the effects of these on bowel and bladder symptoms. Urinary symptoms were assessed using the urogenital distress inventory-6 and bowel symptoms with the fecal incontinence severity index (FISI).

Results

One thousand three women (mean age of 46 ± 15 years) completed the survey. Eighty percent were white, 56% were married, and 99% reported ever being sexually active. Thirty-two percent had API at least once, and 12% considered it “part of their sexual practice.” Sixty percent of the cohort reported a bothersome urinary symptom on the urogenital distress inventory-6, 70% reported AI on the FISI, and 15% reported fecal incontinence. Of women who engaged in API, 18% reported it changed their stool consistency, and 10% reported it caused AI. Having engaged in API within the last month was correlated with higher FISI scores (P = 0.05) and with fecal incontinence on the FISI (28.3% vs 14.4%; P = 0.01; odds ratio, 2.48). In addition, API was more commonly practiced among women who reported that vaginal intercourse caused dyspareunia (17% vs 12%, P = 0.05) or changes in bladder symptoms such as urgency or dysuria (44% vs 30%, P < 0.001).

Conclusions

Self-reported AI and FI (as measured by the FISI scores) are higher in women who have had API, and frequency of API may be important in determining the risk of bowel symptoms.
Extracranial origin of headache
Authors: Burstein Rami , Blake Pamela , Schain Aaron , Perry Carlton
Published: March 2017

Purpose of review

To summarize recent clinical and preclinical studies on extracranial pathophysiologies in migraine. It challenges the opinion-based notion that the headache phase of migraine occurs without input from peripheral nociceptors or is caused solely by activation of intracranial nociceptors supplying dural and cerebral vasculature.

Recent findings

Data that support a scenario by which migraine can originate extracranially include the perception of imploding headache that hurts outside the cranium, the existence of a network of sensory fibers that bifurcate from parent axons of intracranial meningeal nociceptors and reach extracranial tissues such as periosteum and pericranial muscles by crossing the calvarial bones through the sutures, the discovery of proinflammatory genes that are upregulated and anti-inflammatory genes that are down regulated in extracranial tissue of chronic migraine patients, and evidence that administration of OnabotulinumtoxinA to peripheral tissues outside the calvaria reduces frequency of migraine headache.

These findings seeks to shift clinical practice from prophylactically treating chronic migraine solely with medications that reduce neuronal excitability to treating irritated nociceptors or affected tissues. The findings also seeks to shift current research from focusing solely on central nervous system alterations and activation of meningeal nociceptors as a prerequisite for studying migraine.
Co-occurrence of migraine and atopy in children and adolescents: myth or a casual relationship?
Authors: Özge Aynur , Uluduz Derya , Bolay Hayrunnisa
Published: March 2017

Purpose of review

To clarify the causal relationship between migraine and atopic disorders in children and adolescents.

Recent findings

Migraine headache and atopic disorders including asthma are both common functional syndromes of childhood in which nature of the relationship is still debated. Attacks may induce in both disorders upon exposure to potential triggers in genetically susceptible individuals. Clinical phenotype manifests by temporary dysfunction of target tissue mediated by inflammation triggered by specific agents. Clinical features also change after puberty because of the partial effect of female sex hormones on the process. Appropriate definition of the syndrome and differentiating from other disorders are necessary not only for correct diagnosis, but also for planning of management strategies in children. Allergic rhinosinusitis needs to be differentiated from migraine even in experienced clinics. Questioning the presence of cranial autonomic symptoms is important clue in the differential diagnosis. Atopic disorder screening is particularly required in the diagnosis of migraine in childhood and adolescents. The link between both disorders of childhood seems to be far from a coincidence and some common inflammatory mechanisms are shared.

On the basis of clinical features, laboratory findings and some practical clues in children, accurate diagnosis of migraine and atopic disorders are very critical for physicians, pediatricians and algologists.
Artificial night lighting inhibits feeding in moths
Authors: van Langevelde Frank , van Grunsven Roy H. A. , Veenendaal Elmar M. , Fijen Thijs P. M.
Published: March 2017

One major, yet poorly studied, change in the environment is nocturnal light pollution, which strongly alters habitats of nocturnally active species. Artificial night lighting is often considered as driving force behind rapid moth population declines in severely illuminated countries. To understand these declines, the question remains whether artificial light causes only increased mortality or also sublethal effects. We show that moths subjected to artificial night lighting spend less time feeding than moths in darkness, with the shortest time under light conditions rich in short wavelength radiation. These findings provide evidence for sublethal effects contributing to moth population declines. Because effects are strong under various types of light compared with dark conditions, the potential of spectral alterations as a conservation tool may be overestimated. Therefore, restoration and maintenance of darkness in illuminated areas is essential for reversing declines of moth populations.
Capturing goats: documenting two hundred years of mitochondrial DNA diversity among goat populations from Britain and Ireland
Authors: Cassidy Lara M. , Teasdale Matthew D. , Carolan Seán , Enright Ruth , Werner Raymond , Bradley Daniel G. , Finlay Emma K. , Mattiangeli Valeria
Published: March 2017

The domestic goat (
Capra hircus
) plays a key role in global agriculture, being especially prized in regions of marginal pasture. However, the advent of industrialized breeding has seen a dramatic reduction in genetic diversity within commercial populations, while high extinction rates among feral herds have further depleted the reservoir of genetic variation available. Here, we present the first survey of whole mitochondrial genomic variation among the modern and historical goat populations of Britain and Ireland using a combination of mtDNA enrichment and high throughput sequencing. Fifteen historical taxidermy samples, representing the indigenous ‘Old Goat’ populations of the islands, were sequenced alongside five modern Irish dairy goats and four feral samples from endangered populations in western Ireland. Phylogenetic and network analyses of European mitochondrial variation revealed distinct groupings dominated by historical British and Irish samples, which demonstrate a degree of maternal genetic structure between the goats of insular and continental Europe. Several Irish modern feral samples also fall within these clusters, suggesting continuity between these dwindling populations and the ancestral ‘Old Goats’ of Ireland and Britain.
Edward Charles Slater. 16 January 1917 — 26 March 2016
Authors: Borst Piet
Published: March 2017

With the death of Edward Charles Slater, Bill for insiders, biochemistry loses one of the key players in the field of bioenergetics in the second half of the twentieth century. Raised in Australia and trained as a chemist, he joined the lab of David Keilin FRS in Cambridge for his PhD where he discovered a new component of the mitochondrial respiratory chain, an Fe-S protein, long known as the Slater factor. After a brief post-doc period in the lab of Severo Ochoa in New York, where Slater started studies on oxidative phosphorylation that would remain his major interest, he returned to Keilin's institute. In 1953 he formulated there his chemical hypothesis for the mechanism of oxidative phosphorylation that would dominate the field until displaced by the chemi-osmotic theory of Peter Mitchell FRS. In 1955 Slater moved to Amsterdam, The Netherlands, where he built up one of the largest and most successful biochemistry labs in Europe. He was not only an excellent biochemist, but also an outstanding mentor and a gifted administrator who turned
Biochimica et Biophysica Acta
(
BBA
) into the largest and one of the most influential biochemical journals of the 1960s and 1970s and who contributed to the governance of numerous organizations, such as the International Union of Biochemistry and Molecular Biology (IUBMB).
The nematocyst's sting is driven by the tubule moving front
Authors: Park Sinwook , Piriatinskiy Gadi , Zeevi Dan , Ben-David Jonathan , Yossifon Gilad , Shavit Uri , Lotan Tamar
Published: March 2017

The nematocyst is the explosive injection system of the phylum Cnidaria, and is one of the fastest delivery systems found in Nature. Exploring its injection mechanism is key for understanding predator–prey interactions and protection against jellyfish stinging. Here we analyse the injection of jellyfish nematocysts and ask how the build-up of the poly-γ-glutamate (pγGlu) osmotic potential inside the nematocyst drives its discharge. To control the osmotic potential, we used a two-channel microfluidic system to direct the elongating nematocyst tubule through oil, where no osmotic potential can develop, while keeping the nematocyst capsule in water at all times. In addition, the flow inside the tubule and the pγGlu concentration profiles were calculated by applying a one-dimensional mathematical model. We found that tubule elongation through oil is orders of magnitude slower than through water and that the injection rate of the nematocyst content is reduced. These results imply that the capsule's osmotic potential is not sufficient to drive the tubule beyond the initial stage. Our proposed model shows that the tubule is pulled by the high osmotic potential that develops at the tubule moving front. This new understanding is vital for future development of nematocyst-based systems such as osmotic nanotubes and transdermal drug delivery.
Strength of silk attachment toIlex chinensisleaves in the tea bagwormEumeta minuscula(Lepidoptera, Psychidae)
Authors: Wolff Jonas O. , Lovtsova Julia , Gorb Elena , Dai Zhendong , Ji Aihong , Zhao Zhihui , Jiang Nan , Gorb Stanislav N.
Published: March 2017

Silks play an important role in the life of various arthropods. A highly neglected prerequisite to make versatile use of silks is sufficient attachment to substrates. Although there have been some studies on the structure and mechanics of silk anchorages of spiders, for insects only anecdotal reports on attachment-associated spinning behaviour exist. Here, we experimentally studied the silk attachment of the pupae and last instar caterpillars of the tea bagwormEumeta minuscula(Butler 1881) (Lepidoptera, Psychidae) to the leaves of its host plantIlex chinensis. We found that the bagworms spin attachment discs, which share some structural features with those of spiders, like a plaque consisting of numerous overlaid, looped glue-coated silk fibres and the medially attaching suspension thread. Although the glue, which coats the fibres, cannot spread and adhere very well to the leaf surface, high pull-off forces were measured, yielding a mean safety factor (force divided by the animal weight) of 385.6. Presumably, the bagworms achieve this by removal of the leaf epidermis prior to silk attachment, which exposes the underlying tissue that represents a much better bonding site. This ensures a reliable attachment during the immobile, vulnerable pupal stage. This is the first study on the biomechanics and structure of silk attachments to substrates in insects.
Hypnosis lessons by stage magnetizers: Medical and lay hypnotists in Spain
Authors: Graus Andrea
Published: March 2017

During the late nineteenth century, Spanish physicians had few chances to observe how hypnosis worked within a clinical context. However, they had abundant opportunities to watch lay hypnotizers in action during private demonstrations or on stage. Drawing on the exemplary cases of the magnetizers Alberto Santini Sgaluppi (a.k.a. Alberto Das) and Onofroff, in this paper I discuss the positive influence of stage magnetizers on medical hypnosis in Spain. I argue that, owing to the absence of medical training in hypnosis, the stage magnetizers’ demonstrations became practical hypnosis lessons for many physicians willing to learn from them instead of condemning them. I conclude that Spain might be no exception in this regard, and that further research should be undertaken into practices in other countries.
Parallel analysis ofArabidopsiscircadian clock mutants reveals different scales of transcriptome and proteome regulation
Authors: Graf Alexander , Coman Diana , Uhrig R. Glen , Walsh Sean , Flis Anna , Stitt Mark , Gruissem Wilhelm
Published: March 2017

The circadian clock regulates physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have integrated RNA-sequencing and protein mass spectrometry data to comparatively analyse thelhycca1,prr7prr9,giandtoc1circadian clock mutant rosette at the end of day and end of night. Each mutant affects specific sets of genes and proteins, suggesting that the circadian clock regulation is modular. Furthermore, each circadian clock mutant maintains its own dynamically fluctuating transcriptome and proteome profile specific to subcellular compartments. Most of the measured protein levels do not correlate with changes in their corresponding transcripts. Transcripts and proteins that have coordinated changes in abundance are enriched for carbohydrate- and cold-responsive genes. Transcriptome changes in all four circadian clock mutants also affect genes encoding starch degradation enzymes, transcription factors and protein kinases. The comprehensive transcriptome and proteome datasets demonstrate that future system-driven research of the circadian clock requires multi-level experimental approaches. Our work also shows that further work is needed to elucidate the roles of post-translational modifications and protein degradation in the regulation of clock-related processes.
Scrounging by foragers can resolve the paradox of enrichment
Authors: Toyokawa Wataru
Published: March 2017

Theoretical models of predator–prey systems predict that sufficient enrichment of prey can generate large amplitude limit cycles, paradoxically causing a high risk of extinction (the paradox of enrichment). Although real ecological communities contain many gregarious species, whose foraging behaviour should be influenced by socially transmitted information, few theoretical studies have examined the possibility that social foraging might resolve this paradox. I considered a predator population in which individuals play the producer–scrounger foraging game in one-prey-one-predator and two-prey-one-predator systems. I analysed the stability of a coexisting equilibrium point in the one-prey system and that of non-equilibrium dynamics in the two-prey system. The results revealed that social foraging could stabilize both systems, and thereby resolve the paradox of enrichment when scrounging behaviour (i.e. kleptoparasitism) is prevalent in predators. This suggests a previously neglected mechanism underlying a powerful effect of group-living animals on the sustainability of ecological communities.
Evidence for a genetic sex determination in Cnidaria, the Mediterranean red coral (Corallium rubrum)
Authors: Pratlong M. , Haguenauer A. , Chenesseau S. , Brener K.  , Mitta G. , Toulza E. , Bonabaud M. , Rialle S.  , Aurelle D. , Pontarotti P.
Published: March 2017

Sexual reproduction is widespread among eukaryotes, and the sex-determining processes vary greatly among species. While genetic sex determination (GSD) has been intensively described in bilaterian species, no example has yet been recorded among non-bilaterians. However, the quasi-ubiquitous repartition of GSD among multicellular species suggests that similar evolutionary forces can promote this system, and that these forces could occur also in non-bilaterians. Studying sex determination across the range of Metazoan diversity is indeed important to understand better the evolution of this mechanism and its lability. We tested the existence of sex-linked genes in the gonochoric red coral (Corallium rubrum, Cnidaria) using restriction site-associated DNA sequencing. We analysed 27 461 single nucleotide polymorphisms (SNPs) in 354 individuals from 12 populations including 53 that were morphologically sexed. We found a strong association between the allele frequencies of 472 SNPs and the sex of individuals, suggesting an XX/XY sex-determination system. This result was confirmed by the identification of 435 male-specific loci. An independent test confirmed that the amplification of these loci enabled us to identify males with absolute certainty. This is the first demonstration of a GSD system among non-bilaterian species and a new example of its convergence in multicellular eukaryotes.
Perceived duration of brief visual events is mediated by timing mechanisms at the global stages of visual processing
Authors: Beattie Lee , Curran William , Benton Christopher P. , Harris Julie M. , Hibbard Paul B.
Published: March 2017

There is a growing body of evidence pointing to the existence of modality-specific timing mechanisms for encoding sub-second durations. For example, the duration compression effect describes how prior adaptation to a dynamic visual stimulus results in participants underestimating the duration of a sub-second test stimulus when it is presented at the adapted location. There is substantial evidence for the existence of both cortical and pre-cortical visual timing mechanisms; however, little is known about where in the processing hierarchy the cortical mechanisms are likely to be located. We carried out a series of experiments to determine whether or not timing mechanisms are to be found at the global processing level. We had participants adapt to random dot patterns that varied in their motion coherence, thus allowing us to probe the visual system at the level of motion integration. Our first experiment revealed a positive linear relationship between the motion coherence level of the adaptor stimulus and duration compression magnitude. However, increasing the motion coherence level in a stimulus also results in an increase in global speed. To test whether duration compression effects were driven by global speed or global motion, we repeated the experiment, but kept global speed fixed while varying motion coherence levels. The duration compression persisted, but the linear relationship with motion coherence was absent, suggesting that the effect was driven by adapting global speed mechanisms. Our results support previous claims that visual timing mechanisms persist at the level of global processing.
Mechanics of ultrasound elastography
Authors: Li Guo-Yang , Cao Yanping
Published: March 2017

Ultrasound elastography enables
in vivo
measurement of the mechanical properties of living soft tissues in a non-destructive and non-invasive manner and has attracted considerable interest for clinical use in recent years. Continuum mechanics plays an essential role in understanding and improving ultrasound-based elastography methods and is the main focus of this review. In particular, the mechanics theories involved in both static and dynamic elastography methods are surveyed. They may help understand the challenges in and opportunities for the practical applications of various ultrasound elastography methods to characterize the linear elastic, viscoelastic, anisotropic elastic and hyperelastic properties of both bulk and thin-walled soft materials, especially the
in vivo
characterization of biological soft tissues.
A behavioural framework for the evolution of feeding in predatory aquatic mammals
Authors: Hocking David P. , Marx Felix G. , Park Travis , Fitzgerald Erich M. G. , Evans Alistair R.
Published: March 2017

Extant aquatic mammals are a key component of aquatic ecosystems. Their morphology, ecological role and behaviour are, to a large extent, shaped by their feeding ecology. Nevertheless, the nature of this crucial aspect of their biology is often oversimplified and, consequently, misinterpreted. Here, we introduce a new framework that categorizes the feeding cycle of predatory aquatic mammals into four distinct functional stages (prey capture, manipulation and processing, water removal and swallowing), and details the feeding behaviours that can be employed at each stage. Based on this comprehensive scheme, we propose that the feeding strategies of living aquatic mammals form an evolutionary sequence that recalls the land-to-water transition of their ancestors. Our new conception helps to explain and predict the origin of particular feeding styles, such as baleen-assisted filter feeding in whales and raptorial ‘pierce’ feeding in pinnipeds, and informs the structure of present and past ecosystems.
A maternal-effect genetic incompatibility inCaenorhabditis elegans
Authors: Ben-David Eyal , Burga Alejandro , Kruglyak Leonid
Published: March 2017

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing a genetic incompatibility between strains of the nematodeCaenorhabditis elegans.The element is made up ofsup-35,a maternal-effect toxin that kills developing embryos, andpha-1, its zygotically expressed antidote.pha-1has long been considered essential for pharynx development based on its mutant phenotype, but this phenotype in fact arises from a loss of suppression ofsup-35toxicity. Inactive copies of thesup-35/pha-1element show high sequence divergence from active copies, and phylogenetic reconstruction suggests that they represent ancestral stages in the evolution of the element. Our results suggest that other essential genes identified by genetic screens may turn out to be components of selfish elements.
Reconstruction of cell lineages and behaviors underlying arthropod limb outgrowth with multi-view light-sheet imaging and tracking
Authors: Wolff Carsten , Tinevez Jean-Yves , Pietzsch Tobias , Stamataki Evangelia , Harich Benjamin , Preibisch Stephan , Shorte Spencer , Keller Philipp J. , Tomancak Pavel , Pavlopoulos Anastasios
Published: March 2017

During development coordinated cell behaviors orchestrate tissue and organ morphogenesis to suit the lifestyle of the organism. We have used here the crustaceanParhyale hawaiensisto study the cellular basis of limb development. TransgenicParhyaleembryos with fluorescently labeled nuclei were imaged at high spatiotemporal resolution with multi-view light-sheet fluorescence microscopy over several days of embryogenesis spanning appendage morphogenesis from early specification up to late differentiation stages. Cell tracking with a new tool called Massive Multi-view Tracker (MaMuT) enabled the reconstruction of the complete cell lineage of an outgrowing thoracic limb with single-cell resolution.In silicoclonal analyses suggested that the limb primordium becomes subdivided from an early stage first into anterior-posterior and then into dorsal-ventral compartments whose boundaries intersect at the distal tip of the growing limb. Limb bud formation is associated with the spatial modulation of cell proliferation, while limb elongation is also driven by the preferential orientation of division of epidermal cells along the proximal-distal axis of growth. Cellular reconstructions were predictive of the expression patterns of limb development genes including the Decapentaplegic (Dpp) morphogen.

HIGHLIGHTS

Multi-view light-sheet microscopy of crustacean embryos from speciesParhyale hawaiensisare ideal for cellular-level analysis of organ morphogenesis.

Lineages of 3-dimensional organs were reconstructed at single-cell resolution with the Fiji/ImageJ plugin Massive Multi-view Tracker.

TheParhyalelimb primordium undergoes early lineage restrictions associated with particular cell behaviors and patterns of gene expression.

Differential rates of cell proliferation and oriented cell divisions guide appendage proximal-distal outgrowth.
Integrating functional genomics to accelerate mechanistic personalized medicine
Authors: Tyner Jeffrey W.
Published: March 2017

The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns.
Cryopreparation and Electron Tomography of Yeast Cells
Authors: O’Toole Eileen T. , Giddings Thomas H. , Winey Mark
Published: March 2017

Three-dimensional imaging of cells using electron tomography enables analysis of cell structure at unprecedented resolution. The preparation of cells for tomography using rapid freezing followed by freeze-substitution is an essential first step to ensure the optimal preservation of the cell structure for 3D studies. This protocol outlines a method for obtaining well-preserved cells using high-pressure freezing followed by freeze-substitution. We have found that this method is particularly well suited for electron tomography studies and has the added bonus of preserving antigenicity for immuno-electron microscopy. The steps involved in imaging cells and performing tomographic analysis of cellular structures are also outlined.
Large-Scale Purification of Small Ubiquitin-Like Modifier (SUMO)-Modified Proteins from Schizosaccharomyces pombe
Authors: Nie Minghua , Boddy Michael N.
Published: March 2017

Covalent protein modification by sumoylation (i.e., addition of small ubiquitin-like modifiers [SUMOs]) regulates a broad spectrum of critical functions in eukaryotic cells; however, usually ≤1% of a given protein is modified as a result of the highly dynamic nature of sumoylation. As such, capturing and identifying sumoylated proteins are both important in biological studies and very challenging tasks. Here we report a tailored purification protocol that includes rapid and complete cell disruption, coupled to highly stringent isolation of sumoylated proteins. Proteins purified using this protocol are compatible with common downstream applications such as western and mass spectrometry analyses. This protocol will work equally well to study other key covalent modifiers such as ubiquitin and Ned8.
Improved Tandem Affinity Purification Tag and Methods for Isolation of Proteins and Protein Complexes from Schizosaccharomyces pombe
Authors: Zilio Nicola , Boddy Michael N.
Published: March 2017

The tandem affinity purification (TAP) method uses an epitope that contains two different affinity purification tags separated by a site-specific protease site to isolate a protein rapidly and easily. Proteins purified via the TAP tag are eluted under mild conditions, allowing them to be used for structural and biochemical analyses. The original TAP tag contains a calmodulin-binding peptide and the IgG-binding domain from protein A separated by a tobacco etch virus (TEV) protease cleavage site. After capturing the Protein A epitope on an IgG resin, bound proteins are released by incubation with the TEV protease and then isolated on a calmodulin matrix in the presence of calcium; elution from this resin is achieved by chelating calcium with EGTA. However, because the robustness of the calmodulin-binding step in this procedure is highly variable, we replaced the calmodulin-binding peptide with three copies of the FLAG epitope, (3× FLAG)–TEV–Protein A, which can be isolated using an anti-FLAG resin. Elution from this matrix is achieved in the presence of an excess of a 3× FLAG peptide. In addition to allowing proteins to be released under mild conditions, elution by the 3× FLAG peptide adds an extra layer of specificity to the TAP procedure, because it liberates only FLAG-tagged proteins.
Isolation of High-Molecular-Weight DNA from Mammalian Tissues Using Proteinase K and Phenol
Authors: Green Michael R. , Sambrook Joseph
Published: March 2017

This procedure is the method of choice for purification of genomic DNA from mammalian tissues when large amounts of DNA are required, for example, for Southern blotting.
Mouse Ovary Cryopreservation
Authors: Sztein Jorge
Published: March 2017

Ovary cryopreservation in combination with orthotopic ovary transplantation can produce live offspring and complement embryo and sperm cryopreservation programs. One method for ovary cryopreservation is described here.
Whole-Genome Sequencing: Automated, Indexed Library Preparation
Authors: Mardis Elaine , McCombie W. Richard
Published: March 2017

This protocol describes an automated procedure for constructing an indexed Illumina DNA library. With this method, genomic DNA fragments are produced by sonication, using high-frequency acoustic energy to shear DNA. Double-stranded DNA (dsDNA) will fragment when exposed to the energy of adaptive focused acoustic shearing (AFA). The resulting DNA fragments are ligated to adaptors, amplified by polymer chain reaction (PCR), and subjected to size selection using magnetic beads. The product is suitable for use as template in whole-genome sequencing.
Peak-Finding Algorithms
Authors: Hung Jui-Hung , Weng Zhiping
Published: March 2017

Microarray and next-generation sequencing technologies have greatly expedited the discovery of genomic DNA that can be enriched using various biochemical methods. Chromatin immunoprecipitation (ChIP) is a general method for enriching chromatin fragments that are specifically recognized by an antibody. The resulting DNA fragments can be assayed by microarray (ChIP-chip) or sequencing (ChIP-seq). This introduction focuses on ChIP-seq data analysis. The first step of analyzing ChIP-seq data is identifying regions in the genome that are enriched in a ChIP sample; these regions are called peaks.
Simulations and experimental demonstrations of encoding for X-ray coherent scattering
Authors: Prokopiou Danae , Smith Kerrie L. , Rogers Keith , Paula Priscila , Evans Paul , Dicken Anthony , Godber Simon
Published: March 2017

Diffraction data may be measured using approaches that lead to ambiguity in the interpretation of scattering distributions. Thus, the encoding and decoding of coherent scattering distributions have been considered with a view to enabling unequivocal data interpretation. Two encoding regimes are considered, where encoding occurs between the X-ray source and sample, and where the encoder is placed between the sample and detector. In the first case, the successful recovery of diffraction data formed from the interrogation of powder samples with annular incident beams is presented using a coded aperture approach. In the second regime, encoding of Debye cones is shown to enable recovery of the sample position relative to the detector. The errors associated with both regimes are considered and the advantages of combining the two discussed.
Design and validation of a trust-based opportunity-enabled risk management system
Authors: Aldini Alessandro , Seigneur Jean-Marc , Ballester Lafuente Carlos , Titi Xavier , Guislain Jonathan
Published: March 2017

Purpose

The Bring-Your-Own-Device (BYOD) paradigm favors the use of personal and public devices and communication means in corporate environments, thus representing a challenge for the traditional security and risk management systems. In this dynamic and heterogeneous setting, the purpose of this paper is to present a methodology called opportunity-enabled risk management (OPPRIM), which supports the decision-making process in access control to remote corporate assets.

Design/methodology/approach

OPPRIM relies on a logic-based risk policy model combining estimations of trust, threats and opportunities. Moreover, it is based on a mobile client – server architecture, where the OPPRIM application running on the user device interacts with the company IT security server to manage every access request to corporate assets.

Findings

As a mandatory requirement in the highly flexible BYOD setting, in the OPPRIM approach, mobile device security risks are identified automatically and dynamically depending on the specific environment in which the access request is issued and on the previous history of events.

Originality/value

The main novelty of the OPPRIM approach is the combined treatment of threats (resp., opportunities) and costs (resp., benefits) in a trust-based setting. The OPPRIM system is validated with respect to an economic perspective: cost-benefit sensitivity analysis is conducted through formal methods using the PRISM model checker and through agent-based simulations using the Anylogic framework.
Cloud computing assurance – a review of literature guidance
Authors: von Solms Rossouw , Willett Melanie
Published: March 2017

Purpose

This paper aims to provide guidance on cloud computing assurance from an IT governance point of view. The board and executive management are tasked with ensuring proper governance of organizations, which should in the end contribute to a sense of assurance. Assurance is understood to be a part of corporate governance which provides stakeholders with confidence in a subject matter by evaluating evidence about that subject matter. Evidence will include proof that proper controls and structures are in place, that risks are managed and that compliance with internal and external requirements is demonstrated with regard to the subject matter. Decisions regarding the use of cloud computing in organizations bring these responsibilities to the fore.

Design/methodology/approach

The design of this paper is based on an extensive review of literature, predominantly best practices and standards, from the fields covering IT governance, cloud computing and assurance.

Findings

The results from this paper can be used to formulate cloud computing assurance evidence statements, as part of IT governance mandates.

Originality/value

This paper aims to add value by highlighting the responsibility of managers to ensure assurance when exploiting opportunities presented through IT advances, such as cloud computing; serving to inform management about the advances that have and are being made in the field of cloud computing guidelines; and motivating that these guidelines be used for assurance on behalf of organizations adopting and using cloud computing.
The changing IFRS debate in the USA: a rejoinder
Authors: Negash Minga , Holt Andrew , Hathorn John
Published: March 2017

Purpose

The debate on whether global accounting standards are appropriate for use within the US regulatory environment has not yet ended. Nearly four years after the release of the Securities and Exchange Commission’s (SEC’s) much awaited report on the issue, the position of the regulator is still unclear, and the US accounting community is uncertain about the potential for accounting change. This paper aims to examine the documented reasons for the absence of direction and clarity on this issue.

Design/methodology/approach

Using the theoretical and empirical contributions of prior research on International Financial Reporting Standards (IFRS), this study explores the potential for US adoption of IFRS by examining the main arguments forwarded by the Office of the Chief Accountant of the SEC and the International Accounting Standards Board’s response to the issues raised and by capturing the opinions of 22 graduate and 32 undergraduate students as surrogates for future practicing accountants. The student data were collected from homework submissions to an essay on US accounting convergence with IFRS.

Findings

From the analysis, the authors make four observations. First, the deliberations over IFRS adoption in the USA are not sufficiently grounded on principles of recognition, measurement and disclosure. Second, the evidence does not support the notion that IFRS is of inferior quality to current US generally accepted accounting principles. Third, the problem areas stem from the apparent divergence of the objectives ascribed to financial statements, the independence and public accountability of the global standard setter and standards that are connected with the regulation of the finance and insurance industries. The final observation is the political process of managing change in the standard setting/adoption process in the USA.

Originality/value

This paper provides a comprehensive appraisal and a change management perspective to the ongoing IFRS debate in the USA by soliciting and documenting the opinions of future practicing accountants.
Impact of performance audit on the Administration: a Belgian study (2005-2010)
Authors: Desmedt Ella , Morin Danielle , Pattyn Valérie , Brans Marleen
Published: March 2017

Purpose

This study of the impact of Belgian Court of Audit on Federal Administration for the 2005 to 2010 period aims to highlight the auditors’ influence on the management of governmental organizations through the performance audits they have been conducting since 1998. A set of ten variables allows us to measure the three types of uses of performance auditors’ work by auditees: instrumental, conceptual and strategic use.

Design/methodology/approach

A survey was sent out to a total of 148 respondents identified by the authorities of the targeted organizations; 47 usable questionnaires were completed (32 per cent response rate).

Findings

The Court of Audit’s impact on the audited entities did not provoke radical changes in the auditees’ organizational life, but the intervention of the auditors was nevertheless noticeable. The nature of the impact was rather conceptual than strategic or instrumental. And the negative consequences on auditees anticipated in the literature were not observed.

Research limitations/implications

Given the five-year period covered by the study which was made in 2014 (four years after 2010), it had to deal with the mortality of respondents and the loss of organizational memory.

Practical implications

The study gives more accurate insights about the influence that Supreme Audit Institutions (SAIs) actually exert on audited Administrations through their performance audits.

Originality/value

Because SAIs have been mandated to evaluate the government’s economy, efficiency and effectiveness for almost 40 years in the Western democracies, it is mandatory that their actual ability to influence Administrations be documented more abundantly and independently by academic researchers.