bluuebunny/crossref_metadata_2025 huggingface dataset:
Fresh frozen cadaver workshops for advanced vascular surgical training
Authors: Jansen Shirley , Cowie Margaret , Linehan John , Hamdorf Jeffery M.
Published: August 2013

Background

Reduction in working hours, streamlined training schemes and increasing use of endovascular techniques has meant a reduction in operative experience for newer vascular surgical trainees, especially those exposures which are not routinely performed such as thoracoabdominal, thoracotomy and retroperitoneal aortic, for example.

Methods

This paper describes an Advanced Anatomy of Exposure course which was designed and convened at the Clinical Training & Evaluation Centre in Western Australia and uses fresh frozen cadavers. Feedback was obtained from the participants who attended over three courses by questionnaire.

Results

Feedback was strongly positive for the course meeting both its learning outcomes and personal learning objectives, and in addition, making a significant contribution to specialty skills. Most participants thought the fresh frozen cadaveric model significantly improved the learning objectives for training.

Conclusions

The fresh frozen cadaver is an excellent teaching model highly representative of the living open surgical scenario where advanced trainees and newly qualified consultants can improve their operative confidence and consequently patient safety in vascular surgery. An efficient fresh frozen cadaver teaching programme can benefit many health professionals simultaneously maximizing the use of donated human tissue.
Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B‐dependent dephosphorylation of protein kinase C
Authors: Ching L.‐C. , Zhao J.‐F. , Su K.‐H. , Shyue S.‐K. , Hsu C.‐P. , Lu T.‐M. , Lin S.‐J. , Lee T.‐S.
Published: August 2013

Aims

We investigated the effects and underlying molecular mechanism of transient receptor potential vanilloid 1 (TRPV1), a calcium (Ca2+)‐permeable non‐selective cation channel, on phosphorylation of endothelial nitric oxide synthase (eNOS) at threonine 497 (Thr497) in bovine aortic endothelial cells (BAECs) and in mice.

Methods

Western blotting and immunoprecipitation were used for the evaluation of protein phosphorylation; protein phosphatase 2B (PP2B) activity was assessed by convention kit; Griess assay was for NO production; tube formation and Matrigel plug assay were used for angiogenesis.

Results

In BAECs, treatment with the TRPV1 ligand evodiamine decreased the phosphorylation of eNOS at Thr497, protein kinase Cα (PKCα) at Serine 657 (Ser657) and PKCβ2 at Ser660. Evodiamine increased protein phosphatase 2B (PP2B) activity and promoted the formation of a PP2B–PKC complex. Inhibition of TRPV1 activation by the pharmacological antagonists, removal of extracellular Ca2+ or pharmacological inhibition of PI3K/Akt/calmodulin‐dependent protein kinase II/AMP‐activated protein kinase signalling pathway abolished the evodiamine‐induced alterations in phosphorylation of eNOS at Thr497, PKCα at Ser657, PKCβ2 at Ser660 and PP2B activity, as well as the formation of a PP2B–PKC complex. Inhibition of PP2B activation partially reduced the evodiamine‐induced NO bioavailability and tube formation in endothelial cells (ECs) and angiogenesis in mice. Moreover, evodiamine decreased the phosphorylation of eNOS at Thr497, PKCα at Ser657 and PKCβ2 at Ser660 in apolipoprotein E (ApoE)‐deficient mouse aortas but not TRPV1‐deficient or ApoE/TRPV1 double‐knockout mice.

Conclusion

TRPV1 activation in ECs may elicit a Ca2+‐dependent effect on PP2B–PKC signalling, which leads to dephosphorylation of eNOS at Thr497 in ECs and in mice.
Effect of testosterone replacement therapy on cardiac performance and oxidative stress in orchidectomized rats
Authors: Eleawa S. M. , Sakr H. F. , Hussein A. M. , Assiri A. S. , Bayoumy N. M. K. , Alkhateeb M.
Published: August 2013

Aim

To investigate the effects of testosterone on myocardial contractility, oxidative stress status and expression of sodium channel protein (Nav1.5) and inward rectifying K channels (Kir 2.x) in normal and orchidectomized (ORX) rats.

Methods

One hundred four rats were randomly assigned into four groups (n = 26, each) as follows: (i) untreated controls, (ii) testosterone treated, (iii) orchidectomized rats and (iv) orchidectomized, testosterone‐treated rats. Treatments with the vehicle or testosterone were carried out for 12 weeks, three times per week. At the end of treatment, surface ECG, isolated heart, tissue oxidative stress and lipid peroxidation experiments were carried out on the cardiac tissues. Also, immunohistochemical examination for Nav1.5 and PCR detection of mRNA of Kir2.1, Kir2.2 and Kir2.4 subunits of K channels were carried out.

Results

Orchidectomy impaired cardiac contractile function parameters left ventricular developed pressure (LVDP) and the peaks of the positive and negative pressure derivatives (dP/dtmax and −dP/dtmax respectively), increased heart rate and prolonged QT and QTc intervals, elevated pro‐oxidant state in rat's hearts and decreased the expression of Kir 2.1 but not Kir2.2, Kir 2.4 and Nav1.5 channels. Exogenous testosterone administration to orchidectomized rats restored heart contractility and shortened QT and QTc intervals to their normal values, ameliorated the generated pro‐oxidant state and improved the expression of Nav1.5 and Kir2.1, but not Kir2.2 or Kir2.4 channels.

Conclusion

Testosterone improved cardiac contractility and shortened QT and QTc intervals in ORX rats. An effect that might be dependent of reduction in oxidative stress and enhancement of Kir2.1 channels but independent of Nav1.5 channel protein.
Recent Advances in the Search for Novel 5‐Lipoxygenase Inhibitors
Authors: Steinhilber Dieter , Hofmann Bettina
Published: August 2013

5‐Lipoxygenase (5‐LO) is an important enzyme of the arachidonic acid cascade and catalyses with the help of FLAP, the 5‐LO‐activating protein, the formation of bioactive leukotrienes (LTs). LTs are inflammatory mediators playing a pathophysiological role in different diseases such as asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer. Up to now, only one 5‐LO inhibitor is on the market, zileuton for the treatment of asthma. With the rising number of indications for anti‐LT therapy, 5‐LO inhibitor drug development becomes more and more important. This MiniReview gives an update on 5‐LO inhibitors currently under clinical development. Furthermore, the recent advances in the search for novel 5‐lipoxygenase inhibitors with a focus on computational methods are summarized. Currently, licofelone is the compound with the highest clinical development status (completed phase III trials). 5‐LO inhibitor screening programmes based on computational methods could deliver several promising drug‐like new molecules. These activities can be expected to be driven by the newly resolved structure of human 5‐LO in the future, enabling structure‐based drug design. For the prospective drugs in late‐stage clinical development, the future will show their clinical safety and efficacy in the particular diseases.
Molecular analysis for patients with IL‐12 receptor β1 deficiency
Authors: Ramirez‐Alejo N. , Blancas‐Galicia L. , Yamazaki‐Nakashimada M. , García‐Rodríguez S.E. , Rivas‐Larrauri F. , Paolo‐Cienfuegos D.P. , Alcantara‐Salinas A. , Espinosa‐Rosales F. , Santos‐Argumedo L.
Published: August 2013

Autosomal recessive interleukin‐12 receptor β1 (IL‐12Rβ1) deficiency has been described as the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), characterized by clinical disease due to weakly virulent mycobacteria such as Bacille Calmette–Guérin (BCG) vaccines and environmental mycobacteria (EM) in children who are normally resistant to most infectious agents. Here, we report the cases of five patients with mycobacterial infection, including one with systemic lupus erythematosus (SLE). Blood samples from patients and healthy controls were activated in vitro with BCG, BCG+IL‐12, and BCG+IFN‐γ. The results showed reduced or no production of IFN‐γ after IL‐12 stimulation in all samples. IL‐12Rβ1 expression on the cell surface was negligible or absent. Genetic analysis showed five novel mutations.
Chemical burns caused by trifluoroacetic acid
Authors: Dahlin Jakob , Engfeldt Malin , Svedman Cecilia , Mowitz Martin , Zimerson Erik , Isaksson Marléne , Hindsén Monica , Bruze Magnus
Published: August 2013

Background

Trifluoroacetic acid is a very strong carboxylic acid. The acid has been suspected to have similar toxic effects as hydrofluoric acid on skin contact. Hydrofluoric acid is highly toxic, owing to skin penetration by fluoride ions. A spill of hydrofluoric acid on the skin may be fatal. As trifluoroacetic acid contains fluorine, patients with chemical burns caused by trifluoroacetic acid have been given particular attention when treated in the hospital.

Objectives

To gather the known cases of trifluoroacetic acid burns from our department to give an overview of how they were exposed, the clinical presentation, and treatment.

Methods

Five patients with chemical skin burns caused by trifluoroacetic acid were reviewed with regard to the extent of the burn, treatment, blood samples taken, and systemic effects.

Results

The chemical burns reported were limited (< 1% of the total body surface). The burns healed as expected for chemical burns caused by acids. None of the patients showed any symptoms or signs that are typical for hydrofluoric acid burns.

Conclusion

Localized chemical burns caused by trifluoroacetic acid should be regarded as being similar to burns from other acids, with the exception of hydrofluoric acid. To our knowledge, there are no indications that trifluoroacetic acid causes the same toxic effects as hydrofluoric acid.
The cosmetic allergy conundrum: inference of an immunoregulatory response to cosmetic allergens
Authors: McFadden John P. , White Ian R. , Basketter David , Puangpet Pailin , Kimber Ian
Published: August 2013

The ability to be sensitized to experimental contact allergens declines significantly with increasing age, from as early as age 40 years. In contrast, the rate of contact allergy to chemical allergens (haptens) in cosmetic products significantly increases with age. This has been explained previously on the basis of greater cumulative exposure in the older age groups. However, outbreaks of contact allergy to preservatives in cosmetic products recorded soon after their introduction to the market have also shown a significantly higher rate among older adult age groups. This association with increasing age cannot be readily explained by exposure history or pattern, and is not compatible with a sensitizing/stimulatory reaction that degrades with age as the sole immune response. From this, the existence of a second, tolerizing/regulatory arm to the immune response to cutaneous haptens that possibly becomes less effective with age at a higher rate than the sensitizing/stimulatory arm can be inferred. This reinforces the view that current clinical and experimental observations of allergic contact dermatitis are best explained by an immune system with the functional ability to produce both sensitizing/stimulatory and tolerizing/regulatory responses.
Stapled vs hand suture closure of loop ileostomy: a meta‐analysis
Authors: Gong J. , Guo Z. , Li Y. , Gu L. , Zhu W. , Li J. , Li N.
Published: August 2013

Aim

Loop ileostomies are widely used in colorectal surgery to reduce the consequences of distal anastomotic failure. The optimal surgical technique for their closure has yet not been defined. A meta‐analysis was performed to compare the outcome after stapled or hand sutured ileostomy closure.

Method

An electronic literature search of EMBASE, PubMed and the Cochrane Library was undertaken to identify studies reporting stapled and hand sutured ileostomy closure. End‐points included postoperative small bowel obstruction (SBO), anastomotic leakage, wound infection, overall postoperative complications, operation time, hospital stay and surgery‐related cost.

Results

Fourteen studies including 5084 patients were identified. Meta‐analysis showed that stapled closure was associated with a lower rate of SBO overall (OR = 0.56, P < 0.00001) and early (within 30 days of closure) SBO (OR = 0.51, P < 0.00001). This difference persisted for direct ileostomy closure (OR = 0.62, P = 0.02) or closure with bowel resection and hand sewn anastomosis (OR = 0.44, P < 0.00001). Stapled closure required a shorter inpatient stay (mean difference −1.22, P < 0.0001) and operating time (mean difference −11.21, P = 0.01). No significant difference was noted between the two techniques in terms of anastomotic leakage, wound infection, overall complications or cost.

Conclusion

Stapled side‐to‐side anastomosis is associated with fewer complications, especially SBO, than hand sewn ileostomy closure by direct suture or resection and anastomosis. It is quicker to perform and associated with fewer postoperative bowel obstructions.
The Future of Design Thinking in Australia: Barriers and Opportunities
Authors: Sobel Leanne , Groeger Lars
Published: August 2013

The struggle to bring design thinking to the Australian continent encapsulates some issues that should be familiar to us all.
Spatial memory and animal movement
Authors: Fagan William F. , Lewis Mark A. , Auger‐Méthé Marie , Avgar Tal , Benhamou Simon , Breed Greg , LaDage Lara , Schlägel Ulrike E. , Tang Wen‐wu , Papastamatiou Yannis P. , Forester James , Mueller Thomas
Published: August 2013

Memory is critical to understanding animal movement but has proven challenging to study. Advances in animal tracking technology, theoretical movement models and cognitive sciences have facilitated research in each of these fields, but also created a need for synthetic examination of the linkages between memory and animal movement. Here, we draw together research from several disciplines to understand the relationship between animal memory and movement processes. First, we frame the problem in terms of the characteristics, costs and benefits of memory as outlined in psychology and neuroscience. Next, we provide an overview of the theories and conceptual frameworks that have emerged from behavioural ecology and animal cognition. Third, we turn to movement ecology and summarise recent, rapid developments in the types and quantities of available movement data, and in the statistical measures applicable to such data. Fourth, we discuss the advantages and interrelationships of diverse modelling approaches that have been used to explore the memory–movement interface. Finally, we outline key research challenges for the memory and movement communities, focusing on data needs and mathematical and computational challenges. We conclude with a roadmap for future work in this area, outlining axes along which focused research should yield rapid progress.
The impact of an invasive plant changes over time
Authors: Dostál Petr , Müllerová Jana , Pyšek Petr , Pergl Jan , Klinerová Tereza
Published: August 2013

Many exotic plant invaders pose a serious threat to native communities, but little is known about the dynamics of their impacts over time. In this study, we explored the impact of an invasive plant Heracleum mantegazzianum (giant hogweed) at 24 grassland sites invaded for different periods of time (from 11 to 48 years). Native species' richness and productivity were initially reduced by hogweed invasion but tended to recover after ~30 years of hogweed residence at the sites. Hogweed cover declined over the whole period assessed. A complementary common garden experiment suggested that the dynamics observed in the field were due to a negative plant–soil feedback; hogweed survival and biomass, and its competitive ability were lower when growing in soil inocula collected from earlier‐invaded grasslands. Our results provide evidence that the initial dominance of an invasive plant species and its negative impact can later be reversed by stabilising processes.
Factors Affecting Geographic Variation in Echolocation Calls of the Endemic Myotis davidii in China
Authors: Jiang Tinglei , You Yuyan , Liu Sen , Lu Guanjun , Wang Lei , Wu Hui , Berquist Sean , Ho Jennifer , Puechmaille Sébastien J. , Feng Jiang
Published: August 2013

The sensory drive hypothesis of speciation predicts that divergence in communication systems will occur when environments differ and that this sensory divergence can ultimately promote speciation. The factors affecting geographic evolution in acoustic signals remain poorly understood, especially in the contexts of high gene flow. This study investigated variation patterns in peak frequency emitted by the Chinese endemic Myotis davidii on a broad geographic scale by evaluating the relative importance of morphological, environmental, geographic, and genetic variables. Significant variation in peak frequency was observed among regions, but peak frequencies among populations within region had some percentage of similarity. Differences in peak frequency were not associated with morphological difference, genetic structure, and geographic distance among regions, which suggested that peak frequency divergences in M. davidii were not the primary driver of regions' isolation in a context of weak gene flow. Within the Middle East Plain (MEP), one of the regions delineated in this study, peak frequency differences of M. davidii were not significantly correlated with genetic distance and geographic distance among populations, suggesting that peak frequency was not be subject to cultural drift within MEP. Our results provide evidence that geographic variation in echolocation call design may evolve as a consequence of local adaptation to climate conditions.
Unified correlation of in‐plane and out‐of‐plane constraints with fracture toughness
Authors: Yang J. , Wang G. Z. , Xuan F. Z. , Tu S. T.
Published: August 2013

In this paper, the specimens with different geometries and loading configurations were used to study the unified correlation of in‐plane and out‐of‐plane constraints with fracture toughness by using numerical simulation method. The results show that the unified constraint parameter Ap which was defined on the basis of the areas surrounded by the equivalent plastic strain isolines ahead of crack tip can characterise both in‐plane and out‐of‐plane constraints induced by different specimen geometries and loading configurations. A sole linear relation between the normalised fracture toughness JIC/Jref and was obtained. The JIC/Jref ‐ line is a unified correlation line of in‐plane and out‐of‐plane constraints with fracture toughness of a material, and the constraint dependent fracture toughness of a material can be determined from the unified correlation line. The results also demonstrate that the out‐of‐plane constraint effect is related to the in‐plane constraint effect, and there exists interaction between them. The higher in‐plane constraint strengthens the out‐of‐plane constraint effect, whereas the lower in‐plane constraint is not sensitive to the out‐of‐plane constraint effect.
Three‐dimensional effects in finite thickness plates weakened by rounded notches and holes under in‐plane shear
Authors: Berto F. , Marangon C.
Published: August 2013

It is well known that in cracked plates under in‐plane shear loading, an induced out‐of‐plane mode, due to the Poisson's effect, is automatically generated. Some recent studies have shown the importance of this coupled mode (called mode O) in plates weakened by sharp V‐notches characterized by different notch opening angles. Particular attention has been paid to the scale effect focusing also on the implications of the coupled mode to different material scale levels.

Also when the notch root radius is different from zero, the out‐of‐plane mode continues to exist, and its intensity with respect to the generating mode depends on the notch radius and the plate thickness. Aim of this paper is to discuss the main features of the out‐of‐plane mode dealing with three‐dimensional plates weakened by blunt notches. In particular, some results from blunt V‐notches, circular and elliptic holes are discussed in detail and presented here. The main key‐point highlighted in the present contribution is that always three‐dimensional effects exist in finite thickness plates, because mode I, II and III cannot exist in isolation. The importance of induced modes varies from case to case and depends on the geometry of the component and on the externally applied load. These effects cannot be neglected a priori even if, in some cases, they may be negligible.
Reappraising the effects of habitat structure on river macroinvertebrates
Authors: Barnes Jacqueline B. , Vaughan Ian P. , Ormerod Steve J.
Published: August 2013

Although rivers are highly structured physically, generalisations about the consequences for macroinvertebrates remain elusive. In part, this reflects the difficulty of quantifying structure per se as well as differentiating the effects on organisms of complexity (i.e. the total abundance of structural features), heterogeneity (i.e. the composition and spatial arrangement of different structural features) and surface area.

Three hypotheses about habitat structure were tested at the patch scale (<0.1 m2) in tributaries of the Rivers Wye and Usk, mid‐Wales (U.K.): (i) greater habitat heterogeneity and surface complexity alter macroinvertebrate assemblage composition and increase diversity, richness and abundance, (ii) the effects of complexity on macroinvertebrates are distinct from those of increased surface area, and (iii) habitat structure (heterogeneity and complexity) is a major determinant of variations in macroinvertebrates among habitat types (bedrock, silt, sand, gravel, pebbles and cobbles).

Surface complexity, described using fractal dimension, and surface area were estimated from ten riverbed profiles at 0.25 × 0.25 m locations sampled for macroinvertebrates. Habitat heterogeneity was determined within 1 m radii and described by principal components reflecting the patchiness of habitat mosaics (PC1) and the evenness of patch sizes (PC2). Relationships between these heterogeneity PCs, fractal dimension, surface area, habitat type and macroinvertebrates were analysed using models excluding and including habitat type. We also used hierarchical partitioning to investigate the variance explained independently and jointly by each of the variables.

Bedrock was the least complex habitat, whilst pebbles were the most complex. Habitat mosaics surrounding cobbles had the most variable patch sizes, whilst those around gravel or bedrock were the most even.

Complexity (but not heterogeneity) increased macroinvertebrate diversity and abundance independently of surface area, but independently accounted for <5% of the variation in macroinvertebrates. Complexity and surface area also independently increased taxonomic richness, but rarefaction showed that this was an artefact of increased abundances. Habitat type explained more of the variation (up to 21%) and rendered complexity and surface area redundant in our models. Bedrock, silt and sand typically had reduced diversity, richness and abundance of (mostly) Ephemeroptera, Plecoptera and Trichoptera, whilst silt had abundant Chironomidae.

These results support the first two hypotheses, but only in part. Habitat heterogeneity did not affect macroinvertebrates, whilst the effects of complexity were weak. The major implication is that habitat type affects macroinvertebrates through factors other than structure alone, and we advocate a wider reappraisal of the processes involved.
The role of SDF‐1 and CXCR4 on odontoblastic differentiation in human dental pulp cells
Authors: Kim D. S. , Kim Y. S. , Bae W. J. , Lee H. J. , Chang S. W. , Kim W. S. , Kim E. C.
Published: August 2013

Aim

To examine the role of stromal cell–derived factor 1 (SDF‐1) signalling during odontogenic differentiation in human dental pulp cells (HDPCs).

Methodology

Human dental pulp cells were treated with differentiation medium, recombinant human SDF‐1, neutralizing antibody for SDF‐1 or CXCR4, pertussis toxin (PTX) and AMD3100. The expression of SDF‐1 and its receptor chemokine receptor type 4 (CXCR4) was measured by reverse transcription–polymerase chain reaction (RT‐PCR) and Western blotting. Odontoblastic differentiation was determined using alkaline phosphatase (ALP) activity assay, mineralized nodule formation and marker mRNAs by RT‐PCR.

Results

Marked upregulation of SDF‐1 and CXCR4 mRNA and protein was observed in cells grown 7 days in osteogenic induction medium. The addition of recombinant human SDF‐1 to HDPCs significantly (P < 0.05) increased ALP activity, mineralized nodule formation and odontoblast marker mRNAs in a dose‐dependent manner. Blocking SDF‐1 signalling using antibodies against SDF‐1 or CXCR4, or the G‐protein‐coupled receptor inhibitor PTX, and CXCR4 inhibitor AMD3100, strongly suppressed induction of odontogenic differentiation in HDPCs.

Conclusions

Odontoblastic differentiation was stimulated by SDF‐1 activation and repressed by SDF‐1/CXCR4 inhibition. Thus, SDF‐1/CXCR4 signalling may be a new therapeutic target and strategy to promote repair and regeneration in endodontics.
Role of regulatory T cells during virus infection
Authors: Veiga‐Parga Tamara , Sehrawat Sharvan , Rouse Barry T.
Published: August 2013

The host response to viruses includes multiple cell types that have regulatory function. Most information focuses on CD4+ regulatory T cells that express the transcription factor Foxp3+ (Tregs), which are the topic of this review. We explain how viruses through specific and non‐specific means can trigger the response of thymus‐derived natural Tregs as well as induce Tregs. The latter derive under appropriate stimulation conditions either from uncommitted precursors or from differentiated cells that convert to become Tregs. We describe instances where Tregs appear to limit the efficacy of antiviral protective immunity and other, perhaps more common, immune‐mediated inflammatory conditions, where the Tregs function to limit the extent of tissue damage that occurs during a virus infection. We discuss the controversial roles that Tregs may play in the pathogenesis of human immunodeficiency and hepatitis C virus infections. The issue of plasticity is discussed, as this may result in Tregs losing their protective function when present in inflammatory environments. Finally, we mention approaches used to manipulate Treg numbers and function and assess their current value and likely future success to manage the outcome of virus infection, especially those that are responsible for chronic tissue damage.
The contextual role of TNFR family members in CD8+ T‐cell control of viral infections
Authors: Wortzman Michael E. , Clouthier Derek L. , McPherson Ann J. , Lin Gloria H. Y. , Watts Tania H.
Published: August 2013

Immunity to viruses must be tightly controlled to avoid pathology. Receptors and ligands of the tumor necrosis factor (TNF) family play important roles in controlling lymphocyte activation and survival during an immune response. The role of specific TNF receptor (TNFR) family members in antiviral immunity depends on the stage of the immune response and can vary with the virus type and its virulence. Here, we focus on five members of the TNFR family that are prominently expressed on CD8+ T cells during viral infections, namely, 4‐1BB (CD137), CD27, OX40 (CD134), GITR, and TNFR2. 4‐1BB, CD27, OX40, and GITR have primarily prosurvival roles for CD8+ T cells during viral infection, although under some circumstances 4‐1BB, GITR, or CD27 signals can limit immunity. Although TNFR2 can be costimulatory under some circumstances, its main role in CD8+ T‐cell responses during viral infection appears to be in contraction of the response. Several TNF family ligands are being explored as adjuvants for viral vaccines, and agonistic antibodies to TNFR family members are being investigated for immunotherapy of chronic viral infection alone and in combination with checkpoint blockade. Such therapies will require thorough and specific optimization to avoid pathology induced by hyperstimulation of these pathways.
The expanding role of NLRs in antiviral immunity
Authors: Lupfer Christopher , Kanneganti Thirumala‐Devi
Published: August 2013

Nucleotide oligomerization and binding domain (NOD)‐like receptors (NLRs) are a major constituent of the cytosolic innate immune‐sensing machinery and participate in a wide array of pathways including nuclear factor κB (NF‐κB), mitogen‐activated protein kinase (MAPK), inflammasome, and type I interferon (IFN) signaling. NLRs have known roles in autoimmune, autoinflammatory, and infectious diseases. With respect to virus infection, NLRP3 is the most extensively studied NLR, including mechanisms of activation and inhibition. Furthermore, the importance of NLRP3 in both innate and adaptive immunity has been demonstrated. In comparison to NLRP3, the roles of other NLRs during virus infection are only just emerging. NLRC2 is an important activator of innate antiviral signaling and was recently found to mitigate inflammation during virus infection through autophagy. Finally, functions for NLRX1 in immune modulation and reactive oxygen species production require further examination and the importance of NLRC5 as a transactivator of major histocompatibility complex (MHC) class I and antigen presentation is currently developing. In this review, we discuss current knowledge pertaining to viruses and NLRs as well as areas of potential research, which will help advance the study of NLR biology during virus infection.
Bugs in the system
Authors: Menachery Vineet D. , Baric Ralph S.
Published: August 2013

Immunity to respiratory virus infection is governed by complex biological networks that influence disease progression and pathogenesis. Systems biology provides an opportunity to explore and understand these multifaceted interactions based on integration and modeling of multiple biological parameters. In this review, we describe new and refined systems‐based approaches used to model, identify, and validate novel targets within complex networks following influenza and coronavirus infection. In addition, we propose avenues for extension and expansion that can revolutionize our understanding of infectious disease processes. Together, we hope to provide a window into the unique and expansive opportunity presented by systems biology to understand complex disease processes within the context of infectious diseases.
The great balancing act: regulation and fate of antiviral T‐cell interactions
Authors: Moseman E. Ashley , McGavern Dorian B.
Published: August 2013

The fate of T lymphocytes revolves around a continuous stream of interactions between the T‐cell receptor (TCR) and peptide‐major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of T‐cell subsets. The cellular context of T‐cell engagement with antigen‐presenting cells, either in lymphoid or non‐lymphoid tissues, plays an important role in determining how these cells respond to antigen encounters. CD8+ T cells are essential for clearance of a lymphocytic choriomeningitis virus (LCMV) infection, but the virus can present a number of unique challenges that antiviral T cells must overcome. Peripheral LCMV infection can lead to rapid cytolytic clearance or chronic viral persistence; central nervous system infection can result in T‐cell‐dependent fatal meningitis or an asymptomatic carrier state amenable to immunotherapeutic clearance. These diverse outcomes all depend on interactions that require TCR engagement of cognate peptide‐MHC complexes. In this review, we explore the diversity in antiviral T‐cell behaviors resulting from TCR engagement, beginning with an overview of the immunological synapse and progressing to regulators of TCR signaling that shape the delicate balance between immunopathology and viral clearance.
The impact of macroautophagy on CD8+ T‐cell‐mediated antiviral immunity
Authors: Perot Brieuc P. , Ingersoll Molly A. , Albert Matthew L.
Published: August 2013

Macroautophagy is a catabolic recycling pathway, which can be induced by various stress stimuli. Viruses are able to manipulate autophagy in the cells that they infect. The impact of autophagy on the innate immune response to viruses and its stimulatory role in antigen presentation to CD4+ T cells are well documented. Herein, we present the impact of autophagy on the activation of cytotoxic T lymphocyte (CTL)‐mediated antiviral immune responses, which are required for the eradication or control of multiple viruses. We first discuss the general mechanisms by which viruses can either induce or block autophagy in cells. We then explore the cross‐talk between autophagy and innate immune processes, which are both first line defenses against viruses; and constitute crucial steps for the initiation of potent adaptive immune responses. We describe the impact of autophagy on the presentation of viral peptide antigens on class I major histocompatibility complex (MHC I), a prerequisite for the priming of CTL responses. In sum, our review highlights the interplay between viruses and three integrated host response pathways – autophagy, innate and adaptive immunity – providing a framework for future mechanistic and pathogenesis‐based research.
Geographical variation in hurricane impacts among sea turtle populations
Authors: Dewald Julius R. , Pike David A.
Published: August 2013

Aim

Hurricanes bring wind and rainfall that can have dramatic effects on coastal ecosystems, which provide important nesting locations for some migratory species. We investigated the frequency with which hurricanes impact spatially and biologically distinct sea turtle nesting populations to understand whether the reproductive biology of sea turtles can buffer population‐level impacts of these disturbances.

Location

North‐western Atlantic and north‐eastern Pacific Oceans.

Methods

Historical hurricane paths from 1970 to 2007 were combined into a spatial layer of seasonal storm frequency, which we used to quantify the frequency of impacts on sea turtle nesting sites. This was done by comparing spatio‐temporal patterns of hurricane frequency among nesting sites used by different species and spatially/biologically distinct populations (‘regional management units’).

Results

Hurricanes affected 97% of sea turtle nesting beaches (n = 2444) over four decades, and the seasonal incidence of these storms overlapped substantially with sea turtle nesting and egg incubation periods. The spatial distribution of storms, in relation to the distribution of species and regional management units, determined relative exposure to large storm events. Green (Chelonia mydas), hawksbill (Eretmochelys imbricata) and leatherback (Dermochelys coriacea) turtle nesting beaches experienced relatively frequent storms; loggerhead (Caretta caretta) and Kemp's ridley (Lepidochelys kempii) turtle nesting beaches experienced relatively fewer storms; and olive ridley turtle (Lepidochelys olivacea) nesting sites were least affected.

Main conclusions

Extreme weather events are common features of coastal environments and may impact sea turtles by altering nesting habitat quality (through sand erosion and accretion) and lowering within‐season reproductive success by drowning incubating embryos or eroding nests. The unique reproductive attributes of sea turtles (i.e. individual females reproduce at 2–5‐year intervals, and when reproducing lay 2–7 clutches of c. 100 large eggs at c. 2‐week intervals) may be uniquely suited to exploiting highly disturbed nesting habitats. The impacts of hurricanes on sea turtle populations may be limited because even in severe storm seasons only a proportion of adult females are reproducing, and only those eggs incubating at the time of storm impact will be directly affected. Understanding whether the frequency of large storms influences long‐term population dynamics will aid in the development of effective local and regional management plans for sea turtle recovery efforts.
Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro
Authors: Wen Jiadi , Zhu Hua , Leung Peter C.K.
Published: August 2013

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS‐1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β‐estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS‐4, ‐5, ‐8 or ‐9 expression in human endometrial stromal cells in vitro. Real‐time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS‐8, ‐9 and ‐5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4‐ or DHT‐mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization.
Periodontal disease and oral health‐related behavior as factors associated with preterm birth: a case–control study in south‐eastern Brazil
Authors: Macedo J. F. , Ribeiro R. A. , Machado F. C. , Assis N. M. S. P. , Alves R. T. , Oliveira A. S. , Ribeiro L. C.
Published: August 2013

Background and Objective

Several studies have suggested a link between periodontal disease and preterm birth, but the mechanism of how this occurs remains controversial. Therefore, this study aimed to investigate whether periodontal disease, defined according to two commonly used clinical definitions, is associated with preterm birth and to examine the association regarding oral health‐related behaviors during pregnancy.

Material and Methods

This case–control study included women 18–40 years of age. Demographic and socio‐economic data, information on current and previous pregnancies, and data on dental health‐related behaviors and periodontal clinical parameters were collected within 48 h postpartum. Periodontal disease was assessed according to two definitions: four or more teeth with at least one site showing a probing depth of ≥ 4 mm and clinical attachment level of ≥ 3 mm (Definition 1); or at least one site with probing depth and clinical attachment level of ≥ 4 mm (Definition 2). The chi‐square test was used to examine differences in the proportion of categorical variables. Bivariate analysis was performed to analyze the proportion of preterm births with respect to independent variables. Multiple logistic regression analyses were used to assess the association between periodontal disease and preterm birth. Odds ratios (ORs) were calculated with a 95% confidence interval (95% CI).

Results

A total of 296 postpartum women met the inclusion criteria. The case group included 74 women who delivered a preterm neonate (< 37 wk of gestation) and the control group included 222 women with deliveries at term (≥ 37 wk). Periodontal disease according to Definition 1 was not associated with fewer weeks of gestation (adjusted OR (ORadjusted) = 1.62; 95% CI = 0.80–3.29; p = 0.178). However, a significant association was found between periodontal disease, according to Definition 2, and preterm birth (ORadjusted = 1.98; 95% CI = 1.14–3.43; p = 0.015). Increased appetite and a low number of daily toothbrushings were associated with preterm birth, regardless of the definition of periodontal disease used.

Conclusion

Periodontal disease defined according to Definition 2 and unfavorable oral health‐related behavior were factors associated with preterm birth.
The Effects of Video Self‐Modeling on the Decoding Skills of Children at Risk for Reading Disabilities
Authors: Ayala Sandra M. , O'Connor Rollanda
Published: August 2013

Ten first grade students who had responded poorly to a Tier 2 reading intervention in a response to intervention (RTI) model received an intervention of video self‐modeling to improve decoding skills and sight word recognition. Students were video recorded blending and segmenting decodable words and reading sight words. Videos were edited and viewed a minimum of four times per week. Data were collected twice per week using curriculum‐based measures. A single subject multiple baseline across participants design was used. Results indicated an increase in decoding skills and sight word recognition for all participants. A 2‐week posttest maintenance assessment showed retention or increases for 70 percent of participants. Results from the study offer promise for a specific intervention that may reach particular students who respond poorly to Tier 2 reading instruction.
Special Education in a 4‐Year Response to Intervention (RtI) Environment: Characteristics of Students with Learning Disability and Grade of Identification
Authors: O'Connor Rollanda E. , Bocian Kathleen M. , Beach Kristen D. , Sanchez Victoria , Flynn Lindsay J.
Published: August 2013

This 4‐year longitudinal research was designed to study special education determinations of students who participated in Tier 2 intervention in a Response to Intervention (RtI) model focused on reading across Grades 1–4. We compared identification rates for learning disabilities (LD) and student characteristics of 381 students the year prior to implementation with 377 students in the RtI environment. Across schools, 38–60 percent of students were English language learners (ELL). Key outcomes by Grade 4 for students with LD who had participated in a model of RtI were relatively greater reading impairment with effect sizes ranging from 0.64 to 0.82, and more equitable representation across ELL and native English speakers than in the cohort prior to RtI implementation. Notably, one‐third of the students identified for special services as LD in these schools were not identified until 4th grade.
Accurately Predicting Future Reading Difficulty for Bilingual Latino Children at Risk for Language Impairment
Authors: Petersen Douglas B. , Gillam Ronald B.
Published: August 2013

Sixty‐three bilingual Latino children who were at risk for language impairment were administered reading‐related measures in English and Spanish (letter identification, phonological awareness, rapid automatized naming, and sentence repetition) and descriptive measures including English language proficiency (ELP), language ability (LA), socioeconomic status, and preschool attendance at kindergarten. At the end of first grade, English word‐level reading and reading comprehension (RC) were measured. Results indicated that the Spanish predictor measures did not account for significant variance over and above the English predictor measures for any of the first‐grade outcome measures. Of the descriptive predictor measures, only ELP and LA were significantly predictive, accounting for unique variance in first‐grade RC. Sensitivity ranged from .67 to .86 and specificity ranged from .82 to .93 across the four first‐grade outcome measures.
The Science of the Individual
Authors: Rose L. Todd , Rouhani Parisa , Fischer Kurt W.
Published: August 2013

Our goal is to establish a science of the individual, grounded in dynamic systems, and focused on the analysis of individual variability. Our argument is that individuals behave, learn, and develop in distinctive ways, showing patterns of variability that are not captured by models based on statistical averages. As such, any meaningful attempt to develop a science of the individual necessarily begins with an account of the individual variability that is pervasive in all aspects of behavior, and at all levels of analysis. Using examples from fields as diverse as education and medicine, we show how starting with individual variability, not statistical averages, helped researchers discover two sources of ordered variability—pathways and contexts—that have implications for theory, research, and practice in multiple disciplines. We conclude by discussing three broad challenges—data, models, and the nature of science—that must be addressed to ensure that the science of the individual reaches its full potential.
I. NIH TOOLBOX COGNITION BATTERY (CB): INTRODUCTION AND PEDIATRIC DATA
Authors: Weintraub Sandra , Bauer Patricia J. , Zelazo Philip David , Wallner‐Allen Kathleen , Dikmen Sureyya S. , Heaton Robert K. , Tulsky David S. , Slotkin Jerry , Blitz David L. , Carlozzi Noelle E. , Havlik Richard J. , Beaumont Jennifer L. , Mungas Dan , Manly Jennifer J. , Borosh Beth G. , Nowinski Cindy J. , Gershon Richard C.
Published: August 2013

This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience‐related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large‐scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3–15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2–6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age.
II. NIH TOOLBOX COGNITION BATTERY (CB): MEASURING EXECUTIVE FUNCTION AND ATTENTION
Authors: Zelazo Philip David , Anderson Jacob E. , Richler Jennifer , Wallner‐Allen Kathleen , Beaumont Jennifer L. , Weintraub Sandra
Published: August 2013

In this chapter, we discuss two measures designed to assess executive function (EF) as part of the NIH Toolbox Cognition Battery (CB) and report pediatric data from the validation study. EF refers to the goal‐directed cognitive control of thought, action, and emotion. Two measures were adapted for standardized computer administration: the Dimensional Change Card Sort (a measure of cognitive flexibility) and a flanker task (a measure of inhibitory control in the context of selective visual attention). Results reveal excellent developmental sensitivity across childhood, excellent reliability, and (in most cases) excellent convergent validity. Correlations between the new NIH Toolbox measures and age were higher for younger children (3–6 years) than for older children (8–15 years), and evidence of increasing differentiation of EF from other aspects of cognition (indexed by receptive vocabulary) was obtained.