bluuebunny/crossref_metadata_2025 huggingface dataset:
Diachronous beginnings of the Anthropocene: The lower bounding surface of anthropogenic deposits
Authors: Edgeworth Matt , deB Richter Dan , Waters Colin , Haff Peter , Neal Cath , Price Simon James
Published: January 2015

Across a large proportion of Earth’s ice-free land surfaces, a solid-phase stratigraphic boundary marks the division between humanly modified ground and natural geological deposits. At its clearest, the division takes the form of an abrupt surface at the base of deposits variously called ‘artificial ground’, ‘anthropogenic ground’ or ‘archaeological stratigraphy’ – which together comprise a distinctive part of the geosphere called the ‘archaeosphere’. In other cases the bounding surface is more diffuse, gradational or mixed, due to action of non-human agencies and anthropedogenic forcings. It is alternately conformable and unconformable. Layers above typically contain artificial features, structures, artifacts and other material traces of human activity, in contrast to their relative absence in layers below. A fundamental characteristic of the boundary is that it is diachronous, still being formed and renewed today. In examining the boundary, this paper asks – does it reflect the diachronous onset and development of the Anthropocene itself?
Knowledge of and Attitudes Toward ADHD Among Teachers
Authors: Youssef Marsha K. , Hutchinson Gerard , Youssef Farid F.
Published: January 2015

Teachers are often the first persons responsible for identifying children with attention deficit hyperactivity disorder (ADHD) and are increasingly being called on to help manage such children. We sought to assess teachers’ knowledge of and attitudes toward ADHD in Trinidad & Tobago, a small island developing state in the Caribbean region. Based on previously published work, an instrument was adapted and pilot tested. Using convenience sampling, 440 questionnaires were distributed and 277 valid questionnaires were returned (response rate, 63%). Total knowledge scores were low, mean 12.6/26. Both postgraduate education and in-service training significantly improved knowledge scores as did having previously taught a child with ADHD. Attitudes toward children with ADHD were generally positive although most teachers felt children with ADHD should be taught by specialist teachers. Results suggest greater efforts must be made to provide teacher training specifically in the identification and management of children with ADHD.
Ultrasonically assisted friction stir welding of aluminium alloy 6061
Authors: Ma H. K. , He D. Q. , Liu J. S.
Published: January 2015

Ultrasonically assisted friction stir welding (UAFSW) was explored. Metallographic structures and material flow prepared by UAFSW were compared with those prepared by conventional FSW. Hardness curves, tensile strength, and elongation of welds fabricated at different ultrasonic powers were characterised. Experimental results showed that hardness curves, tensile strength of welds increased with increased ultrasonic power when it was less than 50%. The elongations decreased with ultrasonic energy output increased. Scanning electron microscopy photographs in different positions of fracture by UAFSW show fracture pattern and origin.
Dry rolling/sliding wear of nanostructured pearlite
Authors: Das Bakshi S. , Leiro A. , Prakash B. , Bhadeshia H. K. D. H.
Published: January 2015

The dry rolling–sliding wear behaviour of pearlite that has an interlamellar spacing of just 85 nm has been characterised. Its wear resistance is found to be comparable to that of much harder bainitic steels. Microstructural observations indicate that there is substantial plastic deformation of both ferrite and cementite components of pearlite in the vicinity of the wear surface. Plasticity is not expected from Hertzian analysis that assumes a smooth contact surface. Instead, it is likely to be a consequence of exaggerated stresses due to surface roughness. The material remains ductile to shear strains in the order of 4. Diffraction data indicate that the coherent domain size is reduced to about half the interlamellar spacing and that some of the cementite may dissolve and contribute to the expansion of the lattice parameter of ferrite.
shRNA library screening identifies nucleocytoplasmic transport as a mediator of BCR-ABL1 kinase-independent resistance
Authors: Khorashad Jamshid S. , Eiring Anna M. , Mason Clinton C. , Gantz Kevin C. , Bowler Amber D. , Redwine Hannah M. , Yu Fan , Kraft Ira L. , Pomicter Anthony D. , Reynolds Kimberly R. , Iovino Anthony J. , Zabriskie Matthew S. , Heaton William L. , Tantravahi Srinivas K. , Kauffman Michael , Shacham Sharon , Chenchik Alex , Bonneau Kyle , Ullman Katharine S. , O’Hare Thomas , Deininger Michael W.
Published: January 2015

Key Points

A function-first shRNA library screen identifies pathways involved in BCR-ABL1 kinase-independent TKI resistance. RAN or XPO1 inhibition impairs survival of progenitors from newly diagnosed or TKI-resistant CML patients.
MRTF-SRF signaling is required for seeding of HSC/Ps in bone marrow during development
Authors: Costello Patrick , Sargent Mathew , Maurice Diane , Esnault Cyril , Foster Katie , Anjos-Afonso Fernando , Treisman Richard
Published: January 2015

Key Points

Inactivation of either Srf or both Mrtfs in HSC/Ps prevents their colonization of the bone marrow. HSC/Ps lacking functional Srf or both Mrtfs exhibit greatly reduced chemotactic response to SDF-1.
Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression
Authors: Jacobsen Eric D. , Sharman Jeff P. , Oki Yasuhiro , Advani Ranjana H. , Winter Jane N. , Bello Celeste M. , Spitzer Gary , Palanca-Wessels Maria Corinna , Kennedy Dana A. , Levine Pamela , Yang Jing , Bartlett Nancy L.
Published: January 2015

Key Points

Brentuximab vedotin was active in DLBCL across a range of CD30 expression levels, and objective responses occurred in 44% of patients.
Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib
Authors: Jain Preetesh , Keating Michael , Wierda William , Estrov Zeev , Ferrajoli Alessandra , Jain Nitin , George Binsah , James Danelle , Kantarjian Hagop , Burger Jan , O’Brien Susan
Published: January 2015

Key Points

Clinical characteristics, causes of discontinuation, and outcome of patients who progress or fail ibrutinib are described. Patients with CLL who progress early on ibrutinib therapy have poor outcomes.
Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21
Authors: Caescu Cristina I. , Guo Xingyi , Tesfa Lydia , Bhagat Tushar D. , Verma Amit , Zheng Deyou , Stanley E. Richard
Published: January 2015

Key Points

Analysis of CSF-1R pTyr-regulated messenger RNAs identifies novel signaling nodes and networks that can be targeted to modulate macrophage functions. miR-21 is a novel CSF-1R pTyr-721–induced molecule that suppresses the macrophage M1 phenotype and enhances the M2 phenotype.
Effect of obstructive sleep apnoea on severity and short-term prognosis of acute coronary syndrome
Authors: Barbé Ferran , Sánchez-de-la-Torre Alicia , Abad Jorge , Durán-Cantolla Joaquin , Mediano Olga , Amilibia Jose , Masdeu Maria José , Florés Marina , Barceló Antonia , de la Peña Mónica , Aldomá Albina , Worner Fernando , Valls Joan , Castellà Gerard , Sánchez-de-la-Torre Manuel
Published: January 2015

The goal of this study was to evaluate the influence of obstructive sleep apnoea on the severity and short-term prognosis of patients admitted for acute coronary syndrome.

Obstructive sleep apnoea was defined as an apnoea–hypopnoea index (AHI) >15 h−1. We evaluated the acute coronary syndrome severity (ejection fraction, Killip class, number of diseased vessels, and plasma peak troponin) and short-term prognosis (length of hospitalisation, complications and mortality).

We included 213 patients with obstructive sleep apnoea (mean±sdAHI 30±14 h−1, 61±10 years, 80% males) and 218 controls (AHI 6±4 h−1, 57±12 years, 82% males). Patients with obstructive sleep apnoea exhibited a higher prevalence of systemic hypertension (55%versus37%, p<0.001), higher body mass index (29±4 kg·m−2versus26±4 kg·m−2, p<0.001), and lower percentage of smokers (61%versus71%, p=0.04). After adjusting for smoking, age, body mass index and hypertension, the plasma peak troponin levels were significantly elevated in the obstructive sleep apnoea group (831±908 ng·L−1versus987±884 ng·L−1, p=0.03) and higher AHI severity was associated with an increased number of diseased vessels (p=0.04). The mean length of stay in the coronary care unit was higher in the obstructive sleep apnoea group (p=0.03).

This study indicates that obstructive sleep apnoea is related to an increase in the peak plasma troponin levels, number of diseased vessels, and length of stay in the coronary care unit.
Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes
Authors: Taccone Fabio Silvio , Van den Abeele Anne-Marie , Bulpa Pierre , Misset Benoit , Meersseman Wouter , Cardoso Teresa , Paiva José-Artur , Blasco-Navalpotro Miguel , De Laere Emmanuel , Dimopoulos George , Rello Jordi , Vogelaers Dirk , Blot Stijn I ,   on behalf of the AspICU Study Investigators
Published: January 2015

Introduction

Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.

Methods

An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation.

Results

A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis.

Conclusions

IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.
Optimal site for ultrasound-guided venous catheterisation in paediatric patients: an observational study to investigate predictors for catheterisation success and a randomised controlled study to determine the most successful site
Authors: Takeshita Jun , Nakayama Yoshinobu , Nakajima Yasufumi , Sessler Daniel I , Ogawa Satoru , Sawa Teiji , Mizobe Toshiki
Published: January 2015

Introduction

Venous catheterisation in paediatric patients can be technically challenging. We examined factors affecting catheterisation of invisible and impalpable peripheral veins in children and evaluated the best site for ultrasound-guided catheterisation.

Methods

Systolic pressure, age, sex, and American Society of Anaesthesiologists (ASA) physical status were determined in 96 children weighing less than 20 kg. Vein diameter and subcutaneous depth were measured with ultrasound. Logistic regression was used to evaluate the contribution of these factors to cannulation success with (n = 65) or without (n = 31) ultrasound guidance. Thereafter, we randomly assigned 196 patients for venous catheter insertion in the dorsal veins of the hand, the cephalic vein in the forearm, or the great saphenous vein. Success rates and vein diameters were evaluated by using Dunn tests; insertion time was evaluated by using Kaplan-Meier cumulative incidence analysis.

Results

Independent predictors of catheterisation were ultrasound guidance (odds ratio (OR) = 7.3, 95% confidence interval (CI) 2.0 to 26.0, P = 0.002), vein diameter (OR = 1.5 per 0.1 mm increase in diameter, 95% CI 1.1 to 2.0, P = 0.007), and ASA physical status (OR = 0.4 per status 1 increase, 95% CI 0.2 to 0.9, P = 0.03). Cephalic veins were significantly larger (cephalic diameter 1.8 mm, P = 0.001 versus saphenous 1.5 mm, P <0.001 versus dorsal 1.5 mm). Catheterisation success rates were significantly better at the cephalic vein than either the dorsal hand or saphenous vein (cephalic 95%, 95% CI 89% to 100%, P <0.001 versus dorsal 69%, 95% CI 56% to 82%, P = 0.03 versus saphenous 75%, 95% CI 64% to 86%).

Conclusions

The cephalic vein in the proximal forearm appears to be the most appropriate initial site for ultrasound-guided catheterisation in invisible and impalpable veins of paediatric patients.

Trial registry number

UMIN Clinical Trials Registry as UMIN000010961. Registered on 14 June 2013.
Neurokinin B Is Critical for Normal Timing of Sexual Maturation but Dispensable for Adult Reproductive Function in Female Mice
Authors: True Cadence , Nasrin Alam Sayeda , Cox Kimberly , Chan Yee-Ming , Seminara Stephanie B.
Published: January 2015

Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of pubertal development than adult reproductive function. NKB receptor-deficient mice are hypogonadotropic but have no defects in the timing of sexual maturation. The current study has performed the first phenotypic evaluation of mice bearing mutations in Tac2, the gene encoding the NKB ligand, to determine whether they have impaired sexual development similar to their human counterparts. Male Tac2−/− mice showed no difference in the timing of sexual maturation or fertility compared with wild-type littermates and were fertile. In contrast, Tac2−/− females had profound delays in sexual maturation, with time to vaginal opening and first estrus occurring significantly later than controls, and initial abnormalities in estrous cycles. However, cycling recovered in adulthood and Tac2−/− females were fertile, although they produced fewer pups per litter. Thus, female Tac2−/− mice parallel humans harboring NKB pathway mutations, with delayed sexual maturation and activation of the reproductive cascade later in life. Moreover, direct comparison of NKB ligand and receptor-deficient females confirmed that only NKB ligand-deficient animals have delayed sexual maturation, suggesting that in the absence of the NKB receptor, NKB may regulate the timing of sexual maturation through other tachykinin receptors.
Proper migration and axon outgrowth of zebrafish cranial motoneuron subpopulations require the cell adhesion molecule MDGA2A
Authors: Ingold Esther , vom Berg-Maurer Colette M. , Burckhardt Christoph J. , Lehnherr André , Rieder Philip , Keller Philip J. , Stelzer Ernst H. , Greber Urs F. , Neuhauss Stephan C. F. , Gesemann Matthias
Published: January 2015

The formation of functional neuronal circuits relies on accurate migration and proper axonal outgrowth of neuronal precursors. On the route to their targets migrating cells and growing axons depend on both, directional information from neurotropic cues and adhesive interactions mediated via extracellular matrix molecules or neighbouring cells. The inactivation of guidance cues or the interference with cell adhesion can cause severe defects in neuronal migration and axon guidance. In this study we have analyzed the function of the MAM domain containing glycosylphosphatidylinositol anchor 2A (MDGA2A) protein in zebrafish cranial motoneuron development. MDGA2A is prominently expressed in distinct clusters of cranial motoneurons, especially in the ones of the trigeminal and facial nerves. Analyses of MDGA2A knockdown embryos by light sheet and confocal microscopy revealed impaired migration and aberrant axonal outgrowth of these neurons; suggesting that adhesive interactions mediated by MDGA2A are required for the proper arrangement and outgrowth of cranial motoneuron subtypes.
Modelling of soldier fly halteres for gyroscopic oscillations
Authors: Parween Rizuwana , Pratap Rudra
Published: January 2015

Nature has evolved a beautiful design for small-scale vibratory rate-gyro in the form of dipteran halteres that detect body rotations via Coriolis acceleration. In most Diptera, including soldier fly, Hermetia illucens, halteres are a pair of special organs, located in the space between the thorax and the abdomen. The halteres along with their connecting joint with the fly's body constitute a mechanism that is used for muscle-actuated oscillations of the halteres along the actuation direction. These oscillations lead to bending vibrations in the sensing direction (out of the haltere's actuation plane) upon any impressed rotation due to the resulting Coriolis force. This induced vibration is sensed by the sensory organs at the base of the haltere in order to determine the rate of rotation. In this study, we evaluate the boundary conditions and the stiffness of the anesthetized halteres along the actuation and the sensing direction. We take several cross-sectional SEM (scanning electron microscope) images of the soldier fly haltere and construct its three dimensional model to get the mass properties. Based on these measurements, we estimate the natural frequency along both actuation and sensing directions, propose a finite element model of the haltere's joint mechanism, and discuss the significance of the haltere's asymmetric cross-section. The estimated natural frequency along the actuation direction is within the range of the haltere's flapping frequency. However, the natural frequency along the sensing direction is roughly double the haltere's flapping frequency that provides a large bandwidth for sensing the rate of rotation to the soldier flies.
Plant germline formation: common concepts and developmental flexibility in sexual and asexual reproduction
Authors: Schmidt Anja , Schmid Marc W. , Grossniklaus Ueli
Published: January 2015

The life cycle of flowering plants alternates between two heteromorphic generations: a diploid sporophytic generation and a haploid gametophytic generation. During the development of the plant reproductive lineages – the germlines – typically, single sporophytic (somatic) cells in the flower become committed to undergo meiosis. The resulting spores subsequently develop into highly polarized and differentiated haploid gametophytes that harbour the gametes. Recent studies have provided insights into the genetic basis and regulatory programs underlying cell specification and the acquisition of reproductive fate during both sexual reproduction and asexual (apomictic) reproduction. As we review here, these recent advances emphasize the importance of transcriptional, translational and post-transcriptional regulation, and the role of epigenetic regulatory pathways and hormonal activity.
Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes via repression of Sox9
Authors: Zhou Guangdi , Jiang Xuchao , Zhang Hai , Lu Yinzhong , Liu Anjun , Ma Xianhua , Yang Guan , Yang Rui , Shen Hongxing , Zheng Jianming , Hu Yiping , Yang Xiao , Zhang Weiping J. , Xie Zhifang
Published: January 2015

The terminal differentiation of hypertrophic chondrocytes is a tightly regulated process that plays a pivotal role in endochondral ossification. As a negative regulator, Sox9 is essentially downregulated in terminally differentiated hypertrophic chondrocytes. However, the underlying mechanism of Sox9 silencing is undefined. Here we show that the zinc finger protein Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes by repressing Sox9. In the developing skeleton of the mouse, Zbtb20 protein is highly expressed by hypertrophic chondrocytes from late embryonic stages. To determine its physiological role in endochondral ossification, we have generated chondrocyte-specific Zbtb20 knockout mice and demonstrate that disruption of Zbtb20 in chondrocytes results in delayed endochondral ossification and postnatal growth retardation. Zbtb20 deficiency caused a delay in cartilage vascularization and an expansion of the hypertrophic zone owing to reduced expression of Vegfa in the hypertrophic zone. Interestingly, Sox9, a direct suppressor of Vegfa expression, was ectopically upregulated at both mRNA and protein levels in the late Zbtb20-deficient hypertrophic zone. Furthermore, knockdown of Sox9 greatly increased Vegfa expression in Zbtb20-deficient hypertrophic chondrocytes. Our findings point to Zbtb20 as a crucial regulator governing the terminal differentiation of hypertrophic chondrocytes at least partially through repression of Sox9.
Microtubule-dependent apical restriction of recycling endosomes sustains adherens junctions during morphogenesis of the Drosophila tracheal system
Authors: Le Droguen Pierre-Marie , Claret Sandra , Guichet Antoine , Brodu Véronique
Published: January 2015

Epithelial remodelling is an essential mechanism for organogenesis, during which cells change shape and position while maintaining contact with each other. Adherens junctions (AJs) mediate stable intercellular cohesion but must be actively reorganised to allow morphogenesis. Vesicle trafficking and the microtubule (MT) cytoskeleton contribute to regulating AJs but their interrelationship remains elusive. We carried out a detailed analysis of the role of MTs in cell remodelling during formation of the tracheal system in the Drosophila embryo. Induction of MT depolymerisation specifically in tracheal cells shows that MTs are essential during a specific time frame of tracheal cell elongation while the branch extends. In the absence of MTs, one tracheal cell per branch overelongates, ultimately leading to branch break. Three-dimensional quantifications revealed that MTs are crucial to sustain E-Cadherin (Shotgun) and Par-3 (Bazooka) levels at AJs. Maintaining E-Cadherin/Par-3 levels at the apical domain requires de novo synthesis rather than internalisation and recycling from and to the apical plasma membrane. However, apical targeting of E-Cadherin and Par-3 requires functional recycling endosomes, suggesting an intermediate role for this compartment in targeting de novo synthesized E-Cadherin to the plasma membrane. We demonstrate that apical enrichment of recycling endosomes is dependent on the MT motor Dynein and essential for the function of this vesicular compartment. In addition, we establish that E-Cadherin dynamics and MT requirement differ in remodelling tracheal cells versus planar epithelial cells. Altogether, our results uncover an MT-Dynein-dependent apical restriction of recycling endosomes that controls adhesion by sustaining Par-3 and E-Cadherin levels at AJs during morphogenesis.
Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in theC. elegansgerm line
Authors: Gupta Pratyush , Leahul Lindsay , Wang Xin , Wang Chris , Bakos Brendan , Jasper Katie , Hansen Dave
Published: January 2015

The level of stem cell proliferation must be tightly controlled for proper development and tissue homeostasis. Multiple levels of gene regulation are often employed to regulate stem cell proliferation to ensure that the amount of proliferation is aligned with the needs of the tissue. Here we focus on proteasome-mediated protein degradation as a means of regulating the activities of proteins involved in controlling the stem cell proliferative fate in the C. elegans germ line. We identify five potential E3 ubiquitin ligases, including the RFP-1 RING finger protein, as being involved in regulating proliferative fate. RFP-1 binds to MRG-1, a homologue of the mammalian chromodomain-containing protein MRG15 (MORF4L1), which has been implicated in promoting the proliferation of neural precursor cells. We find that C. elegans with reduced proteasome activity, or that lack RFP-1 expression, have increased levels of MRG-1 and a shift towards increased proliferation in sensitized genetic backgrounds. Likewise, reduction of MRG-1 partially suppresses stem cell overproliferation. MRG-1 levels are controlled independently of the spatially regulated GLP-1/Notch signalling pathway, which is the primary signal controlling the extent of stem cell proliferation in the C. elegans germ line. We propose a model in which MRG-1 levels are controlled, at least in part, by the proteasome, and that the levels of MRG-1 set a threshold upon which other spatially regulated factors act in order to control the balance between the proliferative fate and differentiation in the C. elegans germ line.
Regulation of hypometabolism: insights into epigenetic controls
Authors: Storey Kenneth B.
Published: January 2015

For many animals, survival of severe environmental stress (e.g. to extremes of heat or cold, drought, oxygen limitation, food deprivation) is aided by entry into a hypometabolic state. Strong depression of metabolic rate, often to only 1–20% of normal resting rate, is a core survival strategy of multiple forms of hypometabolism across the animal kingdom, including hibernation, anaerobiosis, aestivation and freeze tolerance. Global biochemical controls are needed to suppress and reprioritize energy use; one such well-studied control is reversible protein phosphorylation. Recently, we turned our attention to the idea that mechanisms previously associated mainly with epigenetic regulation can also contribute to reversible suppression of gene expression in hypometabolic states. Indeed, situations as diverse as mammalian hibernation and turtle anoxia tolerance show coordinated changes in histone post-translational modifications (acetylation, phosphorylation) and activities of histone deacetylases, consistent with their use as mechanisms for suppressing gene expression during hypometabolism. Other potential mechanisms of gene silencing in hypometabolic states include altered expression of miRNAs that can provide post-transcriptional suppression of mRNA translation and the formation of ribonuclear protein bodies in the nucleus and cytoplasm to allow storage of mRNA transcripts until animals rouse themselves again. Furthermore, mechanisms first identified in epigenetic regulation (e.g. protein acetylation) are now proving to apply to many central metabolic enzymes (e.g. lactate dehydrogenase), suggesting a new layer of regulatory control that can contribute to coordinating the depression of metabolic rate.
Environmentally induced (co)variance in sperm and offspring phenotypes as a source of epigenetic effects
Authors: Marshall Dustin J.
Published: January 2015

Traditionally, it has been assumed that sperm are a vehicle for genes and nothing more. As such, the only source of variance in offspring phenotype via the paternal line has been genetic effects. More recently, however, it has been shown that the phenotype or environment of fathers can affect the phenotype of offspring, challenging traditional theory with implications for evolution, ecology and human in vitro fertilisation. Here, I review sources of non-genetic variation in the sperm phenotype and evidence for co-variation between sperm and offspring phenotypes. I distinguish between two environmental sources of variation in sperm phenotype: the pre-release environment and the post-release environment. Pre-release, sperm phenotypes can vary within species according to male phenotype (e.g. body size) and according to local conditions such as the threat of sperm competition. Post-release, the physicochemical conditions that sperm experience, either when freely spawned or when released into the female reproductive tract, can further filter or modify sperm phenotypes. I find evidence that both pre- and post-release sperm environments can affect offspring phenotype; fertilisation is not a new beginning – rather, the experiences of sperm with the father and upon release can drive variation in the phenotype of the offspring. Interestingly, there was some evidence for co-variation between the stress resistance of sperm and the stress resistance of offspring, though more studies are needed to determine whether such effects are widespread. Overall, it appears that environmentally induced covariation between sperm and offspring phenotypes is non-negligible and further work is needed to determine their prevalence and strength.
Functional characterisation of the chromatically antagonistic photosensitive mechanism of erythrophores in the tilapiaOreochromis niloticus
Authors: Chen Shyh-Chi , Xiao Chengfeng , Troje Nikolaus F. , Robertson R. Meldrum , Hawryshyn Craig W.
Published: January 2015

Non-visual photoreceptors with diverse photopigments allow organisms to adapt to changing light conditions. Whereas visual photoreceptors are involved in image formation, non-visual photoreceptors mainly undertake various non-image-forming tasks. They form specialised photosensory systems that measure the quality and quantity of light and enable appropriate behavioural and physiological responses. Chromatophores are dermal non-visual photoreceptors directly exposed to light and they not only receive ambient photic input but also respond to it. These specialised photosensitive pigment cells enable animals to adjust body coloration to fit environments, and play an important role in mate choice, camouflage and ultraviolet (UV) protection. However, the signalling pathway underlying chromatophore photoresponses and the physiological importance of chromatophore colour change remain under-investigated. Here, we characterised the intrinsic photosensitive system of red chromatophores (erythrophores) in tilapia. Like some non-visual photoreceptors, tilapia erythrophores showed wavelength-dependent photoresponses in two spectral regions: aggregations of inner pigment granules under UV and short-wavelengths and dispersions under middle- and long-wavelengths. The action spectra curve suggested that two primary photopigments exert opposite effects on these light-driven processes: SWS1 (short-wavelength sensitive 1) for aggregations and RH2b (rhodopsin-like) for dispersions. Both western blot and immunohistochemistry showed SWS1 expression in integumentary tissues and erythrophores. The membrane potential of erythrophores depolarised under UV illumination, suggesting that changes in membrane potential are required for photoresponses. These results suggest that SWS1 and RH2b play key roles in mediating intrinsic erythrophore photoresponses in different spectral ranges and this chromatically dependent antagonistic photosensitive mechanism may provide an advantage to detect subtle environmental photic change.
Epigenetics and locust life phase transitions
Authors: Ernst Ulrich R. , Van Hiel Matthias B. , Depuydt Geert , Boerjan Bart , De Loof Arnold , Schoofs Liliane
Published: January 2015

Insects are one of the most successful classes on Earth, reflected in an enormous species richness and diversity. Arguably, this success is partly due to the high degree to which polyphenism, where one genotype gives rise to more than one phenotype, is exploited by many of its species. In social insects, for instance, larval diet influences the development into distinct castes; and locust polyphenism has tricked researchers for years into believing that the drastically different solitarious and gregarious phases might be different species. Solitarious locusts behave much as common grasshoppers. However, they are notorious for forming vast, devastating swarms upon crowding. These gregarious animals are shorter lived, less fecund and transmit their phase characteristics to their offspring. The behavioural gregarisation occurs within hours, yet the full display of gregarious characters takes several generations, as does the reversal to the solitarious phase. Hormones, neuropeptides and neurotransmitters influence some of the phase traits; however, none of the suggested mechanisms can account for all the observed differences, notably imprinting effects on longevity and fecundity. This is why, more recently, epigenetics has caught the interest of the polyphenism field. Accumulating evidence points towards a role for epigenetic regulation in locust phase polyphenism. This is corroborated in the economically important locust species Locusta migratoria and Schistocerca gregaria. Here, we review the key elements involved in phase transition in locusts and possible epigenetic regulation. We discuss the relative role of DNA methylation, histone modification and small RNA molecules, and suggest future research directions.
Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants
Authors: Duclot Florian , Kabbaj Mohamed
Published: January 2015

Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, promoting vulnerability or resilience to the development of depressive-like symptoms. Although the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of MDD remains unclear, its modulation of the efficacy of antidepressants is clearly established. Therefore, in this review, we focus on the epigenetic mechanisms regulating the expression of BDNF in humans and in animal models of depression, and discuss their role in individual differences in vulnerability to depression and response to antidepressant drugs.
Epigenetic linkage of aging, cancer and nutrition
Authors: Daniel Michael , Tollefsbol Trygve O.
Published: January 2015

Epigenetic mechanisms play a pivotal role in the expression of genes and can be influenced by both the quality and quantity of diet. Dietary compounds such as sulforaphane (SFN) found in cruciferous vegetables and epigallocatechin-3-gallate (EGCG) in green tea exhibit the ability to affect various epigenetic mechanisms such as DNA methyltransferase (DNMT) inhibition, histone modifications via histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition, or noncoding RNA expression. Regulation of these epigenetic mechanisms has been shown to have notable influences on the formation and progression of various neoplasms. We have shown that an epigenetic diet can influence both cellular longevity and carcinogenesis through the modulation of certain key genes that encode telomerase and p16. Caloric restriction (CR) can also play a crucial role in aging and cancer. Reductions in caloric intake have been shown to increase both the life- and health-span in a variety of animal models. Moreover, restriction of glucose has been demonstrated to decrease the incidence of age-related diseases such as cancer and diabetes. A diet rich in compounds such as genistein, SFN and EGCG can positively modulate the epigenome and lead to many health benefits. Also, reducing the quantity of calories and glucose in the diet can confer an increased health-span, including reduced cancer incidence.
Twin methodology in epigenetic studies
Authors: Tan Qihua , Christiansen Lene , von Bornemann Hjelmborg Jacob , Christensen Kaare
Published: January 2015

Since the final decades of the last century, twin studies have made a remarkable contribution to the genetics of human complex traits and diseases. With the recent rapid development in modern biotechnology of high-throughput genetic and genomic analyses, twin modelling is expanding from analysis of diseases to molecular phenotypes in functional genomics especially in epigenetics, a thriving field of research that concerns the environmental regulation of gene expression through DNA methylation, histone modification, microRNA and long non-coding RNA expression, etc. The application of the twin method to molecular phenotypes offers new opportunities to study the genetic (nature) and environmental (nurture) contributions to epigenetic regulation of gene activity during developmental, ageing and disease processes. Besides the classical twin model, the case co-twin design using identical twins discordant for a trait or disease is becoming a popular and powerful design for epigenome-wide association study in linking environmental exposure to differential epigenetic regulation and to disease status while controlling for individual genetic make-up. It can be expected that novel uses of twin methods in epigenetic studies are going to help with efficiently unravelling the genetic and environmental basis of epigenomics in human complex diseases.
Dynamics of epigenetic phenomena: intergenerational and intragenerational phenotype ‘washout’
Authors: Burggren Warren W.
Published: January 2015

Epigenetic studies of both intragenerational and transgenerational epigenetic phenotypic modifications have proliferated in the last few decades. However, the strong reductionist focus on mechanism that prevails in many epigenetic studies to date has diverted attention away what might be called the ‘dynamics’ of epigenetics and its role in comparative biology. Epigenetic dynamics describes how both transgenerational and intragenerational epigenetic phenotypic modifications change in non-linear patterns over time. Importantly, a dynamic perspective suggests that epigenetic phenomena should not be regarded as ‘digital’ (on–off), in which a modified trait necessarily suddenly disappears between one generation and the next. Rather, dynamic epigenetic phenomena may be better depicted by graded, time-related changes that can potentially involve the ‘washout’ of modified phenotype both within and across generations. Conceivably, an epigenetic effect might also ‘wash-in’ over multiple generations, and there may be unexplored additive effects resulting from the pressures of environmental stressors that wax, wane and then wax again across multiple generations. Recognition of epigenetic dynamics is also highly dependent on the threshold for detection of the phenotypic modification of interest, especially when phenotypes wash out or wash in. Thus, studies of transgenerational epigenetic effects (and intragenerational effects, for that matter) that search for persistence of the phenomenon are best conducted with highly sensitive, precise quantitative methods. All of the scenarios in this review representing epigenetic dynamics are possible and some even likely. Focused investigations that concentrate on the time course will reveal much about both the impact and mechanisms of epigenetic phenomena.
New insights into mechanisms that regulate DNA methylation patterning
Authors: Ficz Gabriella
Published: January 2015

From a fertilised egg to a mature organism, cells divide and accumulate epigenetic information, which is faithfully passed on to daughter cells. DNA methylation consolidates the memory of the developmental history and, albeit very stable, it is not immutable and DNA methylation patterns can be deconstructed – a process that is essential to regain totipotency. Research into DNA methylation erasure gained momentum a few years ago with the discovery of 5-hydroxymethylcytosine, an oxidation product of 5-methylcytosine. The role of this new epigenetic modification in DNA demethylation and other potential epigenetic roles are discussed here. But what are the mechanisms that regulate deposition of epigenetic modifications? Until recently, limited direct evidence indicated that signalling molecules are able to modulate the function of epigenetic modifiers, which shape the epigenome in the nucleus of the cell. New reports in embryonic stem cell model systems disclosed a tight relationship between major signalling pathways and the DNA methylation machinery, which opens up exciting avenues in the relationship between external signals and epigenetic memory. Here, I discuss mechanisms and concepts in DNA methylation patterning, the implications in normal development and disease, and future directions.
Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism
Authors: Tarrade Anne , Panchenko Polina , Junien Claudine , Gabory Anne
Published: January 2015

The recent and rapid worldwide increase in non-communicable diseases challenges the assumption that genetic factors are the primary contributors to such diseases. A new concept of the ‘developmental origins of health and disease’ (DOHaD) is at stake and therefore requires a paradigm shift. Maternal obesity and malnutrition predispose offspring to develop metabolic syndrome, a vicious cycle leading to transmission to subsequent generation(s), with differences in response and susceptibility according to the sex of the individual. The placenta is a programming agent of adult health and disease. Adaptations of placental phenotype in response to maternal diet and metabolic status alter fetal nutrient supply. This implies important epigenetic changes that are, however, still poorly documented in DOHaD studies, particularly concerning overnutrition. The aim of this review is to discuss the emerging knowledge on the relationships between the effect of maternal nutrition or metabolic status on placental function and the risk of diseases later in life, with a specific focus on epigenetic mechanisms and sexual dimorphism. Explaining the sex-specific causal variables and how males versus females respond and adapt to environmental perturbations should help physicians and patients to anticipate disease susceptibility.
The expanding epigenetic landscape of non-model organisms
Authors: Bonasio Roberto
Published: January 2015

Epigenetics studies the emergence of different phenotypes from a single genotype. Although these processes are essential to cellular differentiation and transcriptional memory, they are also widely used in all branches of the tree of life by organisms that require plastic but stable adaptation to their physical and social environment. Because of the inherent flexibility of epigenetic regulation, a variety of biological phenomena can be traced back to evolutionary adaptations of few conserved molecular pathways that converge on chromatin. For these reasons chromatin biology and epigenetic research have a rich history of chasing discoveries in a variety of model organisms, including yeast, flies, plants and humans. Many more fascinating examples of epigenetic plasticity lie outside the realm of model organisms and have so far been only sporadically investigated at a molecular level; however, recent progress on sequencing technology and genome editing tools have begun to blur the lines between model and non-model organisms, opening numerous new avenues for investigation. Here, I review examples of epigenetic phenomena in non-model organisms that have emerged as potential experimental systems, including social insects, fish and flatworms, and are becoming accessible to molecular approaches.
Shiver me titin! Elucidating titin's role in shivering thermogenesis
Authors: Taylor-Burt Kari R. , Monroy Jenna , Pace Cinnamon , Lindstedt Stan , Nishikawa Kiisa C.
Published: January 2015

Shivering frequency scales predictably with body mass and is 10 times higher in a mouse than a moose. The link between shivering frequency and body mass may lie in the tuning of muscle elastic properties. Titin functions as a muscle ‘spring’, so shivering frequency may be linked to titin's structure. The muscular dystrophy with myositis (mdm) mouse is characterized by a deletion in titin's N2A region. Mice that are homozygous for the mdm mutation have a lower body mass, stiffer gait and reduced lifespan compared with their wild-type and heterozygous siblings. We characterized thermoregulation in these mice by measuring metabolic rate and tremor frequency during shivering. Mutants were heterothermic at ambient temperatures of 20–37°C while wild-type and heterozygous mice were homeothermic. Metabolic rate increased at smaller temperature differentials (i.e. the difference between body and ambient temperatures) in mutants than in non-mutants. The difference between observed tremor frequencies and shivering frequencies predicted by body mass was significantly larger for mutant mice than for wild-type or heterozygous mice, even after accounting for differences in body temperature. Together, the heterothermy in mutants, the increase in metabolic rate at low temperature differentials and the decreased tremor frequency demonstrate the thermoregulatory challenges faced by mice with the mdm mutation. Oscillatory frequency is proportional to the square root of stiffness, and we observed that mutants had lower active muscle stiffness in vitro. The lower tremor frequencies in mutants are consistent with reduced active muscle stiffness and suggest that titin affects the tuning of shivering frequency.
Selection for upper thermal tolerance in rainbow trout (Oncorhynchus mykissWalbaum)
Authors: Chen Zhongqi , Snow Michael , Lawrence Craig S. , Church Anthony R. , Narum Shawn R. , Devlin Robert H. , Farrell Anthony P.
Published: January 2015

Rainbow trout (Oncorhynchus mykiss Walbaum) in southern Western Australia have undergone passive selection for over 19 generations to survive high water temperatures. Based on the conceptual model of ‘oxygen- and capacity-limited thermal tolerance’, we measured critical thermal maximum (CTmax), maximum heart rate (fH,max) and aerobic scope to test the hypothesis that these rainbow trout can maintain aerobic scope at high temperatures through a robust cardiac performance supporting oxygen delivery. Across five family groups CTmax averaged 29.0±0.02°C. Aerobic scope was maximized at 15.8±0.3°C (Topt), while the upper pejus temperature (Tpej, set at 90% of maximum aerobic scope) was 19.9±0.3°C. Although aerobic scope decreased at temperatures above Topt, the value at 25°C remained well over 40% of the maximum. Furthermore, pharmacologically stimulated fH,max increased with temperature, reaching a peak value between 23.5±0.4 and 24.0±0.4°C (Tmax) for three family groups. The Arrhenius breakpoint temperature (TAB) for fH,max was 20.3±0.3 to 20.7±0.4°C, while the average Q10 breakpoint temperature (TQB, when the incremental Q10<1.6) for fH,max was 21.6±0.2 to 22.0±0.4°C. Collectively, fH,max progressively became less temperature dependent beyond 20°C (TAB and TQB), which coincides with the upper Tpej for aerobic scope. Although upper thermal performance indices for both aerobic scope and fH,max were compared among family groups in this population, appreciable differences were not evident. Compared with other populations of rainbow trout, the present assessment is consistent with the prediction that this strain has undergone selection and shows the ability to tolerate higher water temperatures.