Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.

Neurons Activated During Fear Memory Consolidation and Reconsolidation are Mapped to a Common and New Topography in the Lateral Amygdala

A key question in neuroscience is how memory is selectively allocated to neural networks in the brain. This question remains a significant research challenge, in both rodent models and humans alike, because of the inherent difficulty in tracking and deciphering large, highly dimensional neuronal ensembles that support memory (i.e., the engram). In a previous study we showed that consolidation of a new fear memory is allocated to a common topography of amygdala neurons. When a consolidated memory is retrieved, it may enter a labile state, requiring reconsolidation for it to persist. What is not known is whether the original spatial allocation of a consolidated memory changes during reconsolidation. Knowledge about the spatial allocation of a memory, during consolidation and reconsolidation, provides fundamental insight into its core physical structure (i.e., the engram). Using design-based stereology, we operationally define reconsolidation by showing a nearly identical quantity of neurons in the dorsolateral amygdala (LAd) that expressed a plasticity-related protein, phosphorylated mitogen-activated protein kinase, following both memory acquisition and retrieval. Next, we confirm that Pavlovian fear conditioning recruits a stable, topographically organized population of activated neurons in the LAd. When the stored fear memory was briefly reactivated in the presence of the relevant conditioned stimulus, a similar topography of activated neurons was uncovered. In addition, we found evidence for activated neurons allocated to new regions of the LAd. These findings provide the first insight into the spatial allocation of a fear engram in the LAd, during its consolidation and reconsolidation phase.

Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Validating a novel, low cost, automated malnutrition screening system as a predictor of nutritional risk in the Oncology Day Care Unit

Background Cancer-related malnutrition is associated with increased morbidity, poorer tolerance of treatment, decreased quality of life, increased hospital admissions, and increased health care costs (Isenring et al., 2013). This study’s aim was to determine whether a novel, automated screening system was a useful tool for nutrition screening when compared against a full nutrition assessment using the Patient-Generated Subjective Global Assessment (PG-SGA) tool. Methods A single site, observational, cross-sectional study was conducted in an outpatient oncology day care unit within a Queensland tertiary facility, with three hundred outpatients (51.7% male, mean age 58.6 ± 13.3 years). Eligibility criteria: ≥18 years, receiving anticancer treatment, able to provide written consent. Patients completed the Malnutrition Screening Tool (MST). Nutritional status was assessed using the PG-SGA. Data for the automated screening system was extracted from the pharmacy software program Charm. This included body mass index (BMI) and weight records dating back up to six months. Results The prevalence of malnutrition was 17%. Any weight loss over three to six weeks prior to the most recent weight record as identified by the automated screening system relative to malnutrition resulted in 56.52% sensitivity, 35.43% specificity, 13.68% positive predictive value, 81.82% negative predictive value. MST score 2 or greater was a stronger predictor of nutritional risk relative to PG-SGA classified malnutrition (70.59% sensitivity, 69.48% specificity, 32.14% positive predictive value, 92.02% negative predictive value). Conclusions Both the automated screening system and the MST fell short of the accepted professional standard for sensitivity (80%) or specificity (60%) when compared to the PG-SGA. However, although the MST remains a better predictor of malnutrition in this setting, uptake of this tool in the Oncology Day Care Unit remains challenging.

Methodological developments in phenomenography : investing using information to learn in the discipline classroom

This paper discusses methodological developments in phenomenography that make it apropos for the study of teaching and learning to use information in educational environments. Phenomenography is typically used to analyze interview data to determine different ways of experiencing a phenomenon. There is an established tradition of phenomenographic research in the study of information literacy (ex: Bruce, 1997; 2008; Lupton, 2008; Webber, Boon, & Johnston, 2005). Drawing from the large body of evidence complied in two decades of research, phenomenographers developed variation theory, which explains what a learner can feasibly learn from a classroom lesson based on how the phenomenon being studied is presented (Marton, Runesson, & Tsui, 2004). Variation theory’s ability to establish the critical conditions necessary for learning to occur has resulted in the use of phenomenographic methods to study classroom interactions by collecting and analyzing naturalistic data through observation, as well as interviews concerning teachers’ intentions and students’ different experiences of classroom lessons. Describing the methodological developments of phenomenography in relation to understanding the classroom experience, this paper discusses the potential benefits and challenges of utilizing such methods to research the experiences of teaching and learning to use information in discipline-focused classrooms. The application of phenomenographic methodology for this purpose is exemplified with an ongoing study that explores how students learned to use information in an undergraduate language and gender course (Maybee, Bruce, Lupton, & Rebmann, in press). This paper suggests that by providing a nuanced understanding of what is intended for students to learn about using information, and relating that to what transpires in the classroom and how students experience these lessons, phenomenography and variation theory offer a viable framework for further understanding and improving how students are taught, and learn to use information.

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Prostacyclin synthase and thromboxane synthase signaling via arachidonic acid metabolism affects a number of tumor cell survival pathways such as cell proliferation, apoptosis, tumor cell invasion and metastasis, and angiogenesis. However, the effects of these respective synthases differ considerably with respect to the pathways described. While prostacyclin synthase is generally believed to be anti-tumor, a pro-carcinogenic role for thromboxane synthase has been demonstrated in a variety of cancers. The balance of oppositely-acting COX-derived prostanoids influences many processes throughout the body, such as blood pressure regulation, clotting, and inflammation. The PGI2/TXA2 ratio is of particular interest in-vivo, with the corresponding synthases shown to be differentially regulated in a variety of disease states. Pharmacological inhibition of thromboxane synthase has been shown to significantly inhibit tumor cell growth, invasion, metastasis and angiogenesis in a range of experimental models. In direct contrast, prostacyclin synthase overexpression has been shown to be chemopreventive in a murine model of the disease, suggesting that the expression and activity of this enzyme may protect against tumor development. In this review, we discuss the aberrant expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. We discuss the effects of these enzymes on a range of tumor cell survival pathways, such as tumor cell proliferation, induction of apoptosis, invasion and metastasis, and tumor cell angiogenesis. As downstream signaling pathways of these enzymes have also been implicated in cancer states, we examine the role of downstream effectors of PGIS and TXS activity in tumor growth and progression. Finally, we discuss current therapeutic strategies aimed at targeting these enzymes for the prevention/treatment of cancer. © 2010 Elsevier B.V. All rights reserved.

Segmental torso masses and joint torques produced by gravity in the adolescent scoliotic spine

Introduction Calculating segmental torso masses in Adolescent Idiopathic Scoliosis (AIS) patients allows the gravitational loading on the scoliotic spine during relaxed standing to be estimated. Methods Low dose CT data was used to calculate vertebral level-by-level torso masses and spinal joint torques for 20 female AIS patients (mean age 15.0 ± 2.7 years, mean Cobb angle 53 ± 7.1°). ImageJ software (v1.45 NIH USA) was used to threshold the T1 to L5 CT images and calculate the segmental torso volume and mass for each vertebral level. Masses for the head, neck and arms were taken from published data.1 Intervertebral joint torques in the coronal and sagittal planes at each vertebral level were found from the position of the centroid of the segment masses relative to the joint centres (assumed to be at the centre of the intervertebral disc). The joint torque at each level was found by summing torque contributions for all segments above that joint. Results Segmental torso mass increased from 0.6kg at T1 to 1.5kg at L5. The coronal plane joint torques due to gravity were 5-7Nm at the apex of the curve; sagittal torques were 3-5.4Nm. Conclusion CT scans were in the supine position and curve magnitudes are known to be smaller than those in standing.2 Hence, this study has shown that gravity produces joint torques potentially of higher than 7Nm in the coronal plane and 5Nm in the sagittal plane during relaxed standing in scoliosis patients. The magnitude of these torques may help to explain the mechanics of AIS progression and the mechanics of bracing. This new data on torso segmental mass in AIS patients will assist biomechanical models of scoliosis.

Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer : potential targets for chemoprevention and systemic therapy

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Defense and counterdefense in the plant world

An important role of RNA interference (RNAi)-like pathways in plants is defense against viral infection. Viruses can overcome this defense by expressing proteins that suppress the pathway. A new study of Agrobacterium tumefaciens infection reveals that this plant pathogen, although a bacterium, also induces and then suppresses the host RNAi response. © 2006 Nature Publishing Group.

Changes in the site distribution of common melanoma subtypes in Queensland, Australia over time: implications for public health campaigns

Abstract BACKGROUND: An examination of melanoma incidence according to anatomical region may be one method of monitoring the impact of public health initiatives. OBJECTIVES:   To examine melanoma incidence trends by body site, sex and age at diagnosis or body site and morphology in a population at high risk. MATERIALS AND METHODS:   Population-based data on invasive melanoma cases (n = 51473) diagnosed between 1982 and 2008 were extracted from the Queensland Cancer Registry. Age-standardized incidence rates were calculated using the direct method (2000 world standard population) and joinpoint regression models were used to fit trend lines. RESULTS:   Significantly decreasing trends for melanomas on the trunk and upper limbs/shoulders were observed during recent years for both sexes under the age of 40 years and among males aged 40-59years. However, in the 60 and over age group, the incidence of melanoma is continuing to increase at all sites (apart from the trunk) for males and on the scalp/neck and upper limbs/shoulders for females. Rates of nodular melanoma are currently decreasing on the trunk and lower limbs. In contrast, superficial spreading melanoma is significantly increasing on the scalp/neck and lower limbs, along with substantial increases in lentigo maligna melanoma since the late 1990s at all sites apart from the lower limbs. CONCLUSIONS:   In this large study we have observed significant decreases in rates of invasive melanoma in the younger age groups on less frequently exposed body sites. These results may provide some indirect evidence of the impact of long-running primary prevention campaigns.

Soybean dwarf luteovirus contains the third variant genome type in the luteovirus group

Complementary DNAs covering the entire RNA genome of soybean dwarf luteovirus (SDV) were cloned and sequenced. Computer analysis of the 5861 nucleotide sequence revealed five major open reading frames (ORFs) possessing conservation of sequence and organisation with known luteovirus sequences. Comparative analyses of the genome structure show that SDV shares sequence homology and features of gene organisation with barley yellow dwarf virus (PAV isolate) in the 5' half of the genome, yet is more closely related to potato leafroll virus in its 3' coding regions. In addition, SDV differs from other known luteoviruses in possessing an exceptionally long 3' terminal sequence with no apparent coding capacity. We conclude from these data that the SDV genome represents a third variant genome type in the luteovirus group.

Sex hormone regulation of innate immunity in the female reproductive tract : the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens

The immune system in the female reproductive tract (FRT) does not mount an attack against HIV or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the female reproductive tract. Working together, these antimicrobials along with mucosal antibodies attack many different viral, bacterial and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus have evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells and other immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate immune response is under hormonal control, varies with the stage of the menstrual cycle, and as such is suppressed at mid-cycle to optimize conditions for successful fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets.

Collagen in the scarless fetal skin wound : detection with picrosirius-polarization

Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a "response" to burn injury.

A randomised controlled trial of amniotic membrane in the treatment of a standardised burn injury in the merino lamb

Burn injury is associated with disabling scar formation which impacts on many aspects of the patient's life. Previously we have shown that the fetus heals a deep dermal burn in a scarless fashion. Amniotic membrane (AM) is the outermost fetal tisue and has beeen used as a dressing in thermal injuries, though there is little data to support this use. To assess the efficacy of AM in scar minimisation after deep dermal burn wound, we conducted a randomised controlled study in the 1-month lamb. Lambs were delivered by caesarian section and the amniotic membranes stored after which lambs were returned to their mothers post-operatively. At 1 month, a standardised deep dermal burn was created under general anaesthesia on both flanks of the lamb. One flank was covered with unmatched AM, the other with paraffin gauze. Animals were sequentially euthanased from Day 3-60 after injury and tissue analysed for histopathology and immunohistochemically for alpha-smooth muscle actin (alphaSMA) content. AM resulted in reduced scar tissue as assessed histopathologically and reduced alphaSMA content. This study provides the first laboratory evidence that AM may reduce scar formation after burn injury.

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.