Femoral neck geometry and hip fracture risk : the Geelong Osteoporosis Study

To determine the relationship between femoral neck geometry and the risk of hip fracture in post-menopausal Caucasian women, we conducted a retrospective study comparing the femoral neck dimensions of 62 hip fracture cases to those of 608 randomly selected controls. Measurements were made from dual-energy X-ray absorptiometry scans (Lunar DPX-L), using the manufacturers ruler function, and included: hip axis length (HAL), femoral neck axis length (FNAL), femoral neck width (FNW), femoral shaft width (FSW), medial femoral shaft cortical thickness (FSCT_med), and lateral femoral shaft cortical thickness (FSCT_lat). The fracture group was older (median age 78.3 years vs 73.8 years), lighter (median weight 59.9 kg vs 64.5 kg), and, after adjustment for age, taller (mean height 158.7±0.8 cm vs 156.7±0.2 cm) than the controls. Furthermore, bone mineral density was lower in this group (0.682±0.016 g/cm² vs 0.791±0.006 g/cm²). After adjustment for age, bone mineral content (BMC) or height, hip fracture patients had greater FNW (up to 6.6%) and FSW (up to 6.3%) than did the controls. Each standard deviation increase in FNW and FSW was associated with a 1.7-fold (95% CI 1.3–2.3) and a 2.4-fold (95% CI 1.8–3.2) increase in the fracture risk, respectively. BMC-adjusted FNAL was greater in the fracture group (+2.1%) than in the controls, while the age-adjusted FSCT_med was reduced (–7.2%). There was a trend towards longer HAL (up to 2.1%) after adjustment for age or BMC, and thinner age-adjusted FSCT_lat (–1.7%) in fracture patients that did not reach statistical significance. In multivariate analysis, the risk of hip fracture was predicted by the combination of age, FNW, FSW, BMC and FSCT_med. HAL was not analyzed because of the small number of HAL measurements among fracture cases. We conclude that post-menopausal women with hip fractures have wider femoral necks and shafts, thinner femoral cortices and longer femoral neck axis lengths than do women with no fractures. Alteration in hip geometry is associated with the risk of hip fracture.

In vitro behavior of human osteoblast-like cells (SaOS2) cultured on surface modified titanium and titanium–zirconium alloy

In this study, titanium (Ti) and titanium-zirconium (TiZr) alloy samples fabricated through powder metallurgy were surface modified by alkali-heat treatment and calcium (Ca)-ion-deposition. The alteration of the surface morphology and the chemistry of the Ti and TiZr after surface modification were examined. The bioactivity of the Ti and TiZr alloys after the surface modification was demonstrated. Subsequently, the cytocompatibility of the surface modified Ti and TiZr was evaluated via in vitro cell culture using human osteoblast-like cells (SaOS2). The cellular attachment, adhesion and proliferation after cell culture for 14 days were characterized by scanning electron microscopy (SEM) and MTT assay. The relationship between surface morphology and chemical composition of the surface modified Ti and TiZr and cellular responses was investigated. Results indicated that the surface-modified Ti and TiZr alloys exhibited excellent in vitro cytocompatibility together with satisfactory bioactivity. Since osteoblast adhesion and proliferation are essential prerequisites for a successful implant in vivo, these results provide evidence that Ti and TiZr alloys after appropriate surface modification are promising biomaterials for hard tissue replacement.

The antimicrobial efficacy of elaeis guineensis : characterization, in Vitro and in Vivo studies

The urgent need to treat multi-drug resistant pathogenic microorganisms in chronically infected patients has given rise to the development of new antimicrobials from natural resources. We have tested Elaeis guineensis Jacq (Arecaceae) methanol extract against a variety of bacterial, fungal and yeast strains associated with infections. Our studies have demonstrated that E. guineensis exhibits excellent antimicrobial activity in vitro and in vivo against the bacterial and fungal strains tested. A marked inhibitory effect of the E. guineensis extracts was observed against C. albicans whereby E. guineensis extract at =, 1, or 2 times the MIC significantly inhibited C. albicans growth with a noticeable drop in optical density (OD) of the bacterial culture. This finding confirmed the anticandidal activity of the extract on C. albicans. Imaging using scanning (SEM) and transmission (TEM) electron microscopy was done to determine the major alterations in the microstructure of the extract-treated C. albicans. The main abnormalities noted via SEM and TEM studies were the alteration in morphology of the yeast cells. In vivo antimicrobial activity was studied in mice that had been inoculated with C. albicans and exhibited good anticandidal activity. The authors conclude that the extract may be used as a candidate for the development of anticandidal agent.

Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet

The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration.

HIV-1 down-modulates γ signaling chain of FcγR in human macrophages : a possible mechanism for inhibition of phagocytosis

HIV-1 infection impairs a number of macrophage effector functions, thereby contributing to development of opportunistic infections and the pathogenesis of AIDS. FcγR-mediated phagocytosis by human monocyte-derived macrophages (MDM) is inhibited by HIV-1 infection in vitro, and the underlying mechanism was investigated in this study. Inhibition of phagocytosis directly correlated with the multiplicity of HIV-1 infection. Expression of surface FcγRs was unaffected by HIV-1 infection, suggesting that inhibition of phagocytosis occurred during or after receptor binding. HIV-1 infection of MDM markedly inhibited tyrosine phosphorylation of the cellular proteins, which occurs following engagement of FcγRs, suggesting a defect downstream of initial receptor activation. FcγR-mediated phagocytosis in HIV-infected MDM was associated with inhibition of phosphorylation of tyrosine kinases from two different families, Hck and Syk, defective formation of Syk complexes with other tyrosine-phosphorylated proteins, and inhibition of paxillin activation. Down-modulation of protein expression but not mRNA of the γ signaling subunit of FcγR (a docking site for Syk) was observed in HIV-infected MDM. Infection of MDM with a construct of HIV-1 in which nef was replaced with the gene for the γ signaling subunit augmented FcγR-mediated phagocytosis, suggesting that down-modulation of γ-chain protein expression in HIV-infected MDM caused the defective FcγR-mediated signaling and impairment of phagocytosis. This study is the first to demonstrate a specific alteration in phagocytosis signal transduction pathway, which provides a mechanism for the observed impaired FcγR-mediated phagocytosis in HIV-infected macrophages and contributes to the understanding of how HIV-1 impairs cell-mediated immunity leading to HIV-1 disease progression.

Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1

Human immunodeficiency virus (HIV) particles produced in COS-7 cells transfected with HIV type 1 (HIV-1) proviral DNA contain 8 molecules of tRNA(3Lys) per 2 molecules of genomic RNA and 12 molecules of tRNA1,2Lys per 2 molecules of genomic RNA. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a human tRNA3Lys gene, there is a large increase in the amount of cytoplasmic tRNA3Lys per microgram of total cellular RNA, and the tRNA3Lys content in the virus increases from 8 to 17 molecules per 2 molecules of genomic RNA. However, the total number of tRNALys molecules per 2 molecules of genomic RNA remains constant at 20; i.e., the viral tRNA1,2Lys content decreases from 12 to 3 molecules per 2 molecules of genomic RNA. All detectable tRNA3Lys is aminoacylated in the cytoplasm of infected cells and deacylated in the virus. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a mutant amber suppressor tRNA3Lys gene (in which the anticodon is changed from TTT to CTA), there is also a large increase in the relative concentration of cytoplasmic tRNA3Lys, and the tRNA3Lys content in the virus increases from 8 to 15 molecules per 2 molecules of genomic RNA, with a decrease in viral tRNA1,2Lys from 12 to 5 molecules per 2 molecules of genomic RNA. Thus, the total number of molecules of tRNALys in the virion remains at 20. The alteration of the anticodon has little effect on the viral packaging of this mutant tRNA in spite of the fact that it no longer contains the modified base mcm 5s2U at position 34, and its ability to be aminoacylated is significantly impaired compared with that of wild-type tRNA3Lys. Viral particles which have incorporated either excess wild-type tRNA3Lys or mutant suppressor tRNA3Lys show no differences in viral infectivity compared with wild-type HIV-1.

Zinc and docosahexaenoic acid metabolism in brain cells

This thesis examines the direct interaction of Docosahexaenoic acid (DHA, an omega-3 fatty acid) against zinc-induced mitochondrial dysfunction and involvement of bioenergetic regulation as a zinc toxicity target, which may be the initiator of oxidative stress, caspase cascade, alteration in epigenetic patterns and therefore gene expression in human neuronal cells.

State-related alterations of gene expression in bipolar disorder : a systematic review

Objective:  Alterations in gene expression in bipolar disorder have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related.

Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications.

Results:  A total of 17 studies were included, comprising 565 patients and 418 control individuals. Six studies evaluated intraindividual alterations in gene expression across mood states. Two of five studies found evidence of intraindividual alterations in gene expression between a depressed state and a euthymic state. No studies evaluated intraindividual differences in gene expression between a manic state and a euthymic state, while only one case study evaluated differences between a manic state and a depressed state, finding altered expression in seven genes. No study investigated intraindividual variations in gene expression between a euthymic state and multiple states of various polarities (depressive, manic, hypomanic). Intraindividual alterations in expression of the same genes were not investigated across studies. Only one gene (the brain-derived neurotrophic factor gene; BDNF) was investigated across multiple studies, showing no alteration between bipolar disorder patients and control individuals.

Conclusions:  There is evidence of some genes exhibiting state-related alterations in expression in bipolar disorder; however, this finding is limited by the lack of replication across studies. Further prospective studies are warranted, measuring gene expression in various affective phases, allowing for assessment of intraindividual differences.

Addressing aquaculture-fisheries interactions through the implementation of the ecosystem approach to aquaculture (EAA

This review addresses how the ecosystem approach to aquaculture (EAA) can optimize aquaculture-fisheries interactions considering different spatial scales from farm, aquaculture zone and watershed through to the global market. Aquaculture and fisheries are closely related subsectors with frequent interactions, largely due to the sharing of common ecosystems and natural resources. Interactions are also born from the flow of biomass from fisheries to aquaculture through fish-based feeds (e.g. fishmeal, fish oil and trashfish), through the collection of wild seed and brookstock, and genetic resources and biomass transfer from aquaculture to fisheries through culture-based fisheries (CBF) and escapees. Negative effects include modification of habitats affecting fisheries resources and activities (e.g. mangrove clearing for shrimp ponds, seabed disturbances through anchoring of aquaculture cages or pens, damage to seagrasses, alteration to reproductive habitats, biodiversity loss). Eutrophication of waterbodies due to excess nutrient release leading to anoxia and fish mortality can also impact negatively on biodiversity and wild fish stocks. Release of diseases and chemicals also imposes some threats on fisheries. Yet there could be beneficial impacts; for example, aquaculture is increasingly contributing to capture fisheries through CBF and could contribute to restore overfished stocks. Aquaculture can offer alternative livelihoods to fisherfolk, providing increased opportunity to them and also to their families, and especially to women. Aquaculture-increased production and marketing can also enhance and indirectly improve processing and market access to similar fishery products. The ecosystem approach to aquaculture (EAA) is a strategy for the management of the sector that emphasizes intersectoral complementarities by taking into account the interactions between all the activities within ecologically meaningful boundaries and acknowledging the multiple services provided by ecosystems. The main objective of this review is to understand the status of aquaculture-fisheries interactions associated with the biological, technological, social, economic, environmental, policy, legal and other aspects of aquaculture development and to analyze how these interactions are or could be addressed with an EAA. Therefore, the review involves aspects of scoping, identification of issues, prioritizing, devising management tools and plans for minimizing negative effects and optimizing positive ones within the context of social-ecological resilience, at different relevant geographical scales. Many of the management measures suggested in this review must involve not only EAA but also an ecosystem approach to fisheries (EAF), especially to deal with issues such as fishery of wild seed and the management of fisheries to produce fishmeal/oil for pelleted feeds or for direct feeding with wet fish. The implementation of EAA and EAF should help to overcome the sectoral and intergovernmental fragmentation of resource management efforts and assist in the development of institutional mechanisms and private-sector arrangements for effective coordination among various sectors active in ecosystems in which aquaculture and fisheries operate and between the various levels of government. Ecosystem-based management involves a transition from traditional sectoral planning and decision-making to the application of a more holistic approach to integrated natural resource management in an adaptive manner.

Human neuronal cells : epigenetic aspects

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) promote histone posttranslational modifications, which lead to an epigenetic alteration in gene expression. Aberrant regulation of HATs and HDACs in neuronal cells results in pathological consequences such as neurodegeneration. Alzheimer's disease is the most common neurodegenerative disease of the brain, which has devastating effects on patients and loved ones. The use of pan-HDAC inhibitors has shown great therapeutic promise in ameliorating neurodegenerative ailments. Recent evidence has emerged suggesting that certain deacetylases mediate neurotoxicity, whereas others provide neuroprotection. Therefore, the inhibition of certain isoforms to alleviate neurodegenerative manifestations has now become the focus of studies. In this review, we aimed to discuss and summarize some of the most recent and promising findings of HAT and HDAC functions in neurodegenerative diseases.

Skeletal muscle fat metabolism after exercise in humans: influence of fat availability

The mechanisms facilitating increased skeletal muscle fat oxidation following prolonged, strenuous exercise remain poorly defined. The aim of this study was to examine the influence of plasma free fatty acid (FFA) availability on intramuscular malonyl-CoA concentration and the regulation of whole-body fat metabolism during a 6-h postexercise recovery period. Eight endurance-trained men performed three trials, consisting of 1.5 h high-intensity and exhaustive exercise, followed by infusion of saline, saline + nicotinic acid (NA; low FFA), or Intralipid and heparin [high FFA (HFA)]. Muscle biopsies were obtained at the end of exercise (0 h) and at 3 and 6 h in recovery. Ingestion of NA suppressed the postexercise plasma FFA concentration throughout recovery (P < 0.01), except at 4 h. The alteration of the availability of plasma FFA during recovery induced a significant increase in whole-body fat oxidation during the 6-h period for HFA (52.2 ± 4.8 g) relative to NA (38.4 ± 3.1 g; P < 0.05); however, this response was unrelated to changes in skeletal muscle malonyl-CoA and acetyl-CoA carboxylase (ACC)β phosphorylation, suggesting mechanisms other than phosphorylation-mediated changes in ACC activity may have a role in regulating fat metabolism in human skeletal muscle during postexercise recovery. Despite marked changes in plasma FFA availability, no significant changes in intramuscular triglyceride concentrations were detected. These data suggest that the regulation of postexercise skeletal muscle fat oxidation in humans involves factors other than the 5′AMP-activated protein kinase-ACCβ-malonyl-CoA signaling pathway, although malonyl-CoA-mediated regulation cannot be excluded completely in the acute recovery period.

Isolation breeds naivety : island living robs Australian varanid lizards of toad-toxin immunity via four-base-pair mutation

Since their introduction to the toad-free Australian continent cane toads (Bufo marinus) have caused a dramatic increase in naïve varanid mortality when these large lizards attempt to feed on this toxic amphibian. In contrast Asian–African varanids, which have coevolved with toads, are resistant to toad toxin. Toad toxins, such as Bufalin target the H1-H2 domain of the α1 subunit of the sodium-potassium-ATPase enzyme. Sequencing of this domain revealed identical nucleotide sequences in four Asian as well as in three African varanids, and identical sequences in all 11 Australian varanids. However, compared to the Asian–African varanids, the Australian varanids showed four-base-pair substitutions, resulting in the alteration in three of the 12 amino acids representing the H1-H2 domain. The phenotypic effect of the substitutions was investigated in human embryonic kidney (HEK) 293 cells stably transfected with the Australian and the Asian–African H1-H2 domains. The transfections resulted in an approximate 3000-fold reduction in resistance to Bufalin in the Australian HEK293 cells compared to the Asian–African HEK293 cells, demonstrating the critical role of this minor mutation in providing Bufalin resistance. Our study hence presents a clear link between genotype and phenotype, a critical step in understanding the evolution of phenotypic diversity.

Thai cyber-actors : evidence of an Islamophobic effect

The long-standing Patani Muslim separatist resistance of Southern Thailand is not one that is well known, and its contemporaneous spill over onto the Internet even less so. The more radical Patani online propaganda is in fact symptomatic of the relocation of the struggle within the sphere of influence of global jihadism, distancing itself from the ethno-nationalism characteristic of a previous generation of fighters. New media propaganda, in particular Jihad 2.0, has opened a new sphere of influence to the Patani neojihadist movement, allowing the militants to expand their propaganda campaign to a wider audience, while reaching out to a younger Melayu public. While Jihad 2.0 has presented the resistance movement with new ways to diffuse its message, in a more innovative and appealing manner, it also has enabled it to engage with its audiences more interactively. Because the message is no longer linear, anyone can contribute to the dialectics of the struggle, which in fine results in the alteration and reshaping of its ideological discourse in unprecedented directions. Arguably the ‘glocalisation’ of Islamophobia within Thai culture has resulted in the alteration of the Thai cultural stereotype of the Muslim khaek ‘Other’, transforming the khaek into an evil violent Muslim, both in real and virtual worlds. This further leads to discriminatory attitudes and behaviours towards Muslims, which causes the hardening of the views of the online Patani community of support towards the Thais and possibly its radicalisation.

Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation

Hyperglycemia is a defining feature of Type 1 and 2 diabetes. Hyperglycemia also causes insulin resistance, and our group (Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB. Am J Physiol Endocrinol Metab Endocrinol Metab 290: E471–E479, 2006) has recently demonstrated that hyperglycemia generated by glucose infusion results in insulin resistance after 5 h but not after 3 h. The aim of this study was to investigate possible mechanism(s) by which glucose infusion causes insulin resistance in skeletal muscle and in particular to examine whether this was associated with changes in insulin signaling. Hyperglycemia (∼10 mM) was produced in cannulated male Wistar rats for up to 5 h. The glucose infusion rate required to maintain this hyperglycemia progressively lessened over 5 h (by 25%, P < 0.0001 at 5 h) without any alteration in plasma insulin levels consistent with the development of insulin resistance. Muscle glucose uptake in vivo (44%; P < 0.05) and glycogen synthesis rate (52%; P < 0.001) were reduced after 5 h compared with after 3 h of infusion. Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3β] over the same time course. In isolated soleus strips taken from control or 1- or 5-h glucose-infused animals, insulin-stimulated 2-deoxyglucose transport was similar, but glycogen synthesis was significantly reduced in the 5-h muscle sample (68% vs. 1-h sample; P < 0.001). These results suggest that the reduced muscle glucose uptake in rats after 5 h of acute hyperglycemia is due more to the metabolic effects of excess glycogen storage than to a defect in insulin signaling or glucose transport.

Direct evidence of histopathological impacts of wastewater discharge on resident Antarctic fish (Trematomus bernacchii) at Davis Station, East Antarctica.

During the 2009/2010 summer, a comprehensive environmental impact assessment (EIA) of the wastewater discharge at Davis Station, East Antarctica was completed. As part of this, histological alteration of gill and liver tissue in Antarctic Rock-cod (Trematomus bernacchii) from four sites along a spatial gradient from the wastewater outfall were assessed. All fish within 800 m of the outfall exhibited significant histological changes in both tissues. Common pathologies observed in fish closest to the outfall include proliferation of epithelial cells with associated secondary lamellar fusion in the gills and multifocal granulomata with inflammation and necrosis as well as cysts in the liver. Fish from sites >800 m from the outfall also exhibited alterations but to a lesser degree, with prevalence and severity decreasing with increasing distance from the outfall. This study highlights the value of histopathological investigations as part of EIAs and provides the first evidence of sub-lethal alteration associated with wastewater discharge in East Antarctica.