Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host's rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host's genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.

Fatigue is prominent across many long term physical health conditions. This scoping review aimed to map the fatigue intervention literature, to ascertain if certain interventions may be effective across conditions, and if novel interventions tested in specific long term conditions may be promising for other conditions.

Edible portions of bananas contain high levels of polyphenol oxidase, which catalyzes reactions in the melanin formation pathway. Tyrosine, a physiological substrate of polyphenol oxidase, has an analogous structure to acetaminophen. We investigated whether banana extract causes structural changes in acetaminophen and a decrease in its potency. Acetaminophen concentration in banana extract was measured under different conditions to characterize incompatibility. Reaction products in solution were identified using liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS). Acetaminophen potency decreased with time in the presence of banana extract. The reaction proceeded most efficiently in temperatures 30-37°C and neutral to weakly acidic conditions. Molecular ion peaks derived from the oxidized catechol moiety of acetaminophen were identified in LC/ESI/MS spectra. Our findings suggest that incorporation or simultaneous administration of acetaminophen medication and banana juice may result in decreased efficacy of the clinically important drug. This interaction is likely due to the oxidation of acetaminophen by polyphenol oxidase activity in banana pulp. Therefore, we investigated and characterized a novel interaction between bananas and acetaminophen. To establish a safe and effective antipyretic analgesic regimen using acetaminophen, future studies of this interaction are expected to be performed in humans.

Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection.

Our group originally found and cloned cDNA for a 98-kDa type 1 transmembrane glycoprotein of unknown function. Because of its abundant expression in astrocytes, it was called the protein astroprincin (APCN). Two thirds of the evolutionarily conserved protein is intracytoplasmic, whereas the extracellular domain carries two N-glycosidic side chains. APCN is physiologically expressed in placental trophoblasts, skeletal and hearth muscle, and kidney and pancreas. Overexpression of APCN (cDNA) in various cell lines induced sprouting of slender projections, whereas knockdown of APCN expression by siRNA caused disappearance of actin stress fibers. Immunohistochemical staining of human cancers for endogenous APCN showed elevated expression in invasive tumor cells compared with intratumoral cells. Human melanoma cells (SK-MEL-28) transfected with APCN cDNA acquired the ability of invasive growth in semisolid medium (Matrigel) not seen with control cells. A conserved carboxyterminal stretch of 21 amino acids was found to be essential for APCN to induce cell sprouting and invasive growth. Yeast two-hybrid screening revealed several interactive partners, of which ornithine decarboxylase antizyme-1, NEEP21 (NSG1), and ADAM10 were validated by coimmunoprecipitation. This is the first functional description of APCN. These data show that APCN regulates the dynamics of the actin cytoskeletal and, thereby, the cell shape and invasive growth potential of tumor cells.

Glaucoma is one of the leading causes of visual impairment and blindness worldwide. However, the cause of retinal ganglion cell loss and damage of the optic nerve in its pathogenesis is largely unknown. The high energy demands of these cells may reflect their strong dependence on mitochondrial function and thus sensitivity to mitochondrial defects. To address this issue, we studied whole mitochondrial genome variation in normal tension glaucoma patients and control individuals from the Polish population using next generation sequencing. Our findings indicate that few features of mitochondrial DNA variation are different for glaucoma patients and control subjects. New insights into normal tension glaucoma development are discussed. We provide also a comprehensive approach for mitochondrial DNA analysis and variant evaluation.

The present study investigated the effect of lead (Pb) on bone ultrastructure and chemistry using an in vitro bone model. MC3T3-E1 preosteoblasts were differentiated and treated with lead acetate at 0.4, 2, 10, and 50 μM. No abnormalities in either cell growth or bone nodule formation were observed with the treated dose of lead acetate. However, Pb treatments could significantly increase Pb accumulation in differentiated osteoblast cultures and upregulate expression of Divalent metal transporter 1 (Dmt1) in a dose dependent manner. Pb treatments also altered the expression of osteogenic genes, including secreted phosphoprotein 1, osteocalcin, type I collagen, and osteoprotegerin. Moreover, in mineralized osteoblast cultures, Pb was found to be mainly deposited as Pb salts and oxides, respectively. Ultrastructure analysis revealed Pb localizing with calcium and phosphorus in the mineralized matrix. In mineralizing osteoblast cells, Pb was found in the intracellular calcified vesicles which is one of the bone mineralization mechanisms. Pb was also present in mineral deposits with various shapes and sizes, such as small and large globular or needle-like mineral deposits representing early to mature stages of mineral deposits. Furthermore, Pb was found more in the globular deposits than the needle shaped mineral crystals. Taken together, our observations revealed how Pb incorporates into bone tissue, and showed a close association with bone apatite.

Myocardial infarction (MI) is accompanied with skeletal muscle abnormalities. The aims are to explore an optimal exercise mode to improve cardiac function and prevent skeletal muscle atrophy, and detect the possible mechanisms of exercise-induced inhibition of muscle atrophy.

Dietary restriction (DR) is thought to exert its beneficial effects on healthspan at least partially by a senolytic and senostatic action, i.e. by reducing frequencies of cells with markers of DNA damage and senescence in multiple tissues. Due to its importance in metabolic and inflammation regulation, fat is a prime tissue for health span determination as well as a prime target for DR. We aimed to determine here whether the beneficial effects of DR would be retained over a subsequent period of ad libitum (AL) feeding. Male mice were kept under either 40% DR or AL feeding regimes from 3 to 12 months of age and then either switched back to the opposite feeding regimen or kept in the same state for another 3 months. Visceral adipose tissue from 4 to 5 mice per group for all conditions was analysed for markers of senescence (adipocyte size, γH2A.X, p16, p21) and inflammation (e.g. IL-6, TNFα, IL-1β) using immuno-staining or qPCR. Macrophages were detected by immunohistochemistry. We found that both 9 and 12 months DR (long term) as well as 3 month (short term, mid-life onset) DR reduced the number of cells harbouring DNA damage and adipocyte size (area and perimeter) in visceral adipocytes with similar efficiency. Importantly, beneficial health markers induced by DR such as small adipocyte size and low DNA damage were maintained for at least 3 month after termination of DR, demonstrating that the previously identified 'metabolic memory' of the DR state in male mice extends to senescence markers in visceral fat.

Bird to human transmission of high pathogenicity avian influenza virus (HPAIV) poses a significant risk of triggering a flu pandemic in the human population. Therefore, vaccination of susceptible poultry during an HPAIV outbreak might be the best remedy to prevent such transmissions. To this end, suitable formulations and an effective mass vaccination method that can be translated to field settings needs to be developed. Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. The aim of the present study was to improve the effectiveness of pulmonary vaccination by increasing the vaccine dose deposited in the lungs and by the use of suitable adjuvants. Two adjuvants, namely, Bacterium-like Particles (BLP) and Advax, were spray freeze dried with influenza vaccine into dry powder formulations. Delivery of dry formulations directly at the syrinx revealed that BLP and Advax had the potential to boost either systemic or mucosal immune responses or both. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. Remarkably, all vaccinated animals not only survived a lethal influenza challenge, but also did not show any shedding of challenge virus except for two out of six animals in the Advax group. Overall, our results indicate that passive inhalation is feasible, effective and suitable for mass vaccination of chickens if it can be adapted to field settings.

Macrophage-inducible C-type lectin (Mincle), a pattern recognition receptor, is a critical component of the innate immune system that is involved in the pathogenesis of chronic pain. Previous studies have reported the expression of Mincle in neuronal and glial cells of the brain, but its expression and role in pain processing at the spinal level remain to be determined. The current study was performed to identify Mincle in the spinal cord and to investigate the effect of Mincle activation on spinal sensitization. Most Mincle immunoreactivity was localized within the grey matter and the dorsal and ventral horns of the lumbar spinal cord in naïve rats. A single intrathecal (i.t.) injection of trehalose-6,6-dibehenate (TDB), a Mincle ligand, induced mechanical allodynia. Immunoreactivity to Mincle and Iba-1 in the spinal cord significantly increased after i.t. injection of TDB. Mechanical allodynia was attenuated by daily i.t. injection of minocycline. However, double immunofluorescence revealed that Mincle co-localizes with NeuN (neurons), but not with Iba-1 (microglia) or GFAP (astrocytes). In conclusion, we found that Mincle was present in spinal cord neurons, but not microglia or astrocytes, and may play a role in microglia-induced spinal sensitization.

Collagens are the most abundant vertebrate extracellular matrix proteins. They form a superfamily of 28 members that show a remarkable diversity in molecular and supramolecular organization, tissue distribution and function and mutations in collagen genes result in a wide range of inherited connective tissue diseases. In the recent years, unexpected and very diverse regulatory and mechanical collagen functions have been reported. But the structural and functional landscape of the collagen superfamily is still far from being complete. Zebrafish has emerged over the last decades as a powerful model to interrogate gene function and there are numerous advantages of using zebrafish for collagen research, including recent advances in genome editing technologies and the characterization of the zebrafish matrisome. One can confidently predict that zebrafish will rapidly become a popular vertebrate model to investigate the role of collagens in development, disease and regeneration as discussed in this chapter.

The brain draws on knowledge of statistical structure in the environment to facilitate detection of new events. Understanding the nature of this representation is a key challenge in sensory neuroscience. Specifically, it is unknown whether real-time perception of rapidly-unfolding sensory signals is driven by a coarse or detailed representation of the proximal stimulus history. We recorded electroencephalography brain responses to frequency outliers in regularly-patterned (REG) versus random (RAND) tone-pip sequences which were generated anew on each trial. REG and RAND sequences were matched in frequency content and span, only differing in the specific order of the tone-pips. Stimuli were very rapid, limiting conscious reasoning in favour of automatic processing of regularity. Listeners were naïve and performed an incidental visual task. Outliers within REG evoked a larger response than matched outliers in RAND. These effects arose rapidly (within 80 msec) and were underpinned by distinct sources from those classically associated with frequency-based deviance detection. These findings are consistent with the notion that the brain continually maintains a detailed representation of ongoing sensory input and that this representation shapes the processing of incoming information. Predominantly auditory-cortical sources code for frequency deviance whilst frontal sources are associated with tracking more complex sequence structure.

Cellular communication through chemical synapses is determined by the nature of the neurotransmitter and the composition of postsynaptic receptors. In the excitatory synapse between bipolar and ganglion cells of the retina, postsynaptic AMPA receptors mediate resting activity. During evoked response, however, more abundant and sustained levels of glutamate also activate GluN2B-containing NMDA receptors (NMDARs). This phasic recruitment of distinct glutamate receptors is essential for visual discrimination; however, the fidelity of this basic mechanism under elevated glutamate levels due to aberrant activity, a common pathophysiology, is not known. Here, in both male and female mice with retinal degeneration (rd10), a condition associated with elevated synaptic activity, we reveal that changes in synaptic input to ganglion cells altered both composition and activation of NMDARs. We found that, in contrast to wild type, the spontaneous activity of rd10 cells was largely NMDAR-dependent. Surprisingly, this activity was driven primarily by atypical activation of GluN2A -containing NMDARs, not GluN2B-NMDARs. Indeed, immunohistochemical analyses and Western blot showed greater levels of the GluN2A-NMDAR subunit expression in rd10 retina compared to wild type. Overall, these results demonstrate how aberrant signaling leads to pathway-specific alterations in NMDAR expression and function.

Hyaluronan (HA) and the receptor for hyaluronan-mediated motility (RHAMM) may play an important role in lung development. We examined the expression of HA content and RHAMM during postnatal lung development by analyzing human lung specimens from newborn infants with a variety of lung diseases at different gestational (GA) and postnatal (PNA) ages.

Previous researches have reported that microcystin-LR (MC-LR) contributes to the progression of multiple types of carcinomas including colon cancer; however, the underlying molecular mechanisms remain unclear and require in-depth investigation. Here, the colon cell line DLD-1 was arranged for the analysis by the microRNA microarray which was associated with the cancer metastasis after MC-LR exposure. 31 human microRNAs were differentially expressed, including miR-221, which targeted 3'-UTR of PTEN mRNA and PTEN level was down-regulated by MC-LR treatment. Besides, MC-LR also induced the phosphorylation of STAT3, which can be reversed by adding miR-221 inhibitor and PTEN expression plasmid. Furthermore, miR-221 inhibitor, STAT3 siRNA and PTEN expression plasmid could reverse the effects of MC-LR induced migration with the accumulation of β-catenin in nuclei. In conclusion, our study suggested that MC-LR promoted the progression of colon carcinoma, at least in part, by regulating the expression miR-221, PTEN and STAT3 phosphorylation, which offers a novel perspective to understand the connection between MC-LR and colon cancer.

Dihalobenzoquinones are a group of disinfection byproducts with high potential toxicity and thus currently receiving increased attention. A determination method of 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) and 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ) was developed upon using liquid-liquid extraction and a gas chromatography with an electronic capture detector (LLE-GC-ECD). The optimized extraction condition was as the following: volume ratio of formic acid to water 0.005%, Na2SO4 dosage 200 g L-1, methyl-tert-butyl ether (MtBE)/water volume ratio 1/10, and extraction with MtBE for once. With the dosed concentrations of 0.5-5.0 μg L-1, the recovery rates of 2,6-DCBQ and 2,6-DBBQ were 81%-88% and 73%-96%. The limits of quantitation (LOQs) of the LLE-GC-ECD method were 2.4 and 2.7 ng L-1 in 1-L water for 2,6-DCBQ and 2,6-DBBQ. In six local tap waters, 2,6-DCBQ was detected in the range of

To assess the safety and efficacy of percutaneous short-segment pedicle instrumentation compared with conventionally open short-segment pedicle instrumentation and provide recommendations for using these procedures to treat thoracolumbar fractures.

Intraoperative systemic esmolol has been shown to reduce postsurgical pain. Nonetheless, it is unknown whether the use of intraoperative systemic esmolol can improve patient-reported postsurgical quality of recovery. The main objective of the current investigation was to evaluate the effect of intraoperative esmolol on postsurgical quality of recovery. We hypothesized that patients receiving intraoperative esmolol would report better quality of postsurgical recovery than the ones receiving saline.

This review aims to evaluate the effectiveness and safety of acupuncture treatment for patients with whiplash-associated disorder (WAD).