718 research outputs found

    Hong Kong, China, and the Disruption of Antitrust

    Get PDF
    Under the “One Country, Two Systems” rule, Hong Kong and China maintain different legal systems. This dichotomy also applies in the antitrust context. China adopted its Anti-Monopoly Law in 2007, while Hong Kong waited until 2012 to introduce its Competition Ordinance (and another three years to fully implement it). This article compares the antitrust laws of these two jurisdictions and their enforcement in light of a turning point: the disruption caused by Big Tech. Interestingly, while the competition laws of Hong Kong and China are substantively similar to each other and to legal precedent in other jurisdictions, Hong Kong has adopted an adversarial system of enforcement, and China an administrative system. Through an analysis of recent antitrust developments in the two jurisdictions, this article shows the importance of agency independence, due process, and robust judicial scrutiny for the proper functioning of an administrative system of enforcement. This article also demonstrates that judicial scrutiny in an adversarial system needs the certainty of legal rules, particularly to clarify the burden of proof to be met by the competition authorities. In light of these findings, this article proposes a three-pronged competition and regulation approach for the scrutiny of Big Tech that does not water down the two principles of due process and robust judicial scrutiny. This is significant. The frustration with market concentration should not lead policymakers to propose changes to antitrust enforcement that could weaken these two principles and attribute a higher value to the speed of decision-making over the importance of a thorough analysis

    The Role of Esterification on Detection of Protonated and Deprotonated Peptide Ions in Matrix Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry (MS)

    Get PDF
    Esterification was used to investigate how introduction of aliphatic chains within the peptide structure affects the MALDI response of ions analyzed in both polarity regimes. In binary mixtures containing equimolar amounts of a peptide with its correspondent alkyl ester, derivatization of the carboxylic groups has the tendency to increase MALDI detection of the modified protonated peptide ions. This positive effect on ion yield is more pronounced when longer alcohols are employed. In negative mode, the situation is antithetic and esterification produces a deleterious effect on the ion yield of the corresponding deprotonated species. From the data reported here we postulate that modifications of the acidic character of peptides prevent formation of anionic species under MALDI analysis. Furthermore, suppression of the formation pathway for anions alters the overall number of molecules which can undergo protonation. This results in an increased ion yield for the protonated esters

    Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows

    Get PDF
    The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as \ue2\u80\u9cproduction diseases\ue2\u80\u9c, such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. Biological significance: For high-yielding dairy cows there are several \ue2\u80\u9coccupational diseases\ue2\u80\u9c that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene expression, i.e. transcriptomics. For extending the knowledge towards the proteome and the metabolome, the respective technologies are of increasing importance and can provide an overall view of how dairy cows react to metabolic stress, which is needed for an in-depth understanding of the molecular mechanisms of the related diseases. We herein review the current findings from studies applying proteomics and metabolomics to transition-related diseases, including fatty liver, ketosis, endometritis, hypocalcaemia and laminitis. For each disease, a brief overview of the up to date knowledge about its pathogenesis is provided, followed by an insight into the most recent achievements on the proteome and metabolome of tissues and biological fluids, such as blood serum and urine, highlighting potential biomarkers. We believe that this review would help readers to be become more familiar with the recent progresses of molecular background of transition-related diseases thus encouraging research in this field

    Platelet aggregation studies: autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count

    Get PDF
    Adjusting platelet count (PC) in platelet-rich plasma (PRP) using platelet-poor plasma (PPP) is recommended for platelet aggregation (PA) studies, but it could also affect PA independently of the decrease in PC. Analysis of aggregation tracings from healthy controls showed that PC correlated with PA in 47 diluted-PRPs, but not in 104 undiluted-PRPs. Dilution of 9 PRPs with PPP progressively decreased PA, while dilution of washed platelets with buffer hardly affected PA. Apyrase partially prevented the inhibitory effect of PPP. Therefore, the practice of diluting PRP with PPP to adjust platelet count should be avoided because it artefactually inhibits PA

    Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array (MEA) recording study.

    Get PDF
    The dynamic equilibrium between glutamate- and GABA-mediated synaptic neurotransmission in the brain is fundamental to the control of nervous system function. Such a balance is regulated by the \u2018tonic\u2019 release of a variety of neurotransmitters and endogenous factors that influence synaptic function. One such important group of modulatory molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in-vivo physiologically relevant concentrations, the effects of these two classes of GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA) recording technique and a novel method of analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect novel drug-induced network up-states (burst). We found that the NSs tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) applied at low nanomolar concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 \ub5M), both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after washout, the excitability of inhibitory neurons continued to be depressed, leading to a network long term depression (LTD). The BDZs clonazepam (CLZ) and midazolam (MDZ) also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN), an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex-vivo neuronal networks show a sensitivity to drugs comparable to that expressed in vivo, but also provide a new global in-vitro description of the physiological mode of action of NSs and BDZs that can help in understanding their activity in more complex systems

    Biobanking in the Year 2007

    Get PDF
    Biobanking is an emerging specialty in which competencies in cellular and molecular biology, medicine, genetics, cryobiology, bioengineering, information technology and ethics merge into a servic

    Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks

    Get PDF
    Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS). Simultaneously, an atypical “seizure-like” neuronal network activity was recorded by multi-electrode array (MEA) electrophysiology. These effects were prevented by minocycline, an established anti-inflammatory antibiotic. We show here that the same inhibitory effect against LPS-induced neuroinflammation is exerted also by natural plant compounds, polyphenols, such as curcumin (CU, curcuma longa), crocin (CR, saffron), and resveratrol (RE, grape), as well as by the glucagon like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4). The drugs tested also caused per-se early transient (variable) changes of network activity. Since it has been reported that LPS-induced neuroinflammation causes rearrangements of glutamate transporters in astrocytes and microglia, we suggest that neural activity could be putatively increased by an imbalance of glial glutamate transporter activity, leading to prolonged synaptic glutamatergic dysregulation

    Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas

    Get PDF
    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations

    Widespread extrahepatic expression of acute-phase proteins in healthy chicken (Gallus gallus) tissues

    Get PDF
    Acute phase proteins (APP) are plasma proteins that can modify their expression in response to inflammation caused by tissue injury, infections, immunological disorders or stress. Although APP are produced mainly in liver, extrahepatic production has also been described. As a prerequisite to get insight the expression of APP in chicken during diseases, this study investigated the presence of five APP, including alpha1-acid glycoprotein (AGP), Serum Amyloid A (SAA), PIT54, C-Reactive protein (CRP) and Ovotransferrin (OVT) in twenty tissues collected from healthy chicken (Gallus gallus) by quantitative Real Time PCR and immunohistochemistry. As expected, APP gene abundance was higher in liver compared with other tissues. The mRNA coding for CRP, OVT and SAA was detected in all analyzed tissues with a higher expression in gastrointestinal tract, respiratory and lymphatic samples. SAA expression was particularly high in cecal tonsil, lung, spleen and Meckel's diverticulum, whereas OVT in lung, bursa of Fabricius and pancreas. AGP and PIT54 mRNA expression were detected in all tissues but at negligible levels. Immunohistochemical expression of AGP and OVT was variably detected in different organs, being identified in endothelium of every tissue. Positive cells were present in the epithelium of the mucosal layer of gastrointestinal tract and kidney. Lung and central nervous system stained for both proteins. No positive staining was detected in lymphoid tissues and muscle. These results suggest that most tissues can express different amount of APP even in healthy conditions and are therefore capable to mount a local acute phase reaction

    Evaluation of quantity and purity of miRNAs extracted from different matrices collected from dogs with Mast Cell Tumours.

    Get PDF
    MicroRNAs (miRNAs) are a class of short non-coding RNA, which interact with the 3’ UTR region of complementary mRNA to decrease or inhibit the translation of proteins (Lai, 2002). MiRNAs regulate pathways in various pathophysiological status, and are regarded as biomarkers for early diagnosis of several diseases, including cancer (Di Leva et al., 2014).The study aims to evaluate the quality and purity of miRNAs extracted from a) 11 archival Formalin Fixed and Paraffin Embedded (FFPE) samples of Mast Cell Tumour (MCT) at stage I, II, III and IV, and 8 intra-patient healthy controls; b) samples collected during surgery, including 6 samples of saliva, primary tumour biopsy and serum/plasma. The quality of miRNA largely influence the downstream experiments, and must be carefully evaluated before performing for examples, the sequencing reaction. MiRNA extraction was carried out using commercial kits (Qiagen) and quantify using Small RNA Kit (Agilent) on Agilent 2100 Bioanalyzer. The results showed that the concentration of miRNAs from FFPE, saliva,  primary tumor biopsy and serum was acceptable with a Median (Me)= 56,91 ng/ml, Me=10,30 ng/ml, Me=3,44 ng/ml and  Me=0,71 ng/ml, and a miRNA/Small RNA ratio of 48%, 61%, 17% and 76%, respectively. The concentration of miRNAs from plasma was not detectable. Studies reveal that plasma ranks as the first choice source for diagnostic purpose, much more than serum (Aung et al., 2014), but the debate remains open and subsequent analyses are needed.The concentration of miRNAs from FFPE and saliva samples is higher than that from other matrices. Possible explanations include a) different quantity and quality of starting materials; b) nucleic acids fragmentation, due to the formalin fixation and paraffin embedded procedure; c) presence of nucleases in saliva, which produce small fragments recognized as miRNAs or smallRNAs.In conclusion, the quantity and the purity of miRNAs, obtained using Qiagen commercial kits, are reliable for further NGS analysis
    corecore