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Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy. [ABSTRACT FROM AUTHOR]

This study investigates the role of the country- and firm-level governance practices on the relationship between excess-cash and firm value in ASEAN-5 markets. Using the Generalized Method of Moment models and a sample of 578 firms from 2010 to 2020 the study finds that excess-cash reduces firm value, indicating high agency costs and low firm value. However, excess-cash motivated by managerial ownership, founder CEO, board independence, shareholder rights and creditor rights increase firm value while excess-cash due to managerial entrenchment and CEODuality reduce firm value. In the sub-sample analyses the study finds that entrenched managers and board size play a less effective role in wasting excess-cash in low-excess-cash firms while independent directors play a higher monitoring role in high-excess-cash firms. In addition, governance at the country-level is more effective than at the firm-level in improving the value of excess-cash in large firms. The study offers unique evidence on the relationship between excess-cash and firm value by integrating corporate governance practices at the firm- and country-levels. The research aids practitioners, academics, policymakers and investors in developing the best liquidity policies to enhance business performance.

Background and purpose: Recent evidence suggests that N6, 2'-O-dimethyladenosine (m6Am) modifying enzyme phosphorylated C-terminal domain-interacting factor 1 (PCIF1) may be an important biomarker/therapeutic target in gastric cancer. However, the relationship between this novel PCIF1 molecular mechanism and gastric cancer progression remains to be further explored. In this study, we analyzed the regulatory role of PCIF1 on gastric cancer proliferation, migration and invasion and the mechanism of its regulatory target gene ACOT8 in gastric cancer progression. Methods: PCIF1 expression in gastric cancer and non-gastric cancer tissues of gastric cancer patients was analyzed using Gene Expression Profile Interaction Analysis (GEPIA), and the correlation of PCIF1 expression with overall survival in gastric cancer patients was analyzed. We collected all gastric cancer tissues and matched para-cancerous tissues from 89 primary gastric cancer patients treated in Department of Gastroenterology of Changsha First Hospital from 2019 to 2021. PCIF1 expression was analyzed by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. In in vitro experiments, SNU5 cells were divided into PCIF1 knockdown (sh-PCIF1) group and corresponding control (sh-NC) group, and AGS cells were divided into vehicle as normal control (NC) group and PCIF1 overexpression (PCIF1) group. The effect of PCIF1 on gastric cancer cell proliferation, invasion and migration was investigated using cell counting kit-8 (CCK-8), EdU and transwell assays. Furthermore, ACOT8 expression was knocked down in PCIF1-overexpressing AGS cells, and rescue experiments were performed. A subcutaneous xenograft model was used to determine the biological effects of PCIF1 in gastric cancer in vivo. Results: PCIF1 expression was abnormally high in gastric cancer tissues and cell lines, with significant correlation between PCIF1 expression and the prognosis of gastric cancer patients. Compared with the sh-NC group, the cell viability, EdU positive cells, migration and invasion cell numbers in the sh-PCIF1 group were significantly decreased (P＜0.05). Compared with the NC group, the cell viability, EdU positive cells, migration and invasion cell numbers in the PCIF1 group were significantly increased (P＜0.05). In PCIF1-overexpressing AGS cells, knockdown of ACOT8 expression decreased cell viability, EdU-positive cells and migrating and invasive cell numbers. In vivo experiments showed, compared with the NC group, the tumor volume and weight of the nude mice in the PCIF1-overexpressing group were significantly increased (P＜0.05). Conclusions: PCIF1 is upregulated in gastric cancer cell lines and tissues. In addition, the PCIF1/ACOT8 axis is involved in mediating the malignant behavior of gastric cancer cells. [ABSTRACT FROM AUTHOR]

Background: BSG (CD147) is a member of the immunoglobulin superfamily that shows roles for potential prognostics and therapeutics for metastatic cancers and SARS-CoV-2 invasion for COVID-19. The susceptibility of malignant cancers to SARS-CoV-2 as well as the correlations between disease outcome and BSG expression in tumor tissues have not been studied in depth. Methods: In this study, we explored the BSG expression profile, survival correlation, DNA methylation, mutation, diagnostics, prognostics, and tumor-infiltrating lymphocytes (TILs) from different types of cancer tissues with corresponding healthy tissues. In vitro studies for cordycepin (CD), N6-(2-hydroxyethyl) adenosine (HEA), N6, N6-dimethyladenosine (m62A) and 5′-uridylic acid (UMP) on BSG expression were also conducted. Results: We revealed that BSG is conserved among different species, and significantly upregulated in seven tumor types, including ACC, ESCA, KICH, LIHC, PAAD, SKCM and THYM, compared with matched normal tissues, highlighting the susceptibility of these cancer patients to SARS-CoV-2 invasion, COVID-19 severity and progression of malignant cancers. High expression in BSG was significantly correlated with a short OS in LGG, LIHC and OV patients, but a long OS in KIRP patients. Methylation statuses in the BSG promoter were significantly higher in BRCA, HNSC, KIRC, KIRP, LUSC, PAAD, and PRAD tumor tissues, but lower in READ. Four CpGs in the BSG genome were identified as potential DNA methylation biomarkers which could be used to predict malignant cancers from normal individuals. Furthermore, a total of 65 mutation types were found, in which SARC showed the highest mutation frequency (7.84%) and THYM the lowest (0.2%). Surprisingly, both for disease-free and progression-free survival in pan-cancers were significantly reduced after BSG mutations. Additionally, a correlation between BSG expression and immune lymphocytes of CD56bright natural killer cell, CD56dim natural killer cell and monocytes, MHC molecules of HLA-A, HLA-B, HLA-C and TAPBP, immunoinhibitor of PVR, PVRL2, and immunostimulators of TNFRSF14, TNFRSF18, TNFRSF25, and TNFSF9, was revealed in most cancer types. Moreover, BSG expression was downregulated by CD, HEA, m62A or UMP in cancer cell lines, suggesting therapeutic potentials for interfering entry of SARS-CoV-2. Conclusions: Altogether, our study highlights the values of targeting BSG for diagnostic, prognostic and therapeutic strategies to fight malignant cancers and COVID-19. Small molecules CD, HEA, m62A and UMP imply therapeutic potentials in interfering with entry of SARS-CoV-2 and progression of malignant cancers. [ABSTRACT FROM AUTHOR]

T cells engineered to express HIV-specific chimeric antigen receptors (CARs) represent a promising strategy to clear HIV-infected cells, but to date have not achieved clinical benefits. A likely hurdle is the limited T cell activation and persistence when HIV antigenemia is low, particularly during antiretroviral therapy (ART). To overcome this issue, we propose to use a cytomegalovirus (CMV) vaccine to stimulate CMV-specific T cells that express CARs directed against the HIV-1 envelope protein gp120. In this study, we use a GMP-compliant platform to engineer CMV-specific T cells to express a second-generation CAR derived from the N6 broadly neutralizing antibody, one of the broadest anti-gp120 neutralizing antibodies. These CMV-HIV CAR T cells exhibit dual effector functions upon in vitro stimulation through their endogenous CMV-specific T cell receptors or the introduced CARs. Using a humanized HIV mouse model, we show that CMV vaccination during ART accelerates CMV-HIV CAR T cell expansion in the peripheral blood and that higher numbers of CMV-HIV CAR T cells were associated with a better control of HIV viral load and fewer HIV antigen p24+ cells in the bone marrow upon ART interruption. Collectively, these data support the clinical development of CMV-HIV CAR T cells in combination with a CMV vaccine in HIV-infected individuals.

COVID-19 is an acute respiratory disease caused by SARS-CoV-2 that has spawned a worldwide pandemic. ADAM17 is a sheddase associated with the modulation of the receptor ACE2 of SARS-CoV-2. Studies have revealed that malignant phenotypes of several cancer types are closely relevant to highly expressed ADAM17. However, ADAM17 regulation in SARS-CoV-2 invasion and its role on small molecules are unclear. Here, we evaluated the ADAM17 inhibitory effects of cordycepin (CD), thymoquinone (TQ), and N6, N6-dimethyladenosine (m62A), on cancer cells and predicted the anti-COVID-19 potential of the three compounds and their underlying signaling pathways by network pharmacology. It was found that CD, TQ, and m62A repressed the ADAM17 expression upon different cancer cells remarkably. Moreover, CD inhibited GFP-positive syncytia formation significantly, suggesting its potential against SARS-CoV-2. Pharmacological analysis by constructing CD-, TQ-, and m62A-based drug-target COVID-19 networks further indicated that ADAM17 is a potential target for anti-COVID-19 therapy with these compounds, and the mechanism might be relevant to viral infection and transmembrane receptors-mediated signal transduction. These findings imply that ADAM17 is of potentially medical significance for cancer patients infected with SARS-CoV-2, which provides potential new targets and insights for developing innovative drugs against COVID-19. [ABSTRACT FROM AUTHOR]

ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20-009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression. [ABSTRACT FROM AUTHOR]

The use of broadly neutralizing antibodies (bNAbs) is a promising approach to HIV-1 treatment. In this work, we evaluate the neutralizing activity of the following HIV-1 bNAbs: VCR07-523, N6, PGDM1400, CAP256-VRC26.25, 10-1074, PGT128, 10E8, and DH511.11P, which are directed to different Env surface epitopes. We used the global panel of HIV-1 pseudoviruses to analyze the bNAbs' potency and chose the most potent ones. To achieve maximum neutralization breadth and minimum IC50 concentration, the most effective antibodies were tested in double and triple combinations. Among the doubles, the combinations of N6+PGDM1400 and N6+PGT128 with IC50 ≤ 0.3 µg/mL proved to be the most effective. The most effective triple combination was N6+PGDM1400+PGT128. Our data demonstrate that this combination neutralizes pseudoviruses of the global HIV-1 panel with IC50 ≤ 0.11 µg/mL and IC80 ≤ 0.25 µg/mL. [ABSTRACT FROM AUTHOR]

Influenza A viruses are a diverse species that include 16 true hemagglutinin (HA) subtypes and 9 true neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 subtype NAs are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties in vitro and in vivo and mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding to the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 mouse challenge models when the antibodies were given prophylactically. [ABSTRACT FROM AUTHOR]

Influenza A viruses are a diverse species that include 16 true hemagglutinin (HA) subtypes and 9 true neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 subtype NAs are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties in vitro and in vivo and mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding to the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 mouse challenge models when the antibodies were given prophylactically.

بهینه­سازی کشت بافت برای فرآیند انتقال ژن و تهیه گیاهان عاری از بیماری باکتریایی و ویروسی لازم و ضروری است. این آزمایش به‌صورت فاکتوریل در قالب طرح کاملاً تصادفی با 3 تکرار در آزمایشگاه بیوتکنولوژی دانشکده کشاورزی دانشگاه شهید مدنی آذربایجان در سال 1395 انجام گرفت. در گندم از ریزنمونه‌های مختلفی نظیر گل‌آذین، جنین نارس و جنین بالغ برای کشت بافت استفاده‌ شده است. یکی از معایب مهم گیاهان تک­لپه­ای این است که وقتی از جنین بالغ به‌­عنوان ریزنمونه استفاده می­شوند فراوانی باززایی از کالوس در مقایسه با جنین­های نابالغ کاهش می­یابد. در این آزمایش برای باززایی گیاه گندم از دو نوع محیط کشت MS و N6 و از هورمون­های اکسینی و سیتوکینی متفاوت روی ریزنمونه­های کولئوپتیلی استفاده شد. ارزیابی نتایج نشان داد که بهترین ژنوتیپ برای باززایی C-D-9 و در بین هورمون­های سیتوکینی مختلف بهترین هورمون BAP حاوی 2 میلی‌گرم در لیتر و در بین هورمون­های مختلف اکسینی بیش­ترین باززایی در محیط کشت حاوی 1میلی­گرم در لیتر IAA به­همراه 1میلی­گرم در لیتر BAبه دست آمد. در محیط کشت­های مختلف MS، بالاترین میزان باززایی مربوط به محیط کشت MS(3) و در محیط کشت مختلف N6 بالاترین میزان باززایی مربوط به محیط کشت N6(3) بود. مقایسه محیط کشت MS با N6 در باززایی لاین­ها گندم نشان داد که محیط کشت MS نسبت به N6 بهتر عمل می­کند.

This dataset comprises the characterizations, tribological and thermal properties of Silicon carbide (SiC) reinforced Nylon 6 (N6) or Polyamide 6 composites. The dataset illustrates the tribological properties such as coefficient of friction, wear and it also describes the characterizations and thermal stability of polyamide composites by varying the weight percentages from 5 - 30wt.% The composites samples were fabricated by injection moulding method. The tribological, characterization and thermal behaviors were determined by wear test, characterizations were carried out by Scanning Electron Microscope (SEM) and Fourier Transform Infrared (FTIR), Thermal stability, degradation performed by Thermogravimetric Analysis (TGA) and Derivative Thermogravimetry (DTG) of the polyamide composites. The dataset helps the readers to understand the significant characteristics of the SiC reinforced N6 composites. However, it is revealed that the addition of SIC can enhance the N6 properties. The preparation of N6 polymer composites findings were useful with good tribological (highly wear resistive) and thermal stability characteristics. This composite can be used for high impact stress parts of gears application.

Copyright of Mustafa Kemal University Journal of Agricultural Sciences / Mustafa Kemal Üniversitesi Tarım Bilimleri Dergisi is the property of Mustafa Kemal University, Faculty of Agriculture and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Edwardsiella tarda can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against E. tarda was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against E. tarda were 1.29–3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of E. tarda and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 μg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by E. tarda, superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against E. tarda infections.

RNA modifications have generated much interest in the virology field, as recent works have shown that many viruses harbor these marks and modify cellular marks. The most abundant mRNA modification in eukaryotic cells, N6-methyladenosine (m6A), has been examined extensively at the genome-wide scale in both cellular and viral contexts. This Gem discusses the role of m6A in gene regulation and describes recent advancements in Kaposi's sarcoma-associated herpesvirus (KSHV) and simian virus 40 (SV40) research. We provide insights into future research related to m6A in DNA viruses. [ABSTRACT FROM AUTHOR]

Several subtypes of avian influenza viruses (AIVs) are emerging as novel human pathogens, and the frequency of related infections has increased in recent years. Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral drugs available for therapeutic intervention for AIV-infected patients, studies on NAI resistance among AIVs have been limited, and markers of resistance are poorly understood. Previously, we identified unique NAI resistance substitutions in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA subtypes using genefragmented random mutagenesis. We generated libraries of mutant influenza viruses using reverse genetics (RG) and selected resistant variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were introduced into each NA gene for comparison. We identified 37 amino acid substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4 in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or peramivir) as determined using a fluorescence-based NA inhibition assay. Substitutions conferring NAI resistance were mainly categorized as either novel NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate that each NA subtype possesses unique NAI resistance markers, and knowledge of these substitutions in AIVs is important in facilitating antiviral susceptibility monitoring of NAI resistance in AIVs. [ABSTRACT FROM AUTHOR]

One of the major issues in manufacturing systems is to determine how to deal effectively with unexpected disruption during production operation, (e.g. material unavailability, machine breakdown, employee absenteeism, power failure and additional resources, etc.). This paper presents a comprehensive literature review which shows that existing methods and tools offer very few concepts that are sufficient to handle a variety of random disruptions in manufacturing industries. A scheduling model was developed, and random sampling and simulation runs were done to minimise instability of the production system after random disruption. The results indicate that the degree of failure in the production line fluctuates and additional resources are required in order to meet up with planned demand. [ABSTRACT FROM PUBLISHER]

Copyright of Ensayos Sobre Política Económica is the property of Banco de la Republica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper documents industrial output growth around the poor periphery (Latin America, the European periphery, the Middle East and North Africa, Asia, and sub-Saharan Africa) between 1870 and 2007. We find that although the roots of rapid peripheral industrialization stretch into the late 19th century, the high point of peripheral industrialization was the 1950-1973 period, which saw widespread import-substituting industrialization. This period was also the high point of unconditional industrial catching up, defined as the tendency of less industrialized countries to post higher per capita manufacturing growth rates, and which occurred between 1920 and 1990. [ABSTRACT FROM AUTHOR]

Translation is a fundamental process in all living organisms that involves the decoding of genetic information in mRNA by ribosomes and translation factors. The dysregulation of mRNA translation is a common feature of tumorigenesis. Protein expression reflects the total outcome of multiple regulatory mechanisms that change the metabolism of mRNA pathways from synthesis to degradation. Accumulated evidence has clarified the role of an increasing amount of mRNA modifications at each phase of the pathway, resulting in translational output. Translation machinery is directly affected by mRNA modifications, influencing translation initiation, elongation, and termination or altering mRNA abundance and subcellular localization. In this review, we focus on the translation initiation factors associated with cancer as well as several important RNA modifications, for which we describe their association with cancer.

This study examines the nature and consequences of China's rise to the center of world economic affairs through manufacturing-led development. Our historical analysis shows that China is still well short of the point in its developmental process where its growth might be reasonably expected to slow, or the energy, resource and carbon intensity of growth to recede. The study argues that the current trajectory of industrialization will have to be altered when China becomes more actively engaged in dealing with structural issues at home and abroad against the background of the unwinding of global imbalances. One profitable strategy that China might employ would be to approximate the incredibly fruitful mass-market integration efforts of the USA that eventually elevated it to its position of global primacy. The cyclical re-emergence of excess capacity in Chinese heavy industry, serious questions about the medium term ability of other major regions to accommodate further large gains in Chinese market share, and the stark conflict between the contemporary style of industrial development and the health of the biosphere indicate strongly that now is the time to catalyze the required adjustment and reform processes that will underpin sustainable long-run prosperity. [ABSTRACT FROM AUTHOR]

Abstract: Biochemical modifications of tau proteins have been proposed to be among the earliest neurobiological changes in Alzheimer''s disease (AD) and correlate better with cognitive symptoms than do beta-amyloid plaques. We have recently reported that adenovirus-mediated overexpression of the NH2 26–230aa tau fragment evokes a potent NMDA-mediated neurotoxic effect in primary neuronal cultures. In order to assess whether such N-terminal tau fragment(s) are indeed produced during apoptosis or neurodegeneration in vivo, we attempted to ascertain their presence in cell and animal models using an anti-tau antibody directed against the N-terminal sequence of human protein located downstream of the caspase(s)-cleavage site DRKD25-QGGYTMHQDQ. We provide biochemical evidence that a caspase(s)-cleaved NH2-terminal tau fragment of 20–22 kDa, consistent with the size of the NH2 26–230aa neurotoxic fragment of tau, is generated in vitro in differentiated human SH-SY5Y cells undergoing apoptosis by BDNF withdrawal or following treatment with staurosporine. In addition this NH2-terminally cleaved tau fragment, whose expression correlates with a significant up-regulation of caspase(s) activity, is also specifically detected in vivo in the hippocampus of 15 month-old AD11 transgenic mice, a model in which a progressive AD-like neurodegeneration is induced by the expression of transgenic anti-NGF antibodies. The results support the idea that aberrant activation of caspase(s), following apoptotic stimuli or neurodegeneration insults, may produce one or more toxic NH2 tau fragments, that further contribute to propagate and increase cellular dysfunctions in AD. [Copyright &y& Elsevier]

Was the average late nineteenth century Canadian manufacturer a hopelessly inefficient laggard when compared to his American counterparts just on the other side of the international border? Could it have been that Canadian producers were really productivity leaders so early in their industrialization process? To answer these fundamental questions about the performance of a small open economy at a key juncture in its industrial development we need a quantitative comparison of Canadian relative to US productivity. Unfortunately, the approach we adopt with respect to data compilation, methodological choice, and the identification of inputs, outputs, input weights, and prices has both quantitative and qualitative effects on any performance assessment we may undertake. To illustrate the severity of these effects we use manuscript census data from 1870/1871 to derive a series of total factor productivity (TFP) comparisons for a sample of manufacturing establishments located immediately to the north and south of the Canada–US border. Even with some of the most common and defensible variable definitions, we find dramatic differences between the most optimistic and most pessimistic assessments of late nineteenth century Canadian performance. Our case study suggests to us that those interested in the assessment of long run performance differentials should appreciate the sensitivity of these assessments and they should carefully consider the approach that has been taken toward data preparation, methodological choice, and variable definitions in their construction. [ABSTRACT FROM AUTHOR]

This paper presents time series of tariff rates in Australia from the time of Federation. As a preliminary to the construction of economy-wide series, it constructs series for three broadly representative goods throughout the 100 years: passenger motor vehicles, blankets, and beer. It then constructs two economy-wide series, one for all imports and another for dutiable imports only. It discusses the main events relating to turning points in the series and concludes with some applications. [ABSTRACT FROM AUTHOR]

Abstract: The cerebellum is involved in complex physiological functions including motor control, sensory perception, cognition, language, and emotion. Humans and animals with prion diseases are characterized clinically by ataxia, postural abnormalities and cognitive decline. Pathology in the cerebellum affected by prions includes spongiform degeneration, neuronal loss, and gliosis. To develop an in vitro model system for studying prion biology in cerebellar cells, we established and characterized an immortal cell line (CRBL) isolated from the cerebellum of mice lacking expression of a protein involved in cell cycle arrest. The characteristics of the cells include morphological heterogeneity, rapid proliferation, serum responsiveness during growth, and a change in the number of chromosomes. CRBL cells expressed both neuronal and glial cell markers as well as a considerable level of cellular prion protein, PrPC. Upon in vitro infection, CRBL cells exhibited selective susceptibility to prions isolated from different sources. These cells chronically propagated prions from SMB cells. Strain-specific prion infection in CRBL cells was not due to instability of the cell line, allelic variance, or mutations in the PrP gene. Molecular properties of prions derived from SMB cells were maintained in the infected CRBL cells. Our results suggest that the specific interaction between a prion strain and hosts determined the selective susceptibility of CRBL cells, which reflects the conditions in vivo. In addition to the future studies revealing cellular and molecular mechanism involved in prion pathogenesis, CRBL cells will contribute to the studies dealing with prion strain properties and host susceptibilities. [Copyright &y& Elsevier]

XPS measurements of nylon 6 recorded with a SSX-100 spectrometer in standardized experimental conditions are presented: survey scan, high resolution core level spectra as well as the energy loss regions of carbon, oxygen, and nitrogen peaks are analyzed. This is part of a contract work aiming to record spectra in the very same conditions of some forty different polymers. © 2006 American Vacuum Society. [ABSTRACT FROM AUTHOR]

Abstract: Estradiol-17ß-d-glucuronide (E217G) and taurolithocholate (TLC) induce acute cholestasis-associated with retrieval of the bile salt export pump (Bsep), which parallels with alteration in transport activity. cAMP stimulates the apically directed vesicular trafficking of transporters, partially preventing these alterations. The hepatoprotector, silymarin, which inhibits cAMP-phosphodiesterase, prevents the cholestasis induced in vivo by both estrogens and TLC. We aimed to assess the ability of silibinin (Sil), the silymarin active component, to prevent the retrieval of Bsep induced by TLC and E217G, and the associated alteration in its transport function. The possible involvement of cAMP as a second messenger and the intracellular signalling pathways implicated were also evaluated. Functional studies were performed analysing the proportion of isolated rat hepatocyte couplets (IRHC) accumulating the fluorescent bile salt analogue, cholyl-lysylfluorescein (CLF), into their sealed canalicular vacuoles. Cellular localisation of Bsep was assessed by immunofluorescent staining. Intracellular levels of cAMP were measured by ELISA. Sil (2.5μM) elevated by 40±3% intracellular cAMP, and mimicked the ability of dibutyryl-cAMP (10μM) to prevent internalisation of Bsep and the TLC (2.5μM)- and E217G (50μM)-induced impairment in the capacity of IRHC to accumulate CLF apically. Preventive effects of Sil and dibutyryl-cAMP were not abolished by the specific protein kinase A inhibitors, KT5720 and H89. Contrarily, the intracellular Ca2+ chelator, BAPTA/AM, significantly blocked the protective effect of both compounds. We conclude that Sil prevented TLC- and E217G-induced bile salt secretory failure, at least in part, by avoiding redistribution of Bsep, by a mechanism probably involving cAMP-induced cytosolic Ca2+ elevations. [Copyright &y& Elsevier]

The pur6 gene of the puromycin biosynthetic gene (pur) cluster from Streptomyces alboniger is shown to be essential for puromycin biosynthesis. Cell lysates from this mycelial bacterium were active in linking l-tyrosine to both 3′-amino-3′-deoxyadenosine and N6,N6-dimethyl-3′-amino-3′-deoxyadenosine with a peptide-like bond. Identical reactions were performed by cell lysates from Streptomyces lividans or Escherichia coli transformants that expressed pur6 from a variety of plasmid constructs. Physicochemical and biochemical analyses suggested that their products were tridemethyl puromycin and O-demethylpuromycin, respectively. Therefore, it appears that Pur6 is the tyrosinyl-aminonucleoside synthetase of the puromycin biosynthetic pathway. [Copyright &y& Elsevier]

The phosphorylated RNA polymerase II CTD interacting factor 1 (PCIF1) is a methyltransferase that adds a methyl group to the N6-position of 2'O-methyladenosine (A m ), generating N6, 2'O-dimethyladenosine (m 6 A m ) when A m is the cap-proximal nucleotide. In addition, PCIF1 has ancillary methylation activities on internal adenosines (both A and A m ), although with much lower catalytic efficiency relative to that of its preferred cap substrate. The PCIF1 preference for 2'O-methylated A m over unmodified A nucleosides is due mainly to increased binding affinity for A m . Importantly, it was recently reported that PCIF1 can methylate viral RNA. Although some viral RNA can be translated in the absence of a cap, it is unclear what roles PCIF1 modifications may play in the functionality of viral RNAs. Here we show, using in vitro assays of binding and methyltransfer, that PCIF1 binds an uncapped 5'-A m oligonucleotide with approximately the same affinity as that of a cap analog (K M  = 0.4 versus 0.3 μM). In addition, PCIF1 methylates the uncapped 5'-A m with activity decreased by only fivefold to sixfold compared with its preferred capped substrate. We finally discuss the relationship between PCIF1-catalyzed RNA methylation, shown here to have broader substrate specificity than previously appreciated, and that of the RNA demethylase fat mass and obesity-associated protein (FTO), which demonstrates PCIF1-opposing activities on capped RNAs., Competing Interests: Conflict of interest N. D., E. J. W. and I. R. C. are employees of New England Biolabs, Inc, which is a manufacturer and vendor of molecular biology reagents, including several enzymes and buffers used in this study. This affiliation does not affect the authors’ impartiality, adherence to journal standards and policies, or availability of data. The other authors (D. Y., J. Z., T. W., R. M. B., X. Z., and X. C.) declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Edwardsiella tarda can cause fatal gastro-/extraintestinal diseases in fish and humans. Overuse of antibiotics has led to antibiotic resistance and contamination in the environment, which highlights the need to find new antimicrobial agents. In this study, the marine peptide-N6 was amidated at its C-terminus to generate N6NH2. The antibacterial activity of N6 and N6NH2 against E. tarda was evaluated in vitro and in vivo; their stability, toxicity and mode of action were also determined. Minimal inhibitory concentrations (MICs) of N6 and N6NH2 against E. tarda were 1.29–3.2 μM. Both N6 and N6NH2 killed bacteria by destroying the cell membrane of E. tarda and binding to lipopolysaccharide (LPS) and genomic DNA. In contrast with N6, N6NH2 improved the stability toward trypsin, reduced hemolysis (by 0.19% at a concentration of 256 μg/mL) and enhanced the ability to penetrate the bacterial outer and inner membrane. In the model of fish peritonitis caused by E. tarda, superior to norfloxacin, N6NH2 improved the survival rate of fish, reduced the bacterial load on the organs, alleviated the organ injury and regulated the immunity of the liver and kidney. These data suggest that the marine peptide N6NH2 may be a candidate for novel antimicrobial agents against E. tarda infections. [ABSTRACT FROM AUTHOR]

Scope: Brown and brite adipocytes within the mammalian adipose organ provide non-shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3-series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial., Methods and Results: Mice are housed in a thermoneutral environment eliminating the superimposing effect of mild cold-exposure on thermogenic adipocyte recruitment. Dietary fish oil supplementation in two different inbred mouse strains neither affects body mass trajectory nor enhances the recruitment of brown and brite adipocytes, both in the presence and absence of a β3-adrenoreceptor agonist imitating the effect of cold-exposure on adipocytes. In line with these findings, dietary fish oil supplementation of persons with overweight or obesity fails to recruit thermogenic adipocytes in subcutaneous adipose tissue., Conclusion: Thus, the authors' data question the hypothesized potential of n3-PUFA as modulators of adipocyte-based thermogenesis and energy balance regulation., (© 2020 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)