Ad Types Research Articles

Gene therapy in Aβ-induced cell and mouse models of Alzheimer’s disease through compensating defective mitochondrial complex I function

BackgroundAlzheimer’s disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models.MethodsThe differentiated human neural cells were induced by Aβ1–42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aβ1–42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect.ResultsThe expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect.ConclusionsCompensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aβ-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.

Interactive vs transactional: how social media ads engage consumers with disparate regulatory orientation and lay rationalism

PurposeThe growing number of firms leveraging social media ads highlight the urgent need for firms to understand social media ads and their effects on consumer perceptions and attitudes. This research examines whether and how different types of social media ads exert influences on ad engagement and how consumers’ psychological characteristics including regulatory orientation and lay rationalism moderate the influence of social media ads on ad engagement.Design/methodology/approachThis research conducts three quasi experiments featuring two types of social media ads – interactive and transactional – to collect empirical evidence. Results are analyzed using ANOVA and Process in SPSS.FindingsThis research reveals that interactive ads lead to higher perceived enjoyment and perceived responsiveness, which further lead to higher ad engagement. Promotion focus moderates the effect of social media ads (interactive vs transactional ads) on perceived enjoyment and perceived responsiveness, and lay rationalism moderates the effect on perceived responsiveness, while prevention focus has no such effect.Originality/valueFirst, this research establishes the connection between ad types and ad engagement in social media, which offers a new perspective to understand ad engagement. Second, it explores the underlying mechanisms of processing different types of social media ads. Third, it justifies the moderating effects of consumers’ regulatory orientation and lay rationalism on the effects of ad types on ad engagement, providing the first evidence on the moderating role of consumers’ lay rationalism in ad processing. This research helps firm marketers to fine-tune their social media ads according to consumer characteristics.

Association between ABO genotypes and risk of dementia and neuroimaging markers: roles of sex and APOE status.

Whether the relationships between ABO blood genotypes (AA, AO, BB, BO, AB, and OO) and dementia are modified by gender and APOE status has been unclear. We used data from the UK Biobank, a population-based cohort study of 487,425 individuals. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) between ABO genotypes and risk of dementia. Multivariable linear regression models were used to estimate the relationship between ABO genotypes and MRI-based brain indices. Overall, 487,425 participants were included at baseline. After 34 million person-years follow up, 7,548 patients developed all-cause dementia. Before stratifying by sex and APOE status, compared to OO genotype, BB genotype was associated with increased risk of all-cause dementia (1.36, 1.03-1.80) and other types dementia (1.65, 1.20-2.28). After stratifying by sex, only in males, BB genotype was associated with higher risk of all-cause dementia (1.44, 1.02-2.09) and other types of dementia (1.95, 1.30-2.93). AB genotype in males was also associated with increased AD (1.34, 1.04-1.72). After further stratifying by APOE e4 status, BB genotype with two APOE e4 alleles showed even stronger association with all-cause dementia 4.29 (1.57, 11.72) and other types dementia (5.49, 1.70-17.69) in males. Also in males, AA genotype with one APOE e4 was associated with increased risks of all-cause dementia (1.27, 1.04-1.55), AD (1.45, 1.09-1.94) and other types dementia (1.40, 1.08-1.81). Linear regression models showed that in both sexes with APOE e4, AA genotype was associated with reduced total grey matter volume. Sex and APOE e4 carrier status modified the association between ABO genotypes and risk of dementia. In males, BB genotype was consistently associated with increased risk of dementia, especially in those with two APOE e4 alleles. Also, in males with one APOE e4, AA genotype might be linked to higher risk of dementia.

Comprehensive genomic profiling of advanced anal adenocarcinoma.

4 Background: Anal adenocarcinoma (anal AD) is a rare and aggressive gastrointestinal malignancy. Because of its rarity, no standard therapy is established and treatment strategy for advanced rectal adenocarcinoma (rectal AD) is extrapolated. Little is known for genetic alterations (GAs) and their therapeutic implications in advanced anal AD. We aim to investigate to clarify genomic profiles of advanced anal AD in comparison of advanced rectal AD. Methods: We retrospectively extracted data on patients with advanced anal AD and advanced rectal AD who underwent comprehensive genomic profiling (CGP) tests and were registered for the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan. CGP tests were performed by NCC Oncopanel or FoundationOne CDx. We examined somatic GAs, microsatellite instability (MSI) status, and tumor mutation burden (TMB). TMB-high was defined as ≥10 mutations/Mb. Actionable GAs were counted if they were classified as “pathogenic/oncogenic” or “likely pathogenic/likely oncogenic” variants. Druggable GAs are actionable GAs with approved drugs for anal AD or other types of cancer or clinical trials showing efficacy for either anal AD or different types of cancer. Results: From June 2019 to April 2023, 45 patients with anal AD and 1915 patients with rectal AD were enrolled into the C-CAT database. In the anal AD group, most common actionable GAs were TP53 (89%), KRAS (51%), ERBB3 (22%), MYC (20%), SMAD4 (20%), and ERBB2 (11%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of actionable GAs in ERBB3 (22% vs. 2%, p < 0.01), MYC (20% vs. 8%, p < 0.01), and BRCA2 (7% vs. 1%, p < 0.01), and a significantly lower frequency of actionable GAs in APC (7% vs. 85%, p < 0.01). The proportion of MSI-high and TMB-high in the anal AD group and the rectal AD group were 0% vs. 0.2% (p = 0.79), and 7% vs. 5% (p = 0.54). Common druggable GAs in anal ADs included KRAS G12D mutation (22%), ERBB2 amplification (7%), BRCA2 mutation (7%), BRAF V600E mutation (2%). Compared with the rectal AD group, the anal AD group had a significantly higher frequency of druggable GAs in BRCA2 mutation (7% vs. 1%, p < 0.01). Conclusions: The present study showed that anal AD had a different profile of GAs compared with advanced rectal AD. CGP tests are useful tool for identifying druggable GAs in advanced anal AD for expanding therapeutic opportunities.

85 Performance Consistency on a Measure of Sustained and Selective Attention

Objective:Attention concerns, particularly difficulties with focusing and regulating attention, are reported in diverse clinical contexts. The Ruff 2&7 Selective Attention Test (Ruff 2&7; Ruff & Allen, 1996) is a measure of sustained and selective attention that assesses automatic detection and effortful processing. The goal of this study was to create an internal consistency metric within this test and to determine cognitive predictors by evaluating associations with executive control of attention and other cognitive skills. It was hypothesized that those who are more consistent across Ruff 2&7 performance would have more robust executive functioning skills, particularly those related to regulating and directing attention and the planning and utilization of cognitive resources.Participants and Methods:The current study examined a clinical sample of 98 United States veterans with a history of mild traumatic brain injury. After excluding invalid cases (n=24), the final sample consisted of 74 veterans (Age=38.5 (8.9) years old; 13.9 (2.2) years of education; 78% male; 82% white, 7% Black, 8% Hispanic, 2% Asian). A consistency score was defined as the absolute value of the intertrial change in target hits plus errors across each pair of trials of the same stimulus type (Automatic Detection, AD, and Controlled Search, CS). Hierarchical linear regression modeling was used to evaluate the relative contributions of memory and executive functions (Rey Auditory Verbal Learning Test, Delis-Kaplan Executive Function System Tower Test, phonemic fluency, Trail Making Test B) and subjective symptom report (PTSD Checklist for DSM-5, Barkley Adult ADHD Rating Scale for DSM-IV).Results:The mean deviation scores for the two trial types were similar (AD mean=13.6, SD=5.9; CS mean=13.6, SD=5.3). In predicting consistency across AD trials, delayed recall contributed 11% unique variance (p=.013), while no other block was statistically significant. For CS trials, self-reported PTSD and inattention symptoms contributed a combined 20% of unique variance to the model (p=.007), while there were no statistically significant cognitive predictors in this model.Conclusions:Contrary to expectation, executive function measures did not explain statistically significant variance in performance across either trial type. Less consistent performance on AD trials was associated with weaker verbal memory. Less consistent performance on CS trials, which theoretically require greater executive control, was not associated with any cognitive scores, but was associated with more severe self-reported psychological and inattention symptoms. These findings buttress the conceptual distinction between AD and CS trial types, and they point to both cognitive and non-cognitive underpinnings of performance consistency.

Development of oncolytic and gene therapy vectors based on adenovirus serotype 4 as an alternative to adenovirus serotype 5.

Adenoviral vectors are among the most frequently used vectors for gene therapy and cancer treatment. Most vectors are derived from human adenovirus (Ad) serotype 5 despite limited applicability caused by pre-existing immunity and unfavorable liver tropism, whereas the other more than 100 known human serotypes remain largely unused. Here, we screened a library of human Ad types and identified Ad4 as a promising candidate vector. Reporter-gene-expressing viruses representative of the natural human Ad diversity were used to transduce an array of muscle cell lines and two- or three-dimensional tumor cultures. The time-course of transgene expression was monitored by fluorescence or luminescence measurements. To generate replication-deficient Ad4 vector genomes, successive homologous recombination was applied. Ad4, 17 and 50 transduced human cardiomyocytes more efficiently than Ad5, whereas Ad37 was found to be superior in rhabdomyocytes. Despite its moderate transduction efficiency, Ad4 showed efficient and long-lasting gene expression in papillomavirus (HPV) positive tumor organoids. Therefore, we aimed to harness the potential of Ad4 for improved muscle transduction or oncolytic virotherapy of HPV-positive tumors. We deleted the E1 and E3 transcription units to produce first generation Ad vectors for gene therapy. The E1- and E1/E3-deleted vectors were replication-competent in HEK293 cells stably expressing E1 but not in the other cell lines tested. Furthermore, we show that the Ad5 E1 transcription unit can complement the replication of E1-deleted Ad4 vectors. Our Ad4-based gene therapy vector platform contributes to the development of improved Ad vectors based on non-canonical serotypes for a broad range of applications.

Study on Ad Effectiveness by Ad and Product Types on Shopping Platforms: Focusing on China’s Pinduoduo

Study on Ad Effectiveness by Ad and Product Types on Shopping Platforms: Focusing on China’s Pinduoduo

단어 형성의 관점에서 본 전문 용어 줄임말의 유형과 특성

This paper aims at revealing the types and properties of term abbreviations in Urimalsaem. Until now, abbreviations have been discussed only in the basic types such as AC, AD, BC, and BD. However, even when targeting term abbreviations for Urimalsaem, the types are not so simple. In this respect, in order to categorize 794 term abbreviations of Urimalsaem, in addition to the ‘basic type’, ‘extended type’ and ‘applied type’ were assumed. In addition, the ‘complex type’ which is combined with the basic type and the extended type was considered as a separate type, and those that did not belong to any type were grouped into ‘other type’. Through this classification, except for ‘other type’, they were subdivided into 11 extended types, 14 applied types, and 1 complex types in addition to 4 basic types. This results clearly show that the term abbreviation types are very complicated themselves. These abbreviation types have a very high sum of the proportions of the extended, applied, and complex types, although the proportion of the overall basic types is over half at 53.4%. In the case of the AD type, the ratio of the extended type (15.74%) is more than twice as high as that of the basic type (16.30%). On the other hand, compared to the ratio of AC and AD types, BC and BD types are not very productive in abbreviation methods because the sum is only 5.66% of them. When it comes to the abbreviation type, it can also be seen that the number of syllables plays a very important role in the formation of abbreviations. On the other hand, as the structural characteristics of the abbreviation, AC and AD types with the highest type frequency and item frequency were mentioned. The relationship between acronyms for AC type and blended words for AD type was also noted. In addition, among the term abbreviations, some elements appear repeatedly and continuously as former or latter position. Some of them are affixes, but others are not. Therefore, they can be separately called ‘abbreviators’. It is worth noting that these abbreviators make us predict the type of term abbreviations not just in current but also in future.

사진 기반 vs. 동영상 기반 SNS 광고 유형이 광고 수용자의 공감 및 공유의도에 미치는 영향: 사진 및 동영상內 동적수준의 조절효과를 중심으로

사진 기반 vs. 동영상 기반 SNS 광고 유형이 광고 수용자의 공감 및 공유의도에 미치는 영향: 사진 및 동영상內 동적수준의 조절효과를 중심으로

Influence of Heparan Sulfate Proteoglycans and Factor X on species D Human Adenovirus Uptake and Transduction.

More than 100 human adenovirus (Ad) types were identified, of which species D comprises the largest group. Heparan sulfate proteoglycans (HSPGs) were shown to function as cell surface receptors for cell binding and uptake of some Ads, but a systematic analysis of species D Ads is lacking. Previous research focused on Ad5 and blood coagulation factor X (FX) complexes, which revealed that Ad5 can transduce cells with low expression levels of its main coxsackievirus-adenovirus receptor in the presence of high HSPG expression levels in a FX dependent manner. Based on our reporter gene-tagged Ad-library, we explored for the first time a broad spectrum of species D Ads to study the role of HSPG on their cellular uptake. This study was performed on three Chinese Hamster Ovary (CHO) cell lines with different forms of HSPG (only proteoglycan (745), non-sulfated HSPG (606) or sulfated HSPG (K1)). The effect of Ad:FX complexes on Ad uptake was explored in the presence of physiological levels of FX in blood (6-10 µg/mL). We found that sulfation of HSPG plays an important role in cellular uptake and transduction of FX-bound Ad5 but neither HSPG nor FX influenced uptake of all tested species D Ads. Because FX has no influence on transduction efficiencies of species D Ads and therefore may not bind to them, these Ads may not be protected from attack by neutralizing IgM antibodies or the complement pathway, which may have implications for species D Ads used as vaccine and gene therapy vectors.

Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo

The majority of adenovirus (Ad) vectors are based on human Ad type 5, which is a member of Ad species C. Species C also includes the closely-related types 1, 2, 6, 57 and 89. It is known that coagulation factors bind to Ad5 hexon and play a key role in the liver tropism of Ad5 vectors, but it is unclear how coagulation factors affect vectors derived from other species C Ads. We evaluated species C Ad vectors both in vitro and following intravenous injection in mice. To assess the impact of hexon differences, we constructed chimeric Ad5 vectors that contain the hexon hypervariable regions from other species C types, including vectors with hexon mutations that decreased coagulation factor binding. After intravenous injection into mice, vectors with Ad5 or Ad6 hexon had strong liver tropism, while vectors with chimeric hexon from other Ad types had weaker liver tropism due to inhibition by natural antibodies and complement. In addition, we discovered a novel ability of hexon to bind prothrombin, which is the most abundant coagulation factor in blood, and we found striking differences in the affinity of Ads for human, mouse and bovine coagulation factors. When compared to Ad5, vectors with non-Ad5 species C hexons had considerably higher affinity for both human and mouse prothrombin. Most of the vectors tested were strongly dependent on coagulation factors for liver transduction, but vectors with chimeric Ad6 hexon showed much less dependence on coagulation factors than other vectors. We found that in vitro neutralization experiments with mouse serum predicted in vivo behavior of Ad5 vectors, but in vitro experiments did not predict the in vivo behavior of vectors based on other Ad types. In sum, hexons from different human Ad species C viruses confer diverse properties on vectors, including differing abilities to target the liver.

The bidirectional relationship between anxiety disorders and alcohol use disorders in adults: Findings from a longitudinal population-based study

BackgroundAnxiety disorders (AD) and alcohol use disorder (AUD) frequently co-occur, but the temporal order of the association is unclear. We have determined the association between AD and the presence and first-onset of AUD, and vice versa. MethodsData were used from n = 6.646 participants and four measurement waves (baseline, 3-, 6- and 9-years) of the Netherlands Mental Health Survey and Incidence Study 2 (NEMESIS-2), a cohort study of the Dutch general population aged 18–64 years. AD and AUD were assessed with the Composite International Diagnostic Interview 3.0. Multilevel logistic autoregressive models were controlled for previous-wave AD or AUD, sociodemographics (Model 1), smoking and clinical factors (Model 2). ResultsPeople with AUD had a higher risk of present (OR = 1.65, 95 % CI 1.11–2.43; Model 2) and first-onset (OR = 2.03, 95 % CI 1.17–3.51; Model 2) AD in 3-years follow-up intervals than people without AUD. Vice versa, people with AD also had a higher sociodemographics-adjusted risk of present and first-onset AUD over 3-years follow-up intervals, but these associations attenuated into insignificance after adjustment for smoking and clinical variables.LimitationsFor statistical power reasons we were not able to analyze 9-year follow-up data or distinguish between AD and AUD types. ConclusionsOur results indicate a bidirectional relationship between AD and AUD; especially those with severe AD (medication use, comorbid depression) are at risk of developing AUD. Health care professionals should focus on prevention of AD in AUD patients and prevention of AUD in patients with (more severe) AD. Further research should investigate the mechanisms underlying the observed associations.

Novel Group C Oncolytic Adenoviruses Carrying a miRNA Inhibitor Demonstrate Enhanced Oncolytic Activity In Vitro and In Vivo.

Oncolytic adenoviruses (OAd) represent an attractive treatment option for cancer. Clinical efficacy of commonly utilized human adenovirus type 5 (Ad5)-based oncolytic viruses is limited by variable expression levels of the coxsackie- and adenovirus receptor (CAR) in tumor cells and high prevalence of neutralizing antibodies against human Ad5. However, previous studies have highlighted alternative human Ad types as promising candidates for oncolytic therapy. In this study, we generated novel OAds based on Ad1, -2, -5, and -6 derived from species C Ads. These OAds contain a 24-bp deletion in the early gene E1A for tumor selective replication and express the RNAi inhibitor P19. We examined these OAds for in vitro anticancer activity on various cancer cell lines derived from lung, colon, gynecologic, bone, and pancreatic carcinoma. In most surveyed cell lines, OAds based on Ad1, -2, and -6 demonstrated higher cell lysis capability compared with Ad5, suggesting enhanced oncolytic potential. Moreover, enhanced oncolytic activity was associated with P19 expression in a cell type-dependent manner. We further explored a A549 tumor xenograft mouse model to compare the novel OAds directly with Ad5 and H101, an oncolytic adenovirus used in clinical trials. These P19-containing OAds based on Ad1, -2, and -6 showed significantly decelerated tumor progression compared with H101, indicating better antitumor potency in vivo. Our studies provide a novel path for OAd development based on alternative Ad types with improved effectiveness by RNA interference suppression.

Nonhuman Adenoviral Vector-Based Platforms and Their Utility in Designing Next Generation of Vaccines for Infectious Diseases.

Several human adenoviral (Ad) vectors have been developed for vaccine delivery owing to their numerous advantages, including the feasibility of different vector designs, the robustness of elicited immune responses, safety, and scalability. To expand the repertoire of Ad vectors for receptor usage and circumvention of Ad vector immunity, the use of less prevalent human Ad types or nonhuman Ads were explored for vector design. Notably, many nonhuman Ad vectors have shown great promise in preclinical and clinical studies as vectors for vaccine delivery. This review describes the key features of several nonhuman Ad vector platforms and their implications in developing effective vaccines against infectious diseases.

Human Species D Adenoviruses Isolated from Diarrheal Feces Show Low Infection Rates in Primary Nasal Epithelial Cells.

The importance of adenovirus (Ad) research is significantly increasing with respect to virotherapy for vaccine development, tumor, and gene therapy. Due to the different species and subtypes of this virus, the characterization of the biological significance of especially rare Ad is necessary. Previously, rare Ad types 70, 73, and 74 were originally isolated from fecal samples of immunocompromised patients and they represent recombinants of other Ad types. Here we investigated transduction experiments of these reporter gene tagged Ad types in primary cells exemplified by subject-derived primary nasal epithelial cells (NAEPCs). To analyze the transduction rates, we performed flow cytometry, quantitative polymerase chain reaction (PCR), and cytokine analyses 25 h post-infection. We found that, in contrast to Ad type 5 (as a positive control), the transduction rates of NAEPCs with Ad types 70, 73, and 74 were interestingly low. The major Ad receptor (coxsackievirus-adenovirus receptor and CD46) expression levels showed no significant change after infection with Ad types 70, 73 and 74. Moreover, Interleukin 6 (IL-6) was not released after in vitro Ad transduction. Due to the high risk of developing life-threatening complications in immunocompromised patients by these human species D Ads, even more attention needs to be investigated into the development of diagnostic and therapeutic concepts to prevent and treat those opportunistic infections in susceptible patients.

Imaging beta-amyloid (A\u03b2) burden in the brains of middle-aged individuals with alcohol-use disorders: a [11C]PIB PET study

No in vivo human studies have examined the prevalence of Alzheimer’s disease (AD) neuropathology in individuals with alcohol-use disorder (AUD), although recent research suggests that a relationship between the two exists. Therefore, this study used Pittsburgh Compound-B ([11C]PiB) PET imaging to test the hypothesis that AUD is associated with greater brain amyloid (Aβ) burden in middle-aged adults compared to healthy controls. Twenty healthy participants (14M and 6F) and 19 individuals with AUD (15M and 4F), all aged 40–65 years, underwent clinical assessment, MRI, neurocognitive testing, and positron emission tomography (PET) imaging. Global [11C]PiB standard uptake value ratios (SUVRs), cortical thickness, gray matter volumes (GMVs), and neurocognitive function in subjects with AUD were compared to healthy controls. These measures were selected because they are considered markers of risk for future AD and other types of neurocognitive dysfunction. The results of this study showed no significant differences in % global Aβ positivity or subthreshold Aβ loads between AUD and controls. However, relative to controls, we observed a significant 6.1% lower cortical thickness in both AD-signature regions and in regions not typically associated with AD, lower GMV in the hippocampus, and lower performance on tests of attention as well as immediate and delayed memory in individuals with AUD. This suggest that Aβ accumulation is not greater in middle-aged individuals with AUD. However, other markers of neurodegeneration, such as impaired memory, cortical thinning, and reduced hippocampal GMV, are present. Further studies are needed to elucidate the patterns and temporal staging of AUD-related pathophysiology and cognitive impairment. Imaging β-amyloid in middle age alcoholics as a mechanism that increases their risk for Alzheimer’s disease; Registration Number: NCT03746366.

Species D Adenoviruses as Oncolytic Viral Vectors.

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.

Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy.

Oncolytic adenoviruses (Ads) are promising tools for cancer therapeutics. However, most Ad-based therapies utilize Ad type 5 (Ad5), which displays unsatisfying efficiency in clinical trials, partly due to the low expression levels of its primary coxsackievirus and adenovirus receptor (CAR) on tumor cells. Since the efficacy of virotherapy strongly relies on efficient transduction of targeted tumor cells, initial screening of a broad range of viral agents to identify the most effective vehicles is essential. Using a novel Ad library consisting of numerous human Ads representing known Ad species, we evaluated the transduction efficiencies in four breast cancer (BC) cell lines. For each cell line over 20 Ad types were screened in a high-throughput manner based on reporter assays. Ad types featuring high transduction efficiencies were further investigated with respect to the percentage of transgene-positive cells and efficiencies of cellular entry in individual cell lines. Additionally, oncolytic assay was performed to test tumor cell lysis efficacy of selected Ad types. We found that all analyzed BC cell lines show low expression levels of CAR, while alternative receptors such as CD46, DSG-2, and integrins were also detected. We identified Ad3, Ad35, Ad37, and Ad52 as potential candidates for BC virotherapy.

사고경향과 종교, 광고형태가 영화광고에 미치는 영향

본 연구는 종교가 광고에 미치는 영향을 관련변인들과의 상호작용을 통해 알아보았다. 구체적으로 사고경향(종합적 사고경향 vs 분석적 사고경향)×종교(기독교 신자 vs 불교 신자)×광고형태(노스탤지어 광고 vs 일반 광고)의 2×2×2의 실험참여자 간 설계(between-subject design)로 구성하여 가설에 따라 종속변인인 광고태도, 영화태도에 대한 상호작용효과 분석을 실시하였다. 그 결과, 사고경향의 주효과가 나타났다. 사고경향은 종속변인인 광고태도, 영화태도에 대해서 모두 종합적 사고경향 집단이 분석적 사고경향집단 보다 더 긍정적인 것으로 나타났다. 광고형태 또한 주효과가 나타났다. 광고형태는 일반 광고에 비해 노스탤지어 광고의 광고태도와 영화태도가 더 긍정적인 것으로 나타났다. 그리고 종교, 광고형태, 사고경향이 광고태도에 대해서 3원 상호작용을 나타냈다. 크리스챤의 경우 종합적 사고경향 집단보다 분석적 사고경향 집단에서 광고형태에 따른 광고태도의 차이가 더 크게 나타났다. 이와는 대조적으로 불교 신자의 경우 분석적 사고경향 집단보다 종합적 사고경향 집단에서 광고형태에 따른 광고태도의 차이가 더 크게 나타났다. 광고태도에 대한 3원 상호작용이 나타난 것은, 종교별로 광고형태에 대하여 사고경향이 다르게 작용하며 태도에 영향을 미치는 것으로 이해할 수 있다. 본 연구는 수많은 인구가 관련된 종교가 때로는 커뮤니케이션의 고려 대상이 될 수 있다는 실무적 시사점을 함의한다.

Characteristic of slow growth in cell culture of adenovirus type 54 causing nationwide outbreak epidemic keratoconjunctivitis in Japan

To characterize the virological features of adenovirus type 54 (Ad54) causing nationwide outbreak of severe epidemic keratoconjunctivitis (EKC) in Japan, we comparatively analysed the viral propagation phenotype of Ad54 and other Ads: type 37 (Ad37), 64 (Ad64), and 5 (Ad5), in A549 cells quantitatively. Laboratory investigation. We compared the growth rate of Ads using copy numbers and cytopathic effect observation during propagation in A549 cell lines. Expressions of mRNA of E1 gene were also calculated and compared. Phylogenetic analysis of the region, including putative promoter of E1 gene and E1 open reading frame (ORF), were performed. Increases in viral loads, growth rate, and viral propagation were slower for Ad54 than for other Ads. The expression level of the E1 gene per infected cell was lower for Ad54 than for other Ad types on post-infection day 1. Phylogenetic analysis of the E1 gene putative promoter and ORF revealed Ad54 was the closest to Ad type 8. The propagation of Ad54 in A549 is slow compared with Ad37, Ad64 and Ad5. This slow propagation could have been caused by slow genomic replication resulting from delayed viral entry or E1 transcription initiation. The EKC caused by Ad54 needs more attention because the slow propagation of Ad54 may contribute to prolonged disease duration.