Miracle-dz/UniFAR-FTUs huggingface dataset:
Androgen pathway stimulates MicroRNA‐216a transcription to suppress the tumor suppressor in lung cancer‐1 gene in early hepatocarcinogenesis

Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated. By examining the expression of 22 HCC‐related miRNAs between precancerous and cancerous liver tissues, we found miR‐216a and miR‐224 were significantly up‐regulated, starting from the precancerous stage. Furthermore, the elevation of miR‐216a was mainly identified in male patients. To study this gender difference, we demonstrated that pri‐miR‐216a is activated transcriptionally by the androgen pathway in a ligand‐dependent manner and is further enhanced by the hepatitis B virus X protein. The transcription initiation site for pri‐miR‐216a was delineated, and one putative androgen‐responsive element site was identified within its promoter region. Mutation of this site abolished the elevation of pri‐miR‐216a by the androgen pathway. One target of miR‐216a was shown to be the tumor suppressor in lung cancer‐1 gene (TSLC1) messenger RNA (mRNA) through the three target sites at its 3′ untranslated region. Finally, the androgen receptor level increased in male liver tissues during hepatocarcinogenesis, starting from the precancerous stage, with a concomitant elevation of miR‐216a but a decrease of TSLC1. Conclusion: The current study discovered the up‐regulation of miRNA‐216a by the androgen pathway and a subsequent suppression of TSLC1 as a new mechanism for the androgen pathway in early hepatocarcinogenesis. (HEPATOLOGY 2012)
Expression analysis of the nucleocytoplasmic lectin ‘Orysata’ from rice in Pichia pastoris

The Oryza sativa lectin, abbreviated Orysata, is a mannose‐specific, jacalin‐related lectin expressed in rice plants after exposure to certain stress conditions. Expression of a fusion construct containing the rice lectin sequence linked to enhanced green fluorescent protein in Bright Yellow 2 tobacco cells revealed that Orysata is located in the nucleus and the cytoplasm of the plant cell, indicating that it belongs to the class of nucleocytoplasmic jacalin‐related lectins. Since the expression level of Orysata in rice tissues is very low the lectin was expressed in the methylotrophic yeast Pichia pastoris with the Saccharomycesα‐factor sequence to direct the recombinant protein into the secretory pathway and express the protein into the medium. Approximately 12 mg of recombinant lectin was purified per liter medium. SDS/PAGE and western blot analysis showed that the recombinant lectin exists in two molecular forms. Far western blot analysis revealed that the 23 kDa lectin polypeptide contains an N‐glycan which is absent in the 18.5 kDa polypeptide. Characterization of the glycans present in the recombinant Orysata revealed high‐mannose structures, Man9–11 glycans being the most abundant. Glycan array analysis showed that Orysata interacts with high‐mannose as well as with more complex N‐glycan structures. Orysata has potent anti‐human immunodeficiency virus and anti‐respiratory syncytial virus activity in cell culture compared with other jacalin‐related lectins.
The Impact of New Legislation on Child Restraint System (CRS) Misuse and Inappropriate Use in Australia

Objective: The current study aimed to investigate the incidence of child restraint system (CRS) misuse and/or inappropriate use of CRS through an Australian CRS inspection program conducted by CRS fitting specialists between October 2004 and October 2011 and to determine whether CRS misuse and/or inappropriate use of CRS changed following new Australian legislation regarding CRS and motor vehicle restraint use for children aged 7 years and under. Methods: Participants were recruited through an advertisement for free CRS inspections displayed at childcare centers, kindergartens, community centers, hospitals, and child expos. At each inspection, a CRS fitting specialist inspected each child in their CRS while in their vehicle and reported to the owner of the CRS on the installation of the child restraint(s) and/or system(s) and any fitting faults and/or concerns with the fitting and/or use of the child restraint(s) and or system(s). Results: Results are based on the inspection of 2674 CRS. Of all of the CRS inspected, the majority (79%) were reported as having at least one instance of misuse and/or inappropriate use. The most common forms of CRS misuse and/or inappropriate use observed were harness strap errors (twisted, poorly adjusted, and/or incorrectly positioned, 41%), seat belt errors (incorrectly routed, twisted, and/or incorrectly adjusted, 32%), and a missing or incorrect fitting of the gated buckle/locking clip (24%). Significant differences were found across the proportion of CRS misuse and/or inappropriate use across restraint types (infant restraint/forward-facing CRS/convertible [birth to 18 kg] CRS/convertible [8–26 kg] CRS/boosters [booster seat/cushion/booster with harness combination]), χ2(4) = 147.852, P < . 001. CRS misuse and/or inappropriate use were most prevalent among convertible CRS (birth to 18 kg; 87%), forward-facing CRS (85%), and convertible CRS (8–26 kg; 81%), compared to infant restraints (73%) and booster seats (booster seats/cushions/boosters with H-harness combination; 65%). There was no significant difference in the proportion of CRS with misuse and/or inappropriate use across the pre- and post-legislation period (80% vs. 77%), χ2(1) = 1.545, P > . 5. Conclusions: Based on the findings of the current study, it was concluded that, despite the introduction of new, definitive CRS legislation, CRS misuse and/or inappropriate use remains widespread in Australia. The findings highlight the need for CRS education and legislation that include information on correct CRS use, as well as information on appropriate CRS use, in order to provide specialized protection for child vehicle occupants in the event of a motor vehicle crash.
The lipid translocase, ABCA4: seeing is believing

Mutations to members of the A subfamily of ATP binding cassette (ABC) proteins are responsible for a number of diseases; typically they are associated with aberrant cellular lipid transport processes. Mutations to the ABCA4 protein are linked to a number of visual disorders including Stargardt’s disease and retinitis pigmentosa. Over 500 disease‐associated mutations in ABCA4 have been demonstrated; however, the genotype–phenotype link has not been firmly established. This shortfall is primarily because the function of ABCA4 in the visual cycle is not yet fully understood. One hypothesis suggests that ABCA4 mediates the trans‐bilayer translocation of retinal‐phosphatidylethanolamine conjugates to facilitate the retinal regeneration process in the visual cycle. This review examines the evidence to support, or refute, this working hypothesis on the function of this clinically important protein.
Response of broilers to 3 weeks feed restriction initiated at different time periods

One hundred and forty four Anak broilers were subjected to either ad libitum feeding or 50% ad libitum feeding for a period of 3 weeks starting from 2nd, 3rd, 4th, 5th or 6th week of age and then returned to ad libitum feeding to market age. Feed intake was significantly reduced (P<0.05). Initiation of broilers to 50% of ad libitum feeding at the 2nd week of age produced a significantly higher weight gain and better feed to gain ratio compared with the control (P<0.05). Initiation of broilers to 50% ad libitum feeding beyond the 3rd week resulted in poorer performance of broilers compared with the control (P<0.05). Feed restriction as applied in this study did not have any significant effects on broilers initiated at the 2nd or 3rd week and the control. However, retention of these nutrients were significantly reduced (P<0.05) in birds initiated into feed restriction beyond the 3rd week. The economic data showed that 50% of ad libitum feeding initiated at the 2nd Week of age resulted in significant reduction in the cost of production and cost to benefit ratio (P<0.05). The benefit in terms of Naira and kobo was also significantly increased (P<0.05). It was then concluded that, initiating broilers to 50% of ad libitum feeding for 3 weeks starting at the 2nd week of age offered a better economic gain than the usual ad libitum feeding.
The Effect of Earlier or Automatic Collision Notification on Traffic Mortality by Survival Analysis

Objective: This article explores the effects of earlier emergency medical services (EMS) or automatic collision notification (ACN) and EMS arrival on passenger/driver survivability within the short time frame following traffic crashes. Methods: Survival analysis techniques are used extensively in this study, because traffic crash and EMS data are closely associated with time. The Kaplan-Meier estimator and life curves are applied to compare the survival rates between 2 or more conditions (e.g., earlier verus late EMS notification); The Weibull model with 3 parameters is used to predict mortality over time; furthermore, the Cox proportional hazard model explores multiple risk factors related to traffic mortality. Results: Based on Fatality Analysis Reporting System (FARS) data from 2005 to 2009, Kaplan-Meier life curves clearly showed the benefits associated with earlier notifications (approximately 1.84% fatality reduction within a time frame of 6 h after a crash) and earlier arrivals, and the Weibull model with 3 parameters reasonably predicted the fatality trends. The relative risks (RRs) associated with collision notification, arrival, location, and age were obtained from a multiple Cox regression model, and the relatively higher fatality hazard (2.4% higher) associated with the later notification of more than 1 min was studied in detail. Conclusions: This article obtains the driver/passenger survival probabity differences over time under different conditions of collision notifications, EMS arrivals, and crash locations; furthermore, this analysis provides an estimation of the lives that could potentially be saved (approximately 154 to 290 per year) due to earlier ACN.
The N‐terminal region of the bacterial DNA polymerase PolC features a pair of domains, both distantly related to domain V of the DNA polymerase III τ subunit

PolC is one of two essential replicative DNA polymerases in Bacillus subtilis and other Gram‐positive bacteria. The 3D structure of PolC has recently been solved, yet it lacks the N‐terminal region. For this PolC region of ∼ 230 residues, both the structure and function are unknown. In the present study, using sensitive homology detection and comparative protein structure modeling, we identified, in this enigmatic region, two consecutive globular domains, PolC‐NI and PolC‐NII, which are followed by an apparently unstructured linker. Unexpectedly, we found that both domains are related to domain V of the τ subunit, which is part of the bacterial DNA polymerase III holoenzyme. Despite their common homology to τ, PolC‐NI and PolC‐NII exhibit very little sequence similarity to each other. This observation argues against simple tandem duplication within PolC as the origin of the two‐domain structure. Using the derived structural models, we analyzed residue conservation and the surface properties of both PolC N‐terminal domains. We detected a surface patch of positive electrostatic potential in PolC‐NI and a hydrophobic surface patch in PolC‐NII, suggesting their possible involvement in nucleic acid and protein binding, respectively. PolC is known to interact with the τ subunit, however, the region responsible for this interaction is unknown. We propose that the PolC N‐terminus is involved in mediating the PolC‐τ interaction and possibly also in binding DNA.
Characteristics of 1226 Alcohol-Positive Drivers Involved in Nonfatal Traffic Crashes in Shanghai, China

Objective: The purpose of our study was to better characterize and evaluate drunk driving for governmental reference in order to further reduce alcohol-impaired driving. Method: This article reports the characteristics of 1226 alcohol-positive drivers with blood alcohol concentrations (BACs) at or over the legal limit of 0.20 mg/mL involved in nonfatal traffic accidents in Shanghai, China, from 2008 to 2011. The mean BAC, age, and gender of these drivers are discussed as well as the vehicle types and times of day when the crashes occurred. Results: The mean BAC was 1.41 mg/mL and the mean age was 38 years old, and the vast majority of drivers were male (96.9%). The mean BAC of male drivers (1.42 mg/mL) was higher than that of female drivers (1.20 mg/mL). The mean age of male drivers (38) was also higher than that of female drivers (33). Distributions of vehicle types involved were studied. Cars had the highest percentage of occurrences (56.4%), followed by motorcycles (32.8%), electric bicycles (6.8%), trucks (1.5%), and bicycles (0.8%). It was found that these alcohol-related traffic crashes most often occurred between 7:00 p.m. and 10:59 p.m. , representing 48.1 percent (n = 590) of the 1226 cases. Single-vehicle crashes were overrepresented (70.3%) in all cases. The mean BAC in multivehicle crashes (1.69 mg/mL) was higher than that in single-vehicle crashes (1.30 mg/mL). Conclusions: The results indicated a notable need for more governmental attention that would prevent accidents caused by driving under the influence of alcohol.
Ectopic expression of murine CD47 minimizes macrophage rejection of human hepatocyte xenografts in immunodeficient mice

Macrophages play an important role in the rejection of xenogeneic cells and therefore represent a major obstacle to generating chimeric mice with human xenografts that are useful tools for basic and preclinical medical research. The signal inhibitory regulatory protein α (SIRPα) receptor is a negative regulator of macrophage phagocytic activity and interacts in a species‐specific fashion with its ligand CD47. Furthermore, SIRPα polymorphism in laboratory mouse strains significantly affects the extent of human CD47‐mediated toleration of human xenotransplants. Aiming to minimize macrophage activity and thus optimize human cell engraftment in immunodeficient mice, we lentivirally transduced murine CD47 (Cd47) into human liver cells. Human HepG2 liver cells expressing Cd47 were less frequently contacted and phagocytosed by murine RAW264.7 macrophages in vitro than their Cd47‐negative counterparts. For the generation of human‐mouse chimeric livers in immunodeficient BALB‐ΔRAG/γc‐uPA (urokinase‐type plasminogen activator) mice, freshly thawed cryopreserved human hepatocytes were transduced with a lentiviral expression vector for Cd47 using a refined in vitro transduction protocol immediately before transplantation. In vivo, Cd47‐positive human primary hepatocytes were selectively retained following engraftment in immunodeficient mice, leading to at least a doubling of liver repopulation efficiencies. Conclusion: We conclude that ectopic expression of murine Cd47 in human hepatocytes selectively favors engraftment upon transplantation into mice, a finding that should have a profound impact on the generation of robust humanized small animal models. Moreover, dominance of ectopically expressed murine Cd47 over endogenous human CD47 should also widen the spectrum of immunodeficient mouse strains suitable for humanization. (HEPATOLOGY 2012)
Fumarase: a paradigm of dual targeting and dual localized functions

The enzyme fumarase is a conserved protein in all organisms with regard to its sequence, structure and function. This enzyme participates in the tricarboxylic acid cycle in mitochondria which is essential for cellular respiration in eukaryotes. However, a common theme conserved from yeast to humans is the existence of a cytosolic form of fumarase; hence this protein is dual localized. We have coined identical (or nearly identical) proteins situated in different subcellular locations ‘echoforms’ or ‘echoproteins’. Fumarase was the first example of a dual localized protein whose mechanism of distribution was found to be based on a single translation product. Consequently, fumarase has become a paradigm for three unique eukaryotic cellular phenomena related to protein dual localization: (a) distribution between mitochondria and the cytoplasm involves reverse translocation; (b) targeting to mitochondria involves translation coupled import; and (c) there are two echoforms possessing distinct functions in the respective subcellular compartments. Here we describe and discuss these fumarase related phenomena and in addition point out approaches for studying dual function of distributed proteins, in particular compartment‐specific depletion. In the case of fumarase, the cytoplasmic function was only recently discovered; the enzyme was found to participate in the cellular response to DNA double strand breaks. Strikingly, upon DNA damage the protein is transported from the cytosol to the nucleus, where by virtue of its enzymatic activity it participates in the DNA damage response.
Quinolinic acid, the inescapable neurotoxin

Over the last two decades, evidence for the involvement of quinolinic acid (QUIN) in neuroinflammatory diseases has been exponentially increasing. Within the brain, QUIN is produced and released by infiltrating macrophages and activated microglia, the very cells that are prominent during neuroinflammation. QUIN acts as an agonist of the N‐methyl‐d‐aspartate receptor and as such is considered to be a brain endogenous excitotoxin. Since the discovery of the excitotoxic activity of QUIN in the early 1980s, several other cytotoxic mechanisms have been identified. We know today that QUIN acts as a neurotoxin, gliotoxin, proinflammatory mediator, pro‐oxidant molecule and can alter the integrity and cohesion of the blood–brain barrier. This paper aims to review some of the most recent findings about the effects of QUIN and its mode of action.
MicroRNA‐182 targets cAMP‐responsive element‐binding protein 1 and suppresses cell growth in human gastric adenocarcinoma

MicroRNAs (miRNAs) constitute a class of noncoding RNAs that post‐transcriptionally regulate gene expression. Recent evidence indicates that many miRNAs function as oncogenes or tumor suppressors by negatively regulating their target genes. In our previous study, using miRNA microarray analysis, we found that miRNA‐182 (miR‐182) was significantly downregulated in human gastric adenocarcinoma tissue samples. Here, we confirmed the downregulation of miR‐182 in a larger sample of gastric tissue samples. Overexpression of miR‐182 suppressed the proliferation and colony formation of gastric cancer cells. An oncogene, encoding cAMP‐responsive element binding protein 1 (CREB1), serves as a direct target gene of miR‐182. A fluorescent reporter assay confirmed that miR‐182 binds specifically to the predicted site of the CREB1 mRNA 3′‐UTR. When miR‐182 was overexpressed in gastric cancer cell lines, both the mRNA and protein levels of CREB1 were depressed. Furthermore, CREB1 was present at a high level in human gastric adenocarcinoma tissues, and this was inversely correlated with miR‐182 expression. Ectopic expression of CREB1 overcame the suppressive phenotypes of gastric cancer cells caused by miR‐182. These results indicate that miR‐182 targets the CREB1 gene and suppresses gastric adenocarcinoma cell growth, suggesting that miR‐182 shows tumor‐suppressive activity in human gastric cancer.
Risk Behaviors and HIV Infection in Alcohol/Drug Abuse: Indian Scenario

India ranks second among millions of HIV-infected people in Southeast Asia. Studies have pointed out various risk behaviors (injection- or sex-related) that contribute to HIV infection. The study aimed to examine the patterns of risk behaviors among opioid and alcohol dependence in two age groups and also to examine the prevalence of HIV seropositivity and its relationship with risk behaviors. One hundred fifty-four consecutive male patients of opioid/alcohol dependence syndrome were included in the study and analyzed in relation to their drug use pattern. Injection risk was significantly higher than sexual risk in both age groups, but the association of injection and sexual risk was significant in younger age group only. Sexual risk behaviors were higher in younger age group of HIV seropositives. There is a need to monitor the prevalence of HIV and promote interventions for safer sex in Indian setup.
Lumbar Spine Flexion And Extension Extremes Of Motion In Women Of Different Age And Racial Groups: 2603

Study Design—Observational. Objective—To provide normative values of lumbar flexion and extension for women of different age and racial groups. Summary of Background Data—Spinal range of motion (ROM) is one of the AMA Guides criteria used to estimate level of impairment and subsequent compensation entitlement. Studies show that spinal ROM varies with age, gender, and possibly race/ethnicity, but adequate normative values for different age and racial/ethnic groups do not exist. Methods—A cohort of free-living women was recruited for the Women's Injury Study at The Cooper Institute in Dallas. Originally, 917 women between the ages of 20 and 83 (M = 52 ± 13) underwent an orthopedic examination including lumbar spine flexion and extension measurement using an electronic inclinometer. Measurements were taken in the fully extended and flexed positions, respectively. This removes the influence of initial resting posture and is termed “extreme of motion” (EOM) as opposed to ROM. Age and racial groups were compared using a 2-way multivariate analysis of variance (MANOVA) followed with post hoc tests. Results—Means (±SD) were calculated for racial (white, N = 619, African-American, N = 147) and age groups (young, 20–39 years, n = 126; middle, 40–59 years, n = 412; older, ≥60 years, n = 228). Lumbar extension for African-American women (60.1°) was significantly greater (P < 0.05) than for white women (52.6°), but flexion was not different (15.2° and 17.0°), respectively. Extension EOM for the young group (61.6°) was greater (P < 0.05) than the middle (56.6°) and older (50.8°) groups. Extension difference between the middle and older groups was significant. Flexion EOM for the young group (20.1°) was greater (P < 0.05) than the middle (15.2°) and older (12.8°) groups. The difference in flexion between the middle and older groups was not significant. Conclusion—Normative values of lumbar extension are different for white and African-American women. Values for lumbar flexion and extension are different between age groups. Different criteria should be used to estimate impairment level in women of different racial and age groups.