Nucleolar localization of an isoform of the IGF-I precursor

BACKGROUND: Alternative exons encode different isoforms of the human insulin-like growth factor-I (IGF-I) precursor without altering mature IGF-I. We hypothesized that the various IGF-I precursors may traffic IGF-I differently. Chimeric IGF-I precursors were made with green fluorescent protein (GFP) cloned between the signal and mature IGF-I domains. RESULTS: Chimeras containing exons 1 or 2 were located in the cytoplasm, consistent with a secretory pathway, and suggesting that both exons encoded functional signal peptides. Exon 5-containing chimeras localized to the nucleus and strongly to the nucleolus, while chimeras containing exon 6 or the upstream portion of exon 5 did not. Nuclear and nucleolar localization also occurred when the mature IGF-I domain was deleted from the chimeras, or when signal peptides were deleted. CONCLUSIONS: We have identified a nucleolar localization for an isoform of the human IGF-I precursor. The findings are consistent with the presence of a nuclear and nucleolar localization signal situated in the C-terminal part of the exon 5-encoded domain with similarities to signals in several other growth factors

Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine MONOCLONAL ANTIBODIES (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection IN VITRO (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S PROTEIN at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.published_or_final_versio

Mirizzi syndrome associated with hepatic artery pseudoaneurysm: a case report.

INTRODUCTION: This is the first case report of Mirizzi syndrome associated with hepatic artery pseudoaneurysm. CASE PRESENTATION: A 54-year-old man presented with painful obstructive jaundice and weight loss. Computed tomography showed a hilar mass in the liver. Following an episode of haemobilia, angiography demonstrated a pseudoaneurysm of a branch of the right hepatic artery that was embolised. At surgery, a gallstone causing Mirizzi type II syndrome was found to be responsible for the biliary obstruction and a necrotic inflammatory mass and haematoma were found to be extending into the liver. The mass was debrided and drained, the obstructing stones removed and the bile duct drained with a t-tube. The patient made a full recovery. CONCLUSION: This case highlights another situation where there may be difficulty in differentiating Mirizzi syndrome from biliary tract cancer.Published versio

Red pigment from Saw Palmetto: a natural product for potential alternative cancer treatment

Conference Theme: Anticancer Drug Action and Drug Resistance: from Cancer Biology to the ClinicINTRODUCTION: Saw palmetto is extract of the fruit of Serenoa repens (Bartram) J.K.Small, an edible plant originated from the Southeastern United States. It has been used in traditional, complementary and alternative medicine as a tonic, expectorant and antiseptic for treatment of various illnesses, especially urinary and reproductive system problems. Approximately 90% of Saw palmetto containing fatty acids and has been claimed for its therapeutic effect on benign prostatic hyperplasia (BPH). Previous studies also suggested the in vitro and in vivo anti-cancer effect of lipidosterolic extract of Saw Palmetto. However, recent epidemiology and randomized trials ...published_or_final_versio

Asian “Guan” Parenting and Life Satisfaction Among Adolescents in Malaysia: The Mediating Role of Filial Piety

Literature on adolescent development has shown that parenting practices have positive relationships with adolescents’ life satisfaction. Adolescents’ life satisfaction improves when they have parents low in psychological control who uphold reciprocal self-disclosure in their communication. Guan parenting was found to correlate positively with adolescents’ development. Therefore, it is methodologically important to replicate the investigation on the relationship between adolescents’ life satisfaction and Guan parenting. Literature suggests that filial piety is shaped by parenting practices and adolescents who perceived intense parental concern, care, and involvement tend to uphold filial piety and express gratitude toward parents which may promote the adolescents’ life satisfaction. In this study, mediation analysis was done to elucidate the relationship among parents’ guan parenting style, filial piety, and life satisfaction on 606 adolescents (Mage=15.07; SDage=1.03; 52.1% females) in Malaysia. The adolescents were sampled through cluster sampling, and data were collected using self-administered questionnaires. The results showed positive relationship between paternal and maternal guan parenting with filial piety and adolescents’ life satisfaction. Greater parents’ filial piety was linked to higher life satisfaction among adolescents. Findings from the mediation models indicated the association among guan parenting with filial piety, gratitude toward parents, and higher life satisfaction. The findings also offered empirical evidence to the underlying mechanism of how guan parenting could affect adolescent life satisfaction via the mediating role of filial piety. The findings also supported the importance of culture-infused parenting in inculcating adolescents’ filial piety besides establishing its link to life satisfaction in Asian families

Sustainable construction and the versatility of the quantity surveying profession in Singapore

Purpose The changing role of quantity surveyors in the new paradigm of sustainable construction requires studies into new competencies and skills for the profession. The impact of sustainable construction on quantity surveying services, engagement and how they manage challenges provided an indication of the success indicators of the quantity surveying profession in meeting the sustainable construction needs. Design/methodology/approach A five-point Likert scale was developed from the list of quantity surveying firms in Singapore. An 85% response rate from 60 quantity surveying firms contacted in this study provided 51 responses. Descriptive statistics and factor analysis were employed to evaluate the findings. Findings The factor analysis categorised the drivers derived from the literature into awareness of sustainable construction, adversarial role on green costing; carbon cost planning; valuing a sustainable property; common knowledge of sustainable construction; and lack of experience in sustainable construction. Social implications The research findings supported the idea of increased sustainable construction skills in quantity surveying education, research and training. Originality/value The dearth of quantity surveyors with sustainable construction experience must focus on quantity surveying professional bodies and higher education. The quantity surveying profession needs reskilling in green costing and carbon cost planning to meet the needs of sustainable construction

A comparison of surgical outcomes between endoscopic and robotically assisted thyroidectomy: the authors’ initial experience

Background: The gasless, transaxillary endoscopic thyroidectomy (GTET) offers a distinct advantage over the conventional open operation by leaving no visible neck scar, and in an attempt to improve its ergonomics and surgical outcomes, the robotically assisted thyroidectomy (RAT) was introduced. The RAT uses the same endoscopic route as the GTET but with the assistance of the da Vinci S robotic system. Excellent results for RAT have been reported, but it remains unclear whether RAT offers any potential benefits over GTET. Methods: From June to December 2009, 46 patients underwent endoscopic thyroidectomy. Of these patients, 39 had surgery without the robot (GTET) and 7 had surgery with the robot (RAT). Demographics, surgical indications, operative findings, and postoperative outcomes were compared between the two groups. All the patients were followed up for at least 6 months after surgery. Results: Patient demographics, surgical indications, and extent of resection were similar between the two groups. The median total procedure time was significantly longer for RAT (149 min) than for GTET (100 min; p = 0.018), but the contralateral recurrent laryngeal nerve was more likely to identified in RAT (100%) than in GTET (42.9%; p = 0.070). On the average, GTET needed one more surgical assistant than RAT (1 vs. 0; ppublished_or_final_versionSpringer Open Choice, 21 Feb 201

Genome characterization and taxonomy of <em>Actinomyces acetigenes</em> sp. nov., and <em>Actinomyces stomatis</em> sp. nov., previously isolated from the human oral cavity

\ua9 2023, The Author(s).Background: Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital tract. Understanding the diversity and characterization of Actinomyces species is crucial for human health, as they play an important role in dental plaque formation and biofilm-related infections. Two Actinomyces strains ATCC 49340 T and ATCC 51655 T have been utilized in various studies, but their accurate species classification and description remain unresolved. Results: To investigate the genomic properties and taxonomic status of these strains, we employed both 16S rRNA Sanger sequencing and whole-genome sequencing using the Illumina HiSeq X Ten platform with PE151 (paired-end) sequencing. Our analyses revealed that the draft genome of Actinomyces acetigenes ATCC 49340 T was 3.27 Mbp with a 68.0% GC content, and Actinomyces stomatis ATCC 51655 T has a genome size of 3.08 Mbp with a 68.1% GC content. Multi-locus (atpA , rpoB, pgi , metG , gltA , gyrA, and core genome SNPs) sequence analysis supported the phylogenetic placement of strains ATCC 51655 T and ATCC 49340 T as independent lineages. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI) analyses indicated that both strains represented novel Actinomyces species, with values below the threshold for species demarcation (70% dDDH, 95% ANI and AAI). Pangenome analysis identified 5,731 gene clusters with strains ATCC 49340 T and ATCC 51655 T possessing 1,515 and 1,518 unique gene clusters, respectively. Additionally, genomic islands (GIs) prediction uncovered 24 putative GIs in strain ATCC 49340 T and 16 in strain ATCC 51655 T, contributing to their genetic diversity and potential adaptive capabilities. Pathogenicity analysis highlighted the potential human pathogenicity risk associated with both strains, with several virulence-associated factors identified. CRISPR-Cas analysis exposed the presence of CRISPR and Cas genes in both strains, indicating these strains might evolve a robust defense mechanism against them. Conclusion: This study supports the classification of strains ATCC 49340 T and ATCC 51655 T as novel species within the Actinomyces, in which the name Actinomyces acetigenes sp. nov. (type strain ATCC 49340 T = VPI D163E-3 T = CCUG 34286 T = CCUG 35339 T) and Actinomyces stomatis sp. nov. (type strain ATCC 51655 T = PK606T = CCUG 33930 T) are proposed