Proteasome activity inhibition mediates endoplasmic reticulum stress-apoptosis in triptolide/lipopolysaccharide-induced hepatotoxicity.

Triptolide (TP) is a major active and toxic composition of the Chinese medicine Tripterygium wilfordii Hook. F. (TWHF), exhibiting various therapeutic bioactivities. Among the toxic effects, the hepatotoxicity of TP deserves serious attention. Previously, our research group proposed a new view of TP-related hepatotoxicity: hepatic hypersensitivity under lipopolysaccharide (LPS) stimulation. However, the mechanism of TP/LPS-induced hepatic hypersensitivity remains unclear. In this study, we investigated the mechanism underlying TP/LPS-induced hypersensitivity from the perspective of the inhibition of proteasome activity, activated endoplasmic reticulum stress (ERS)-related apoptosis, and the accumulation of reactive oxygen species (ROS). Our results showed that N-acetylcysteine (NAC), a common ROS inhibitor, decreased the expression of cleaved caspase-3 and cleaved PARP, which are associated with FLIP enhancement. Moreover, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was able to alleviate TP/LPS-induced hepatotoxicity by reducing ERS-related apoptosis protein expression (GRP78, p-eIF2α/eIF2α, ATF4, CHOP, cleaved caspase-3 and cleaved PARP) and ROS levels, with ATF4 being an indispensable mediator. In addition, the proteasome activity inhibitor MG-132 further aggravated ERS-related apoptosis, which indicated that the inhibition of proteasome activity also plays an important role in TP/LPS-related liver injuries. In summary, we propose that TP/LPS may upregulate the activation of ERS-associated apoptosis by inhibiting proteasome activity and enhancing ROS production through ATF4.

Spatiotemporal distribution of environmental microbiota around animal farms adjacent to produce fields in central coast California.

This study aimed to identify different environmental microbiota in animal farms adjacent to produce fields and to understand their potential flow pattern. Soil and water samples were collected from 16 locations during the winter, spring, summer, and fall seasons. In addition, a high-resolution digital elevation model helped to create a stream network to understand the potential flow of the microbiome. Metagenomic analysis of the 16 S rRNA gene revealed that soil and water samples from the four seasons harbor diverse microbiome profiles. The phylogenetic relationship of operational taxonomic units (OTUs) is separated by a maximum of 0.6 Bray-Curtis distance. Similarly, the Principal Component Analysis (P = 0.001) demonstrated the soil and water microbiome clustering across different locations and seasons. The relative abundance of Proteobacteria, Bacteroidetes, and Firmicutes was higher in the water samples than in the soil samples. In contrast, the relative abundance of Actinobacteria and Chloroflexi was higher in the soil compared to the water samples. Soil samples in summer and water samples in spring had the highest abundance of Bacteroidetes and Firmicutes, respectively. A unique microbial community structure was found in water samples, with an increased abundance of Hydrogenophaga and Solirubrobacter. Genera that were significantly abundant at a 1% false discovery rate (FDR) among seasons and soil or water samples, include Nocardioides, Gemmatimonas, JG30-KF-CM45, Massilia, Gaiellales, Sphingomonas, KD4-96, Bacillus, Streptomyces, Gaiella, and Gemmatimonadaceae. The relative abundance of pathogenic genera, including Mycobacterium, Bacteroides, Nocardia, Clostridium, and Corynebacterium, were significantly (at 1% FDR) affected by seasons and environmental type. The elevation-based stream network model suggests the potential flow of microbiomes from the animal farm to the produce fields.

Beyond the curriculum: unveiling medical students' drivers and barriers to research participation at Alfaisal University.

Medical education continually adapts to the needs of future health care professionals, with student motivation in research being a pivotal aspect. This study at Alfaisal University aimed to explore the motivations, benefits, and challenges faced by medical students in extracurricular research activities. Using a mixed-method approach, we combined quantitative surveys with qualitative group interviews. Findings revealed that both extrinsic (e.g., enhancing postgraduate training prospects) and intrinsic (e.g., personal interest and skill refinement) factors significantly motivate students to be involved in research activities. Participants unanimously acknowledged skill enhancement, particularly in literature comprehension, creative ideation, and networking. However, challenges such as conflicts with course scheduling, lack of hands-on experiences, and mentorship issues were identified as potential barriers to research participation. Addressing these barriers and understanding motivations can inform the design of research programs, enhancing the overall student research experience. This study underscores the importance of research in medical education, emphasizing the need for institutions to prioritize addressing challenges and leveraging benefits to prepare medical students for a research-integrated clinical future.NEW & NOTEWORTHY This article examines the motivating factors and obstacles of extracurricular research in Alfaisal University, Saudi Arabia. The study utilizes a mixed methodology of online surveys and in-person group interviews to gain insights from the medical students of the university. We revealed several extrinsic and intrinsic motivators that drove the students; however, there remain several challenges to students during their research journey. Addressing these challenges will help the students obtain a more fruitful, educational research experience.

The Remote Academic Radiologist: AJR Expert Panel Narrative Review.

The importance of developing a robust remote workforce in academic radiology has come to the forefront due to several converging factors. COVID-19, and the abrupt transformation it precipitated in terms of how radiologists worked, has been the biggest impetus for change; concurrent factors such as increasing examination volumes and radiologist burnout have also contributed. How to best advance the most desirable and favorable aspects of remote work while preserving an academic environment that fulfills the tripartite mission is a critical challenge that nearly all academic institutions face today. In this article, we discuss current challenges in academic radiology, including effects of the COVID-19 pandemic, from three perspectives-the radiologist, the learner, and the health system-addressing the following topics: productivity, recruitment, wellness, clinical supervision, mentorship and research, educational engagement, radiologist access, investments in technology, and radiologist value. Throughout, we focus on the opportunities and drawbacks of remote work, to help guide its effective and reliable integration into academic radiology practices.

The incidence of radiation-induced moyamoya among pediatric brain tumor patients who received photon radiation versus those who received proton beam therapy: a systematic review.

Cranial irradiation is associated with several adverse events such as endocrinopathy, growth retardation, neurocognitive impairment, secondary malignancies, cerebral vasculopathy, and potential stroke. The better side effects profile of proton beam therapy compared with that of photon radiation therapy is due to its physical properties, mainly the sharp dose fall-off after energy deposition in the Bragg peak. Despite the better toxicity profile of proton beam therapy, the risk of  moyamoya syndrome still exists. We conducted a systematic review of the existing literature on moyamoya syndrome after receiving cranial radiation therapy for pediatric brain tumors to investigate the incidence of moyamoya syndrome after receiving photon versus proton radiation therapy. In this review, we report that the incidence of moyamoya syndrome after receiving proton beam therapy is almost double that of photon-induced moyamoya syndrome. Patients who received proton beam therapy for the management of pediatric brain tumors are more likely to develop moyamoya syndrome at the age of less than 5 years. Meanwhile, most patients with proton-induced moyamoya are more likely to be diagnosed within the first 2 years after the completion of their proton beam therapy.

Surgical treatment of craniocervical instability: comparison of two constructs regarding clinical and radiological outcomes of 100 patients.

PURPOSE: There is an increased demand for surgical solutions to treat craniocervical instability. This retrospective study demonstrates the clinical and radiological outcomes of unstable craniocervical junction treated with occipitocervical fusion. MATERIAL AND METHODS: The mean age of 52 females and 48 males was 56.89 years. The clinical and radiological outcomes were assessed, including NDI, VAS, ASIA score, imaging, complications and bony fusion in two used constructs: a modern occipital plate-rod-screw system (n = 59) and previous bilateral contoured titanium reconstruction plates-screws (n = 41). RESULTS: Clinically and on imaging, patients presented with neck pain, myelopathy, radiculopathy, vascular symptoms and craniocervical instability. The mean follow-up was 6.47 years. A solid bony fusion was achieved in 93.81% of the patients. The NDI and the VAS improved significantly from 28.3 and 7.67 at the presentation to 16.2 and 3.47 at the final follow-up. The anterior and posterior atlantodental interval (AADI and PADI), the clivus canal angle (CCA), the occipitoaxial angle (OC2A) and the posterior occipitocervical angle (POCA) improved significantly. Six patients required early revision. CONCLUSION: Occipitocervical fusion can yield excellent results regarding clinical improvement and long-term stability with a high fusion rate. Simple reconstruction plates, though more demanding surgically, achieve similar results. Preserving a neutral patient's position for fixation avoids postoperative dysphagia and may help prevent adjacent segment disease development.

Challenges in the Head and Neck Department in the Diagnosis and Surgical Treatment of Patients Presenting to a Single Tertiary Hospital of Somalia With Extreme War Injuries.

In this study, the authors aimed to share their experience with 46 patients who were wounded due to terrorism and war in Somalia. The authors also evaluated the etiological diversity of terror-related and war-related injuries. The study included 46 patients treated at the 150-bed Turkey-Somalia Tertiary Hospital between 2019 and 2021. The authors reviewed medical records including data regarding age, sex, trauma etiology, and type of fracture and trauma. For all patients, surgical technique and plate and screw applications were recorded. The authors also assessed complications and outcomes for the patients. The study included 5 women (10.9%) and 41 men (89.1%). The mean age was 30.36 years. It was found that 2 patients (4.35%) presented to the emergency department with stab injuries, 33 patients with blast injuries from improvised explosive devices (71.73%), and 11 patients with firearm injuries. There were 31 patients with maxillary and mandibular fractures, 17 of which had both maxillary and mandibular fractures. There were 14 patients with maxillary fracture alone, including 3 patients with tripod fracture and 7 patients with inferior and lateral rim fracture. There was a mandibular fracture in 17 patients, including 5 patients with parasymphysis fracture, 7 patients with ramus fracture, and 5 patients with multifocal comminuted fracture. It is a challenging process to treat terror-related injuries in our tertiary hospital in Somalia, where all resources are imported from foreign countries. In such settings, authorities should make protective equipment obligatory to prevent civil and military casualties. Trauma hospitals and experienced trauma surgeons should be available.

Intuitive evaluation of contemporary management strategies in thymoma - the largest Indian experience.

Background: The aim was perusal of the treatment strategies, clinical outcomes and factors impacting these outcomes in thymoma. Materials and methods: A total of 119 patients diagnosed and treated cases of thymoma, at our hospital, were taken for analysis. Thirty-one patients were excluded due to inadequate medical records. Descriptive statistics were used to report demographic and clinical characteristics. Time period between diagnosis and death was defined as overall survival (OS). Multivariate analysis (MVA), using cox regression modelling, was done by including clinicopathological factors in a bid to identify prognostic factors influencing OS. SPSS version 26 was used for statistical analysis. Results: The mean age of the patients was 52.17 years and 39 (44.3%), 19 (21.6%), 17 (1.3%) and 13 (4.8%) patients presented with Masaoka stage II, IV, III and I, respectively. Surgery was done in 64 (72.7%) of the patients as a part of the treatment strategy. Radiotherapy was administered to a total of 57 patients with a median dose of 50.4 Gy. Early Masaoka stage at presentation and use of surgery in the treatment plan were statistically significant prognostic factors for a better overall survival on multivariate analysis. Conclusion: Judicious use of radiotherapy and chemotherapy in locally advanced cases may render them resectable. In a bid to gain good survival rates, aggressive multimodality treatment should be offered to the patients.

Dietary fat composition shapes bile acid metabolism and severity of liver injury in a pig model of pediatric NAFLD.

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.NEW & NOTEWORTHY Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS: We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS: There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40- to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40- to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS: Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade.

Collaborative care model for diabetes in primary care settings in Qatar: a qualitative exploration among healthcare professionals and patients who experienced the service.

BACKGROUND: Diabetes mellitus is highly prevalent and associated with huge economic burden globally. The conventional care and management of diabetes mellitus is highly fragmented and complex, warranting the need for a comprehensive Collaborative Care Model (CCM). Little is known about the perception of patients with diabetes and their healthcare providers about CCM, its barriers and facilitators. This study aimed to explore the value of CCM in diabetes care at a primary healthcare (PHC) setting from the perspective of patients with diabetes and healthcare professionals (HCPs), in an effort to expand our current knowledge on collaborative care in diabetes at primary care level for the purpose of quality improvement and service expansion. METHODS: Using an exploratory case study approach, semi-structured interviews were conducted among patients and HCPs who encountered CCM in Qatar during 2019 and 2020. The semi-structured interviews were transcribed verbatim and the data were analysed and interpreted using a deductive-inductive thematic analysis approach. RESULTS: Twelve patients and 12 HCPs at a diabetes clinic participated in one-to-one interviews. The interviews resulted in five different themes: the process and components of collaborative care model (four subthemes), current organizational support and resources (three subthemes), impact of collaborative care model on diabetes outcomes (three subthemes), enablers of collaborative care model (three subthemes), and barriers to collaborative care model (three subthemes). The participants indicated easy access to and communication with competent and pleasant HCPs. The patients appreciated the extra time spent with HCPs, frequent follow-up visits, and health education, which empowered them to self-manage diabetes. HCPs believed that successful CCM provision relied on their interest and commitment to care for patients with diabetes. Generally, participants identified barriers and facilitators that are related to patients, HCPs, and healthcare system. CONCLUSIONS: The providers and users of CCM had an overall positive perception and appreciation of this model in PHC settings. Barriers to CCM such as undesirable attributes of HCPs and patients, unsupportive hospital system, and high workload must be addressed before implementing the model in other PHC settings.

Elemental analysis of soils along the South African National Road (N3) - a combined approach including statistics, pollution indicators, and geographic information system (GIS).

The South African National Road (N3) in the KwaZulu-Natal province is one of the major transportation routes from the Durban harbor. In this study, metal concentrations in Bidens pilosa L., which grows alongside the N3, and soil were determined using inductively coupled plasma - optical emission spectrometry to evaluate the impact of soil quality on the uptake. Furthermore, the distribution of Pb and Cd was mapped using the geographic information system (GIS) approach to identify the potential benefits of spatial data applications in soil studies. Plant concentrations of toxic metals, especially Pb, were high and were linked to high soil concentrations. The target hazard quotients indicated a low risk of adverse effects due to Cd exposure and increased risk due to As and Pb exposure. The carcinogenic risk was high for As and Cd exposure at all sites and Pb at 40% of the sites. Soil quality indicators (geoaccumulation indices and enrichment factors) showed soils to be moderate to heavily contaminated. Principal component analysis indicated different anthropogenic sources of contamination, including vehicular emissions and a combination of industrial, agricultural, and social impacts. Kriging interpolation depicted the spatial diffusion of Cd and Pb concentrations throughout the study area with different hot-spot areas of metal contamination for these two metals. The study demonstrated that the plants growing along national roads are not suitable for human consumption.

Neurodegeneration in juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease.

The objective of this study was to investigate whether juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease (NAFLD), cholestasis, and gut dysbiosis would develop histological and metabolic markers of neurodegeneration in the frontal cortex (FC) and whether supplementing probiotics would influence the response to the diet. Twenty-eight juvenile Iberian pigs were fed for 10 wk either a control (CON) or high-fructose high-fat (HFF) diet with or without a commercial probiotic mixture. Compared with CON, HFF-fed pigs had a decreased number of neurons and an increase in reactive astrocytes in FC tissue. There was also a decrease in one-carbon metabolites choline and betaine and a marked accumulation of bile acids, cholesteryl esters, and polyol pathway intermediates in FC of HFF-fed pigs, which were associated with markers of neurodegeneration and accentuated with the severity of NAFLD. Betaine depletion in FC tissue was negatively correlated with choline-derived phospholipids in colon content, whereas primary conjugated bile acids in FC were associated with cholestasis. Plasma kynurenine-to-tryptophan quotient, as a marker of indoleamine 2,3-dioxygenase activity, and intestinal dysbiosis were also correlated with neuronal loss and astrogliosis. Recognition memory test and FC levels of amyloid-ß and phosphorylated Tau did not differ between diets, whereas probiotics increased amyloid-ß and memory loss in HFF-fed pigs. In conclusion, our results show evidence of neurodegeneration in FC of juvenile Iberian pigs and establish a novel pediatric model to investigate the role of gut-liver-brain axis in diet-induced NAFLD.

Intermittent leucine pulses during continuous feeding alters novel components involved in skeletal muscle growth of neonatal pigs.

When neonatal pigs continuously fed formula are supplemented with leucine pulses, muscle protein synthesis and body weight gain are enhanced. To identify the responsible mechanisms, we combined plasma metabolomic analysis with transcriptome expression of the transcriptome and protein catabolic pathways in skeletal muscle. Piglets (n = 23, 7-day-old) were fed continuously a milk replacement formula via orogastric tube for 21 days with an additional parenteral infusion (800 µmol kg-1 h-1) of either leucine (LEU) or alanine (CON) for 1 h every 4 h. Plasma metabolites were measured by liquid chromatography-mass spectrometry. Gene and protein expression analyses of longissimus dorsi muscle were performed by RNA-seq and Western blot, respectively. Compared with CON, LEU pigs had increased plasma levels of leucine-derived metabolites, including 4-methyl-2-oxopentanoate, beta-hydroxyisovalerate, ß-hydroxyisovalerylcarnitine, and 3-methylglutaconate (P ≤ 0.05). Leucine pulses downregulated transcripts enriched in the Kyoto Encyclopedia of Genes and Genomes terms "spliceosome," "GAP junction," "endocytosis," "ECM-receptor interaction," and "DNA replication". Significant correlations were identified between metabolites derived from leucine catabolism and muscle genes involved in protein degradation, transcription and translation, and muscle maintenance and development (P ≤ 0.05). Further, leucine pulses decreased protein expression of autophagic markers and serine/threonine kinase 4, involved in muscle atrophy (P ≤ 0.01). In conclusion, results from our studies support the notion that leucine pulses during continuous enteral feeding enhance muscle mass gain in neonatal pigs by increasing protein synthetic activity and downregulating protein catabolic pathways through concerted responses in the transcriptome and metabolome.

Gram-scale synthesis of alkoxide-derived nitrogen-doped carbon foam as a support for Fe-N-C electrocatalysts.

Non-platinum group metal (non-PGM) catalysts for the oxygen reduction reaction (ORR) are set to reduce the cost of polymer electrolyte membrane fuel cells (PEFCs) by replacing platinum at the cathode. We previously developed unique nitrogen-doped carbon foams by template-free pyrolysis of alkoxide powders synthesized using a high temperature and high pressure solvothermal reaction. These were shown to be effective ORR electrocatalysts in alkaline media. Here, we present a new optimised synthesis protocol which is carried out at ambient temperature and pressure, enabling us to safely increase the batch size to 2 g, increase the yield by 60%, increase the specific surface area to 1866 m2 g-1, and control the nitrogen content (between 1.0 and 5.2 at%). These optimized nitrogen-doped carbon foams are then utilized as effective supports for Fe-N-C catalysts for the ORR in acid media, whilst multiphysics modelling is used to gain insight into the electrochemical performance. This work highlights the importance of the properties of the carbon support in the design of Pt-free electrocatalysts.

Parosteal Osteosarcoma of the Proximal Phalanx of a Finger.

Osteogenic sarcoma of the hand is very rare and fewer than 50 cases have been reported. There are only 2 previously reported cases of parosteal osteosarcoma involving the phalanges. We report a primary parosteal osteosarcoma involving the proximal phalanx of the right middle finger in a 20-year-old woman, which was managed by ray amputation. There was no evidence of local recurrence or systemic metastasis in the postoperative follow-up period of 2 years.

Maintenance of Segmental Maxillary Expansion: The Use of Custom, Virtually Designed, and Manufactured Palatal Appliances Without the Use of an Occlusal Splint.

Expansion of the maxilla using a segmental Le Fort I osteotomy is a routine and commonly used procedure in the treatment of dentofacial deformities. Although orthognathic surgery has seen tremendous advancement in technology, including virtual surgical planning and customized hardware, some room for advancement exists in the maintenance of surgical maxillary expansion. Traditionally, this has been accomplished with retention of a maxillary occlusal splint 4 to 8 weeks postoperatively. This article introduces some novel techniques to help maintain this expansion, including the intraoperative transpalatal archwire and custom palatal strap appliance in conjunction with autogenous bone harvest and grafting in lieu of using occlusal-based splints. The aim of these techniques is to improve postoperative patient comfort and surgical outcomes and shorten postoperative orthodontic treatment time.

Tyrosine phosphorylation stimulates activity of human RAD51 recombinase through altered nucleoprotein filament dynamics.

The DNA strand exchange protein RAD51 facilitates the central step in homologous recombination, a process fundamentally important for accurate repair of damaged chromosomes, restart of collapsed replication forks, and telomere maintenance. The active form of RAD51 is a nucleoprotein filament that assembles on single-stranded DNA (ssDNA) at the sites of DNA damage. The c-Abl tyrosine kinase and its oncogenic counterpart BCR-ABL fusion kinase phosphorylate human RAD51 on tyrosine residues 54 and 315. We combined biochemical reconstitutions of the DNA strand exchange reactions with total internal reflection fluorescence microscopy to determine how the two phosphorylation events affect the biochemical activities of human RAD51 and properties of the RAD51 nucleoprotein filament. By mimicking RAD51 tyrosine phosphorylation with a nonnatural amino acid, p-carboxymethyl-l-phenylalanine (pCMF), we demonstrated that Y54 phosphorylation enhances the RAD51 recombinase activity by at least two different mechanisms, modifies the RAD51 nucleoprotein filament formation, and allows RAD51 to compete efficiently with ssDNA binding protein RPA. In contrast, Y315 phosphorylation has little effect on the RAD51 activities. Based on our work and previous cellular studies, we propose a mechanism underlying RAD51 activation by c-Abl/BCR-ABL kinases.

Anthropometric Analysis of Secondary Cleft Lip Rhinoplasty Using Costal Cartilage Graft.

Despite the improvement of primary repair of nasal deformities during the management of cleft lip in infancy, this does not exclude the need for revision rhinoplasty in adulthood for complete patients' rehabilitation. The purpose of this study was to evaluate the aesthetic outcome of secondary rhinoplasty using costal cartilage grafts in patients with unilateral cleft lip nasal deformity. Twenty patients who were operated at earlier ages for correction of cleft lip and had a residual unilateral cleft lip nasal deformity were included in this study. Costal cartilage rib grafts were harvested; carved and used for maxillary augmentation, columellar strut graft, and lateral crural strut graft. Five anthropometric measurements (nostril height, width and gap area, columellar axis deviation angle and nasal base inclination angle) were used for evaluation of aesthetic results. The ratio of nostril width, height and gap area between the cleft side and the non-cleft side showed significant improvement (P <0.05). The columellar axis deviation showed significant improvement towards the midline (P = 0.004), and the alar base inclination showed improvement towards the horizontal line (P = 0.0045). In conclusion, the aesthetic outcomes of secondary cleft lip rhinoplasty using the costal cartilage are satisfactory. The costal cartilage has the required strength, is easily carved and maintains shape for considerable time.

Genome-wide association scan for heterotic quantitative trait loci in multi-breed and crossbred beef cattle.

BACKGROUND: Heterosis has been suggested to be caused by dominance effects. We performed a joint genome-wide association analysis (GWAS) using data from multi-breed and crossbred beef cattle to identify single nucleotide polymorphisms (SNPs) with significant dominance effects associated with variation in growth and carcass traits and to understand the mode of action of these associations. METHODS: Illumina BovineSNP50 genotypes and phenotypes for 11 growth and carcass traits were available for 6796 multi-breed and crossbred beef cattle. After performing quality control, 42,610 SNPs and 6794 animals were used for further analyses. A single-SNP GWAS for the joint association of additive and dominance effects was conducted in purebred, crossbred, and combined datasets using the ASReml software. Genomic breed composition predicted from admixture analyses was included in the mixed effect model to account for possible population stratification and breed effects. A threshold of 10% genome-wide false discovery rate was applied to declare associations as significant. The significant SNPs with dominance association were mapped to their corresponding genes at 100 kb. RESULTS: Seven SNPs with significant dominance associations were detected for birth weight, weaning weight, pre-weaning daily gain, yearling weight and marbling score across the three datasets at a false discovery rate of 10%. These SNPs were located on bovine chromosomes 1, 3, 4, 6 and 21 and mapped to six putative candidate genes: U6atac, AGBL4, bta-mir-2888-1, REPIN1, ICA1 and NXPH1. These genes have interesting biological functions related to the regulation of gene expression, glucose and lipid metabolism and body fat mass. For most of the identified loci, we observed over-dominance association with the studied traits, such that the heterozygous individuals at any of these loci had greater genotypic values for the trait than either of the homozygous individuals. CONCLUSIONS: Our results revealed very few regions with significant dominance genetic effects across all the traits studied in the three datasets used. Regarding the SNPs that were detected with dominance associations, further investigation is needed to determine their relevance in crossbreeding programs assuming that dominance effects are the main cause of (or contribute usefully to) heterosis.