1,339 research outputs found
Generational Career Shifts: how Matures, Boomers, Gen Xers, and Millennials view work
We examined several career concepts, including career identity, planning and resilience, career salience, work locus of control, modern career orientations, career self-efficacy, and career anchors, as well as the expectations of pre-career Millennials. Overall, our study shows significant intergenerational differences across many of these concepts. For example, Matures identified with their careers more than other generations, which suggests that work plays a more central role in their lives. Millennials and Gen X employees indicated a belief that they are not in control of their career success. Moreover, Millennials had lower levels of selfefficacy than both Gen X and Boomer employees. In terms of career anchors, we found that each successive younger generation placed more importance on autonomy and independence, entrepreneurial creativity, lifestyle, service, and dedication. Lastly, pre-career Millennials indicated high expectations for salary growth over their careers, despite expecting to take an average of five years off of work for child-rearing and travel activities
Unintended Consequences of Interview Faking: Impact on Perceived Fit and Affective Outcomes
Drawing on signalling theory, we propose that use of deceptive impression management (IM) in the employment interview could produce false signals, and individuals hired based on such signals may incur consequences once they are on the job—such as poor perceived fit. We surveyed job applicants who recently interviewed and received a job to investigate the relationship between use of deceptive IM in the interview and subsequent perceived personjob and person-organization fit, stress, well-being, and employee engagement. In a twophase study, 206 job applicants self-reported their use of deceptive IM in their interviews at Time 1, and their perceived person–job and person–organization fit, job stress, affective well-being, and employee engagement at Time 2. Deceptive IM had a negative relationship with perceived person–job and person–organization fit. As well, perceived fit accounted for the relationship between deceptive IM and well-being, employee engagement, and job stress. The findings indicate that using deceptive IM in the interview may come at a cost to employees
Trusting Robocop: Gender-Based Effects on Trust of an Autonomous Robot
Little is known regarding public opinion of autonomous robots. Trust of these robots is a pertinent topic as this construct relates to one’s willingness to be vulnerable to such systems. The current research examined gender-based effects of trust in the context of an autonomous security robot. Participants (N = 200; 63% male) viewed a video depicting an autonomous guard robot interacting with humans using Amazon’s Mechanical Turk. The robot was equipped with a non-lethal device to deter non-authorized visitors and the video depicted the robot using this non-lethal device on one of the three humans in the video. However, the scenario was designed to create uncertainty regarding who was at fault – the robot or the human. Following the video, participants rated their trust in the robot, perceived trustworthiness of the robot, and their desire to utilize similar autonomous robots in several different contexts that varied from military use to commercial use to home use. The results of the study demonstrated that females reported higher trust and perceived trustworthiness of the robot relative to males. Implications for the role of individual differences in trust of robots are discussed
Associations Between MRI-Assessed Locus Coeruleus Integrity and Cortical Gray Matter Microstructure
The locus coeruleus (LC) is one of the earliest sites of tau pathology, making it a key structure in early Alzheimer's disease (AD) progression. As the primary source of norepinephrine for the brain, reduced LC integrity may have negative consequences for brain health, yet macrostructural brain measures (e.g. cortical thickness) may not be sensitive to early stages of neurodegeneration. We therefore examined whether LC integrity was associated with differences in cortical gray matter microstructure among 435 men (mean age = 67.5; range = 62-71.7). LC structural integrity was indexed by contrast-to-noise ratio (LCCNR) from a neuromelanin-sensitive MRI scan. Restriction spectrum imaging (RSI), an advanced multi-shell diffusion technique, was used to characterize cortical microstructure, modeling total diffusion in restricted, hindered, and free water compartments. Higher LCCNR (greater integrity) was associated with higher hindered and lower free water diffusion in multiple cortical regions. In contrast, no associations between LCCNR and cortical thickness survived correction. Results suggest lower LC integrity is associated with patterns of cortical microstructure that may reflect a reduction in cytoarchitectural barriers due to broader neurodegenerative processes. These findings highlight the potential utility for LC imaging and advanced diffusion measures of cortical microstructure in assessing brain health and early identification of neurodegenerative processes
Trace elements at the intersection of marine biological and geochemical evolution
Life requires a wide variety of bioessential trace elements to act as structural components and reactive centers in metalloenzymes. These requirements differ between organisms and have evolved over geological time, likely guided in some part by environmental conditions. Until recently, most of what was understood regarding trace element concentrations in the Precambrian oceans was inferred by extrapolation, geochemical modeling, and/or genomic studies. However, in the past decade, the increasing availability of trace element and isotopic data for sedimentary rocks of all ages has yielded new, and potentially more direct, insights into secular changes in seawater composition – and ultimately the evolution of the marine biosphere. Compiled records of many bioessential trace elements (including Ni, Mo, P, Zn, Co, Cr, Se, and I) provide new insight into how trace element abundance in Earth's ancient oceans may have been linked to biological evolution. Several of these trace elements display redox-sensitive behavior, while others are redox-sensitive but not bioessential (e.g., Cr, U). Their temporal trends in sedimentary archives provide useful constraints on changes in atmosphere-ocean redox conditions that are linked to biological evolution, for example, the activity of oxygen-producing, photosynthetic cyanobacteria. In this review, we summarize available Precambrian trace element proxy data, and discuss how temporal trends in the seawater concentrations of specific trace elements may be linked to the evolution of both simple and complex life. We also examine several biologically relevant and/or redox-sensitive trace elements that have yet to be fully examined in the sedimentary rock record (e.g., Cu, Cd, W) and suggest several directions for future studies
Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers
ADDITIONAL FILE 1: FIGURE S1. Concordant SV call generation from Manta
and GRIDSS. FIGURE S2. Summary of SVs in each type, compared to other
studies. FIGURE S3. CIRCOS plot of hyper-SV mutated tumours. FIGURE S4. The spread of SV breakpoints and samples in each 1 Mbp genomic bin. FIGURE S5. TMPRSS2-ERG fusion with interstitial region retention.
TABLE S1. Clinical and pathological characteristics of 180 prostate cancer
patients included in this study. TABLE S2. Biallelic assessment of CDK12
in hyper-duplicated samples. TABLE S3. Biallelic assessment of BRCA2 in
hyper-deleted samples.ADDITIONAL FILE 2: TABLE S4. Summary of gene fusions identified from SVs.
ADDITIONAL FILE 3: TABLE S5. SV calls resulting in gene fusions.DATA AND MATERIALS AVAILABILITY : The datasets analysed in this study were obtained and accessible through
Jaratlerdsiri et al [6], with sequence data deposited in the European GenomePhenome Archive (EGA; https://ega-archive.org) under overarching accession
EGAS00001006425 and including the Southern African Prostate Cancer Study
(SAPCS) Dataset (EGAD00001009067) and Garvan/St Vincent’s Prostate Cancer
Database (EGAD00001009066). The computational code used to analyse SV
subtypes, SV hotspots and gene fusions is available on GitHub [68].BACKGROUND : African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-
Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the
benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa
genomic studies are still biased towards small variant interrogation.
METHODS : Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis
of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four
ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity
(African versus European), with a focus on African men from southern Africa.
RESULTS : Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count)
increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation
and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived
tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion
subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate
in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion
partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV
hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic
implications for African patients.
CONCLUSIONS : In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation
for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs
in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed
ethnic disparity in advanced PCa presentation in men of African ancestry.The Medical Health and Medical Research Council (NHMRC) of Australia, University of Sydney Bridging Grant, the USA. Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Idea Development.https://genomemedicine.biomedcentral.comam2023School of Health Systems and Public Health (SHSPH
Application of In Vivo Induced Antigen Technology (IVIAT) to Bacillus anthracis
In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced expression in vivo for a subset of B. anthracis genes identified by IVIAT, including L-alanine amidases BA3767, BA4073, and amiA (pXO2-42); the bacteriophage holin gene BA4074; and pagA (pXO1-110). The exogenous addition of two purified putative autolysins identified by IVIAT, N-acetylmuramoyl-L-alanine amidases BA0485 and BA2446, to vegetative B. anthracis cell suspensions induced a species-specific change in bacterial morphology and reduction in viable bacterial cells. Many of the proteins identified in our screen are predicted to affect peptidoglycan re-modeling, and our results support significant cell wall structural remodeling activity during B. anthracis infection. Identification of L-alanine amidases with B. anthracis specificity may suggest new potential therapeutic targets
A Communal Catalogue Reveals Earth\u27s Multiscale Microbial Diversity
Our growing awareness of the microbial world\u27s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth\u27s microbial diversity
Loss of Metal Ions, Disulfide Reduction and Mutations Related to Familial ALS Promote Formation of Amyloid-Like Aggregates from Superoxide Dismutase
Mutations in the gene encoding Cu-Zn superoxide dismutase (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (FALS). Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1. Therefore, the formation of amyloid fibrils from human SOD1 was investigated. When agitated at acidic pH in the presence of low concentrations of guanidine or acetonitrile, metalated SOD1 formed fibrillar material which bound both thioflavin T and Congo red and had circular dichroism and infrared spectra characteristic of amyloid. While metalated SOD1 did not form amyloid-like aggregates at neutral pH, either removing metals from SOD1 with its intramolecular disulfide bond intact or reducing the intramolecular disulfide bond of metalated SOD1 was sufficient to promote formation of these aggregates. SOD1 formed amyloid-like aggregates both with and without intermolecular disulfide bonds, depending on the incubation conditions, and a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) formed amyloid-like aggregates at neutral pH under reducing conditions. ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Furthermore, the occurrence of amyloid-like aggregates per se does not depend on forming intermolecular disulfide bonds, and multiple forms of such aggregates can be produced from SOD1
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