ResearchPad - techniques https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Estimating the potential impact of behavioral public health interventions nationally while maintaining agreement with global patterns on relative risks]]> https://www.researchpad.co/article/elastic_article_13880 This paper introduces a novel method to evaluate the local impact of behavioral scenarios on disease prevalence and burden with representative individual level data while ensuring that the model is in agreement with the qualitative patterns of global relative risk (RR) estimates. The method is used to estimate the impact of behavioral scenarios on the burden of disease due to ischemic heart disease (IHD) and diabetes in the Turkish adult population.MethodsDisease specific Hierarchical Bayes (HB) models estimate the individual disease probability as a function of behaviors, demographics, socio-economics and other controls, where constraints are specified based on the global RR estimates. The simulator combines the counterfactual disease probability estimates with disability adjusted life year (DALY)-per-prevalent-case estimates and rolls up to the targeted population level, thus reflecting the local joint distribution of exposures. The Global Burden of Disease (GBD) 2016 study meta-analysis results guide the analysis of the Turkish National Health Surveys (2008 to 2016) that contain more than 90 thousand observations.FindingsThe proposed Qualitative Informative HB models do not sacrifice predictive accuracy versus benchmarks (logistic regression and HB models with non-informative and numerical informative priors) while agreeing with the global patterns. In the Turkish adult population, Increasing Physical Activity reduces the DALYs substantially for both IHD by 8.6% (6.4% 11.2%), and Diabetes by 8.1% (5.8% 10.6%), (90% uncertainty intervals). Eliminating Smoking and Second-hand Smoke predominantly decreases the IHD burden 13.1% (10.4% 15.8%) versus Diabetes 2.8% (1.1% 4.6%). Increasing Fruit and Vegetable Consumption, on the other hand, reduces IHD DALYs by 4.1% (2.8% 5.4%) while not improving the Diabetes burden 0.1% (0% 0.1%).ConclusionWhile the national RR estimates are in qualitative agreement with the global patterns, the scenario impact estimates are markedly different than the attributable risk estimates from the GBD analysis and allow evaluation of practical scenarios with multiple behaviors. ]]> <![CDATA[Ultrasound prediction of Zika virus-associated congenital injury using the profile of fetal growth]]> https://www.researchpad.co/article/elastic_article_13878 Zika virus (ZIKV) is a mosquito-transmitted flavivirus, recently linked to microcephaly and central nervous system anomalies following infection in pregnancy. Striking findings of disproportionate growth with a smaller than expected head relative to body length have been observed more commonly among fetuses with exposure to ZIKV in utero compared to pregnancies without ZIKV infection regardless of other signs of congenital infection including microcephaly. This study’s objective was to determine the diagnostic accuracy of femur-sparing profile of intrauterine growth restriction for the identification of ZIKV-associated congenital injuries on postnatal testing. A retrospective cohort study of pregnant women with possible or confirmed ZIKV infection between January 1, 2016 and December 31, 2017 were included. Subjects were excluded if no prenatal ultrasound was available. A femur-sparing profile of growth restriction determined using INTERGROWTH-21st sonographic standard for head circumference to femur length (HC: FL). Congenital injuries were determined postnatally by imaging, comprehensive eye exam and standard newborn hearing screen. A total of 111 pregnant women diagnosed with ZIKV infection underwent fetal ultrasound and 95 neonates had complete postnatal evaluation. Prenatal microcephaly was detected in 5% of fetuses (6/111). Postnatal testing detected ZIKV-associated congenital injuries in 25% of neonates (24/95). A HC: FL Z-score ≤ -1.3 had a 52% specificity (95% CI 41–63%), 82% negative predictive value (NPV, 95% CI 73–88%) for the detection of ZIKV-associated congenital injuries in the neonatal period. A more stringent threshold with a Z-score ≤ -2 was associated with a 90% specificity (95% CI 81–95%), 81% NPV (95% CI 77–85%). Excluding cases of fetal microcephaly, HC: FL (Z-score ≤ -2) demonstrated a similar specificity (89%, 95% CI 81–95%) with superior NPV (87%, 95% CI 84–90%). The sonographic recognition of a normally proportioned fetus may be useful prenatally to exclude a wider spectrum of ZIKV-associated congenital injuries detected postnatally.

]]>
<![CDATA[<i>In silico</i> analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors]]> https://www.researchpad.co/article/elastic_article_13870 Long non-coding RNAs (lncRNAs) are characterized as having 200 nucleotides or more and not coding any protein, and several been identified as differentially expressed in several human malignancies, including breast cancer.MethodsHere, we evaluated lncRNAs differentially expressed in triple-negative breast cancer (TNBC) from a cDNA microarray data set obtained in a previous study from our group. Using in silico analyses in combination with a review of the current literature, we identify three lncRNAs as potential prognostic factors for TNBC patients.ResultsWe found that the expression of WDFY3-AS2, BDNF-AS, and AFAP1-AS1 was associated with poor survival in patients with TNBCs. WDFY3-AS2 and BDNF-AS are lncRNAs known to play an important role in tumor suppression of different types of cancer, while AFAP1-AS1 exerts oncogenic activity.ConclusionOur findings provided evidence that WDFY3-AS2, BDNF-AS, and AFAP1-AS1 may be potential prognostic factors in TNBC development. ]]> <![CDATA[Low LEF1 expression is a biomarker of early T-cell precursor, an aggressive subtype of T-cell lymphoblastic leukemia]]> https://www.researchpad.co/article/elastic_article_13868 Early T-cell precursor (ETP) is the only subtype of acute T-cell lymphoblastic leukemia (T-ALL) listed in the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Patients with ETP tend to have worse disease outcomes. ETP is defined by a series of immune markers. The diagnosis of ETP status can be vague due to the limitation of the current measurement. In this study, we performed unsupervised clustering and supervised prediction to investigate whether a molecular biomarker can be used to identify the ETP status in order to stratify risk groups. We found that the ETP status can be predicted by the expression level of Lymphoid enhancer binding factor 1 (LEF1) with high accuracy (AUC of ROC = 0.957 and 0.933 in two T-ALL cohorts). The patients with ETP subtype have a lower level of LEF1 comparing to the those without ETP. We suggest that incorporating the biomarker LEF1 with traditional immune-phenotyping will improve the diagnosis of ETP.

]]>
<![CDATA[Crystal structure of <i>Thermus thermophilus</i> methylenetetrahydrofolate dehydrogenase and determinants of thermostability]]> https://www.researchpad.co/article/elastic_article_13865 The elucidation of mechanisms behind the thermostability of proteins is extremely important both from the theoretical and applied perspective. Here we report the crystal structure of methylenetetrahydrofolate dehydrogenase (MTHFD) from Thermus thermophilus HB8, a thermophilic model organism. Molecular dynamics trajectory analysis of this protein at different temperatures (303 K, 333 K and 363 K) was compared with homologous proteins from the less temperature resistant organism Thermoplasma acidophilum and the mesophilic organism Acinetobacter baumannii using several data reduction techniques like principal component analysis (PCA), residue interaction network (RIN) analysis and rotamer analysis. These methods enabled the determination of important residues for the thermostability of this enzyme. The description of rotamer distributions by Gini coefficients and Kullback–Leibler (KL) divergence both revealed significant correlations with temperature. The emerging view seems to indicate that a static salt bridge/charged residue network plays a fundamental role in the temperature resistance of Thermus thermophilus MTHFD by enhancing both electrostatic interactions and entropic energy dispersion. Furthermore, this analysis uncovered a relationship between residue mutations and evolutionary pressure acting on thermophilic organisms and thus could be of use for the design of future thermostable enzymes.

]]>
<![CDATA[TIM, a targeted insertional mutagenesis method utilizing CRISPR/Cas9 in <i>Chlamydomonas reinhardtii</i>]]> https://www.researchpad.co/article/elastic_article_13864 Generation and subsequent analysis of mutants is critical to understanding the functions of genes and proteins. Here we describe TIM, an efficient, cost-effective, CRISPR-based targeted insertional mutagenesis method for the model organism Chlamydomonas reinhardtii. TIM utilizes delivery into the cell of a Cas9-guide RNA (gRNA) ribonucleoprotein (RNP) together with exogenous double-stranded (donor) DNA. The donor DNA contains gene-specific homology arms and an integral antibiotic-resistance gene that inserts at the double-stranded break generated by Cas9. After optimizing multiple parameters of this method, we were able to generate mutants for six out of six different genes in two different cell-walled strains with mutation efficiencies ranging from 40% to 95%. Furthermore, these high efficiencies allowed simultaneous targeting of two separate genes in a single experiment. TIM is flexible with regard to many parameters and can be carried out using either electroporation or the glass-bead method for delivery of the RNP and donor DNA. TIM achieves a far higher mutation rate than any previously reported for CRISPR-based methods in C. reinhardtii and promises to be effective for many, if not all, non-essential nuclear genes.

]]>
<![CDATA[Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish]]> https://www.researchpad.co/article/elastic_article_13853 Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.

]]>
<![CDATA[Fruit and vegetable consumption in Europe according to gender, educational attainment and regional affiliation—A cross-sectional study in 21 European countries]]> https://www.researchpad.co/article/elastic_article_13846 The purpose of the present study was to examine fruit and vegetable consumption according to gender, educational attainment and regional affiliation in Europe.DesignCross-sectional study.Setting21 European countries.Participants37 672 adults participating in the 7th round of the European Social Survey.Main outcome measuresFruit and vegetable consumption was measured using two single frequency questions. Responses were dichotomized into low (<once a day) and high (≥once a day) consumption. The association between consumption of fruit and vegetables and gender, educational level, regional affiliation was examined using logistic regression analyses.ResultsOverall, females showed increased odds of consuming fruit (OR 1.71 (95%CI:1.62, 1.79) and vegetable (1.59 (1.51, 1.67)) compared to males and high educated participants showed increased odds of consuming fruit (1.53 (1.43, 1.63)) and vegetables (1.86 (1.74, 2.00)) compared to low educated participants. Our results also showed that participants living in Eastern Europe had the lowest odds of consuming fruit and vegetables, whereas participants from Southern- and Northern Europe had the highest odds of consuming fruit and vegetables, respectively. Results from interaction analyses confirmed the positive association between fruit and vegetable consumption and educational level, although for some European regions, decreased odds of fruit and vegetables was observed among medium educated participants compared to those with low education.ConclusionsOverall, the present study showed that being female and having a high education were associated with increased consumption of fruit and vegetables. However, the direction and strength of these relationships depends on regional affiliations. ]]> <![CDATA[Fine-scale visualizing the hierarchical structure of mouse biliary tree with fluorescence microscopy method]]> https://www.researchpad.co/article/elastic_article_13843 The liver is a vital organ and the hepatic lobule serves as the most basic structural and functional unit which is mainly assembled with parenchymal cells including hepatocytes and biliary epithelial cells. The continuous tubular arrangement of biliary cells which constitutes the biliary tracts is critical for liver function, however, the biliary tracts are often disrupted in many liver diseases such as cirrhosis and some congenital disorders. Visualization of the biliary tracts in fine-scale and three-dimension will help to understanding the structure basis of these liver diseases. In the present study, we established several biliary tract injury mouse models by diet feeding, surgery or genetic modification. The cytoplasm and nuclei of the parenchymal cells were marked by active uptake of fluorescent dyes Rhodamine B (red) and Hoechst (blue), respectively. After the removal of liver en bloc, the biliary tracts were retrogradely perfused with green fluorescent dye, fluorescein isothiocyanate (FITC). The liver was then observed under confocal microscopy. The fine-scale and three-dimensional (3D) structure of the whole biliary tree, particularly the network of the end-terminal bile canaliculi and neighboring hepatocytes were clearly visualized. The biliary tracts displayed clear distinct characteristics in normal liver and diseased liver models. Taken together, we have developed a simple and repeatable imaging method to visualize the fine-scale and hierarchical architecture of the biliary tracts spreading in the mouse liver.

]]>
<![CDATA[Quantitative live imaging of Venus::BMAL1 in a mouse model reveals complex dynamics of the master circadian clock regulator]]> https://www.researchpad.co/article/elastic_article_13838 Cell-autonomous circadian clocks are transcriptional/translational feedback loops that co-ordinate almost all mammalian physiology and behaviour. Although their genetic basis is well understood, we are largely ignorant of the natural behaviour of clock proteins and how they work within these loops. This is particularly true for the essential transcriptional activator BMAL1. To address this, we created and validated a mouse carrying a fully functional knock-in allele that encodes a fluorescent fusion of BMAL1 (Venus::BMAL1). Quantitative live imaging in tissue explants and cells, including the central clock of the suprachiasmatic nucleus (SCN), revealed the circadian expression, nuclear-cytoplasmic mobility, fast kinetics and surprisingly low molecular abundance of endogenous BMAL1, providing significant quantitative insights into the intracellular mechanisms of circadian timing at single-cell resolution.

]]>
<![CDATA[Inferring a simple mechanism for alpha-blocking by fitting a neural population model to EEG spectra]]> https://www.researchpad.co/article/elastic_article_13836 One of the most striking features of the human electroencephalogram (EEG) is the presence of neural oscillations in the range of 8-13 Hz. It is well known that attenuation of these alpha oscillations, a process known as alpha blocking, arises from opening of the eyes, though the cause has remained obscure. In this study we infer the mechanism underlying alpha blocking by fitting a neural population model to EEG spectra from 82 different individuals. Although such models have long held the promise of being able to relate macroscopic recordings of brain activity to microscopic neural parameters, their utility has been limited by the difficulty of inferring these parameters from fits to data. Our approach involves fitting eyes-open and eyes-closed EEG spectra in a way that minimizes unnecessary differences in model parameters between the two states. Surprisingly, we find that changes in just one parameter, the level of external input to the inhibitory neurons in cortex, is sufficient to explain the attenuation of alpha oscillations. This indicates that opening of the eyes reduces alpha activity simply by increasing external inputs to the inhibitory neurons in the cortex.

]]>
<![CDATA[Host interactors of effector proteins of the lettuce downy mildew <i>Bremia lactucae</i> obtained by yeast two-hybrid screening]]> https://www.researchpad.co/article/elastic_article_13834 Plant pathogenic bacteria, fungi and oomycetes secrete effector proteins to manipulate host cell processes to establish a successful infection. Over the last decade the genomes and transcriptomes of many agriculturally important plant pathogens have been sequenced and vast candidate effector repertoires were identified using bioinformatic analyses. Elucidating the contribution of individual effectors to pathogenicity is the next major hurdle. To advance our understanding of the molecular mechanisms underlying lettuce susceptibility to the downy mildew Bremia lactucae, we mapped physical interactions between B. lactucae effectors and lettuce candidate target proteins. Using a lettuce cDNA library-based yeast-two-hybrid system, 61 protein-protein interactions were identified, involving 21 B. lactucae effectors and 46 unique lettuce proteins. The top ten interactors based on the number of independent colonies identified in the Y2H and two interactors that belong to gene families involved in plant immunity, were further characterized. We determined the subcellular localization of the fluorescently tagged lettuce proteins and their interacting effectors. Importantly, relocalization of effectors or their interactors to the nucleus was observed for four protein-pairs upon their co-expression, supporting their interaction in planta.

]]>
<![CDATA[Insight into the protein solubility driving forces with neural attention]]> https://www.researchpad.co/article/elastic_article_13832 The solubility of proteins is a crucial biophysical aspect when it comes to understanding many human diseases and to improve the industrial processes for protein production. Due to its relevance, computational methods have been devised in order to study and possibly optimize the solubility of proteins. In this work we apply a deep-learning technique, called neural attention to predict protein solubility while “opening” the model itself to interpretability, even though Machine Learning models are usually considered black boxes. Thank to the attention mechanism, we show that i) our model implicitly learns complex patterns related to emergent, protein folding-related, aspects such as to recognize β-amyloidosis regions and that ii) the N-and C-termini are the regions with the highes signal fro solubility prediction. When it comes to enhancing the solubility of proteins, we, for the first time, propose to investigate the synergistic effects of tandem mutations instead of “single” mutations, suggesting that this could minimize the number of required proposed mutations.

]]>
<![CDATA[Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>]]> https://www.researchpad.co/article/elastic_article_13829 Clonorchiasis, closely related to cholangiocarcinoma and hepatocellular carcinoma, has led to a negative socioeconomic impact in global areas especially some Asian endemic regions. Owing to the emergence of drug resistance and hypersensitivity reactions after the massive and repeated use of praziquantel as well as the lack of effective vaccines, searching for new strategies that prevent and treat clonorchiasis has become an urgent matter. Clonorchis sinensis, the causative agent of clonorchiasis, long-term inhabits the microaerobic and limited-glucose environment of the bile ducts. Adequate nutrients are essential for adult flukes to resist the adverse condition and survive in the crowed habitat. Studies on energy metabolism of adult flukes are beneficial for further exploring host-parasite interactions and developing novel anti-parasitic drugs. Our results suggest that gluconeogenesis probably plays a vital role in energy metabolism of Clonorchis sinensis and exogenous amino acids might be an essential energy source for adult flukes to successfully survive in the host. Our foundational study opens a new avenue for explaining energy metabolism of Clonorchis sinensis and provides a valuable strategy that the gluconeogenesis pathway will be a potential and novel target for the prevention and treatment of clonorchiasis.

]]>
<![CDATA[Murine gammaherpesvirus infection is skewed toward Igλ+ B cells expressing a specific heavy chain V-segment]]> https://www.researchpad.co/article/elastic_article_13826 Murine gammaherpesvirus 68 is a rodent pathogen that is closely related to the human gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated virus. All know gammaherpesviruses are associated with the development of lymphomas, as well as other cancers, in a small subset of infected individuals–particularly those with underlying defects in their immune system (i.e., transplant recipients and HIV infected patients). Because there are very limited small animal models for the human gammaherpesviruses, studies on murine gammaherepsviruses 68 can provide important insights into critical aspects of gammaherpesvirus infections and the association of these viruses with disease development. Another feature of all gammaherpesviruses is their ability to establish a chronic infection of their host–where the virus is maintained for the lifetime of the infected individual. The major target cell harboring chronic gammaherepsvirus infection are B lymphocytes–the cells in the immune system that produce antibodies in response to infections. Here we provide a detailed characterization of the populations of B lymphocytes that become infected by murine gammaherpesvirus 68. This has led to the identification of a specific population of B lymphocytes that is preferentially infected by the virus. This supports a model in which murine gammaherpesvirus infection of B lymphocytes is not random. However, it remains unclear why the virus targets this specific population of B cells for infection.

]]>
<![CDATA[Retrospectively ECG-gated helical vs. non-ECG-synchronized high-pitch CTA of the aortic root for TAVI planning]]> https://www.researchpad.co/article/elastic_article_13825 Multidetector computed tomography (MDCT) plays a key role in patient assessment prior to transcatheter aortic valve implantation (TAVI). However, to date no consensus has been established on what is the optimal pre-procedural imaging protocol. Variability in pre-TAVI acquisition protocols may lead to discrepancies in aortic annulus measurements and may potentially influence prosthesis size selection.PurposeThe current study evaluates the magnitude of differences in aortic annulus measurements using max-systolic, end-diastolic, and non-ECG-synchronized imaging, as well as the impact of method on prosthesis size selection.Material and methodsFifty consecutive TAVI-candidates, who underwent retrospectively-ECG-gated CT angiography (CTA) of the aortic root, directly followed by non-ECG-synchronized high-pitch CT of the entire aorta, were retrospectively included. Aortic root dimensions were assessed at each 10% increment of the R-R interval (0–100%) and on the non-ECG-synchronized scan. Dimensional changes within the cardiac cycle were evaluated using a 1-way repeated ANOVA. Agreement in measurements between max-systole, end-diastole and non-ECG-synchronized scans was assessed with Bland-Altman analysis.ResultsMaximal dimensions of the aortic root structures and minimum annulus-coronary ostia distances were measured during systole. Max-systolic measurements were significantly and substantially larger than end-diastolic (p<0.001) and non-ECG-synchronized measurements (p<0.001). Due to these discrepancies, the three methods resulted in the same prosthesis size selection in only 48–62% of patients.ConclusionsThe systematic differences between max-systolic, end-diastolic and non-ECG-synchronized measurements for relevant aortic annular dimensions are both statistically significant and clinically relevant. Imaging strategy impacts prosthesis size selection in nearly half the TAVI-candidates. End-diastolic and non-ECG-synchronized imaging does not provide optimal information for prosthesis size selection. Systolic image acquisition is necessary for assessment of maximal annular dimensions and minimum annulus-coronary ostia distances. ]]> <![CDATA[Relationship between maximal incremental and high-intensity interval exercise performance in elite athletes]]> https://www.researchpad.co/article/elastic_article_13822 This descriptive study aimed to explore the physiological factors that determine tolerance to exertion during high-intensity interval effort. Forty-seven young women (15–28 years old) were enrolled: 23 athletes from Taiwan national or national reserve teams and 24 moderately active females. Each participant underwent a maximal incremental INC (modified Bruce protocol) cardiopulmonary exercise test on the first day and high-intensity interval testing (HIIT) on the second day, both performed on a treadmill. The HIIT protocol involved alternation between 1-min effort at 120% of the maximal speed, at the same slope reached at the end of the INC, and 1-min rest until volitional exhaustion. Gas exchange, heart rate (HR), and muscle oxygenation at the right vastus lateralis, measured by near-infrared spectroscopy, were continuously recorded. The number of repetitions completed (Rlim) by each participant was considered the HIIT tolerance index. The results showed a large difference in the Rlim (range, 2.6–12.0 repetitions) among the participants. Stepwise linear regression revealed that the variance in the Rlim within the cohort was related to the recovery rates of oxygen consumption (V˙O2), HR at the second minute after INC, and muscle tissue saturation index at exhaustion (R = 0.644). In addition, age was linearly correlated with Rlim (adjusted R = −0.518, p < 0.0001). In conclusion, the recovery rates for V˙O2 and HR after the incremental test, and muscle saturation index at exhaustion, were the major physiological factors related to HIIT performance. These findings provide insights into the role of the recovery phase after maximal INC exercise testing. Future research investigating a combination of INC and HIIT testing to determine training-induced performance improvement is warranted.

]]>
<![CDATA[Functional magnetic resonance imaging of the trail-making test in older adults]]> https://www.researchpad.co/article/elastic_article_13819 The trail-making test (TMT) is a popular neuropsychological test, which is used extensively to measure cognitive impairment associated with neurodegenerative disorders in older adults. Behavioural performance on the TMT has been investigated in older populations, but there is limited research on task-related brain activity in older adults. The current study administered a naturalistic version of the TMT to a healthy older-aged population in an MRI environment using a novel, MRI-compatible tablet. Functional MRI was conducted during task completion, allowing characterization of the brain activity associated with the TMT. Performance on the TMT was evaluated using number of errors and seconds per completion of each link. Results are reported for 36 cognitively healthy older adults between the ages of 52 and 85. Task-related activation was observed in extensive regions of the bilateral frontal, parietal, temporal and occipital lobes as well as key motor areas. Increased age was associated with reduced brain activity and worse task performance. Specifically, older age was correlated with decreased task-related activity in the bilateral occipital, temporal and parietal lobes. These results suggest that healthy older aging significantly affects brain function during the TMT, which consequently may result in performance decrements. The current study reveals the brain activation patterns underlying TMT performance in a healthy older aging population, which functions as an important, clinically-relevant control to compare to pathological aging in future investigations.

]]>
<![CDATA[SNP markers for low molecular glutenin subunits (LMW-GSs) at the <i>Glu-A3</i> and <i>Glu-B3</i> loci in bread wheat]]> https://www.researchpad.co/article/elastic_article_13817 The content and composition of seed storage proteins is largely responsible for wheat end-use quality. They mainly consist of polymeric glutenins and monomeric gliadins. According to their electrophoretic mobility, gliadins and glutenins are subdivided into several fractions. Glutenins are classified as high molecular weight or low molecular weight glutenin subunits (HMW-GSs and LMW-GSs, respectively). LMW-GSs are encoded by multigene families located at the orthologous Glu-3 loci. We designed a set of 16 single-nucleotide polymorphism (SNP) markers that are able to detect SDS-PAGE alleles at the Glu-A3 and Glu-B3 loci. The SNP markers captured the diversity of alleles in 88 international reference lines and 27 Mexican cultivars, when compared to SDS-PAGE and STS markers, however, showed a slightly larger percent of multiple alleles, mainly for Glu-B3. SNP markers were then used to determine the Glu-1 and Glu-3 allele composition in 54 CIMMYT historical lines and demonstrated to be useful tool for breeding programs to improve wheat end product properties.

]]>
<![CDATA[The early experiences of Physician Associate students in the UK: A regional cross-sectional study investigating factors associated with engagement]]> https://www.researchpad.co/article/elastic_article_13815 The number of physician associates (PAs) training and working in the UK has increased over the last few years following the proliferation of postgraduate courses. Understanding early experiences and what impacts on engagement is important if we are to appropriately support this relatively new professional group.MethodsThis paper reports on a cross-sectional analysis of the first year of data from a prospective 10-year longitudinal cohort study. First year PA students (n = 89) were enrolled from five universities in one UK region where the training programmes were less than 2 years old. Data collected were: demographic information, wellbeing, burnout and engagement, expectations, placement experience, performance and caring responsibilities. Pearson’s correlations were used to examine relationships between variables and to select variables for a hierarchical regression analysis to understand which factors were associated with engagement. Descriptive statistics were calculated for questions relating to experience.ResultsThe experiences of PA students during their first 3–6 months were mixed. For example, 78.7% of students felt that there were staff on placement they could go to for support, however, 44.8% reported that staff did not know about the role and 61.3% reported that staff did not know what clinical work they should undertake. Regression analysis found that their level of engagement was associated with their perceived career satisfaction, overall well-being, and caring responsibilities.ConclusionsThe support systems required for PAs may need to be examined as results showed that the PA student demographic is different to that of medical students and caring responsibilities are highly associated with engagement. A lack of understanding around the PA role in clinical settings may also need to be addressed in order to better support and develop this workforce. ]]>