Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppressor Mutations Linking gpsB with the First Committed Step of Peptidoglycan Biosynthesis in Listeria monocytogenes

ABSTRACT The cell division protein GpsB is a regulator of the penicillin binding protein A1 (PBP A1) in the Gram-positive human pathogen Listeria monocytogenes. Penicillin binding proteins mediate the last two steps of peptidoglycan biosynthesis as they polymerize and cross-link peptidoglycan strands, the main components of the bacterial cell wall. It is not known what other processes are controlled by GpsB. L. monocytogenesgpsB mutants are unable to grow at 42°C, but we observed that spontaneous suppressors correcting this defect arise on agar plates with high frequency. We here describe a first set of gpsB suppressors that mapped to the clpC and murZ genes. While ClpC is the ATPase component of the Clp protease, MurZ is a paralogue of the listerial UDP–N-acetylglucosamine (UDP-GlcNAc) 1-carboxyvinyltransferase MurA. Both enzymes catalyze the enolpyruvyl transfer from phosphoenolpyruvate to UDP-GlcNAc, representing the first committed step of peptidoglycan biosynthesis. We confirmed that clean deletion of the clpC or murZ gene suppressed the ΔgpsB phenotype. It turned out that the absence of either gene leads to accumulation of MurA, and we show that artificial overexpression of MurA alone was sufficient for suppression. Inactivation of other UDP-GlcNAc-consuming pathways also suppressed the heat-sensitive growth of the ΔgpsB mutant, suggesting that an increased influx of precursor molecules into peptidoglycan biosynthesis can compensate for the lack of GpsB. Our results support a model according to which PBP A1 becomes misregulated and thus toxic in the absence of GpsB due to unproductive consumption of cell wall precursor molecules. IMPORTANCE The late cell division protein GpsB is important for cell wall biosynthesis in Gram-positive bacteria. GpsB of the human pathogen L. monocytogenes interacts with one of the key enzymes of this pathway, penicillin binding protein A1 (PBP A1), and influences its activity. PBP A1 catalyzes the last two steps of cell wall biosynthesis, but it is unknown how GpsB controls PBP A1. We observed that a L. monocytogenesgpsB mutant forms spontaneous suppressors and have mapped their mutations to genes mediating and influencing the first step of cell wall biosynthesis, likely stimulating the influx of metabolites into this pathway. We assume that GpsB is important to ensure productive incorporation of cell wall precursors into the peptidoglycan sacculus by PBP A1.
Codon usage and codon pair patterns in non-grass monocot genomes

Background and Aims Studies on codon usage in monocots have focused on grasses, and observed patterns of this taxon were generalized to all monocot species. Here, non-grass monocot species were analysed to investigate the differences between grass and non-grass monocots. Methods First, studies of codon usage in monocots were reviewed. The current information was then extended regarding codon usage, as well as codon-pair context bias, using four completely sequenced non-grass monocot genomes (Musa acuminata, Musa balbisiana, Phoenix dactylifera and Spirodela polyrhiza) for which comparable transcriptome datasets are available. Measurements were taken regarding relative synonymous codon usage, effective number of codons, derived optimal codon and GC content and then the relationships investigated to infer the underlying evolutionary forces. Key Results The research identified optimal codons, rare codons and preferred codon-pair context in the non-grass monocot species studied. In contrast to the bimodal distribution of GC3 (GC content in third codon position) in grasses, non-grass monocots showed a unimodal distribution. Disproportionate use of G and C (and of A and T) in two- and four-codon amino acids detected in the analysis rules out the mutational bias hypothesis as an explanation of genomic variation in GC content. There was found to be a positive relationship between CAI (codon adaptation index; predicts the level of expression of a gene) and GC3. In addition, a strong correlation was observed between coding and genomic GC content and negative correlation of GC3 with gene length, indicating a strong impact of GC-biased gene conversion (gBGC) in shaping codon usage and nucleotide composition in non-grass monocots. Conclusion Optimal codons in these non-grass monocots show a preference for G/C in the third codon position. These results support the concept that codon usage and nucleotide composition in non-grass monocots are mainly driven by gBGC.
IL-18 cleavage triggers cardiac inflammation and fibrosis upon &bgr;-adrenergic insult

Aims Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult. Methods and results Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon β-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1β, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced β1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis. Conclusion Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.
Cyberbullying and self-esteem in Australian adults

Cyberbullying research is currently focused on identifying personal factors which increase the risk of an individual being involved in the behaviour. Recent findings indicate that within the web of cyberbullying culture a large group of individuals are both cyberbullies and victims. This group of cyberbully/victims has been shown to differ from pure cyberbullies or victims on various factors during adolescence; particularly self-esteem. However, little research to date has investigated cyberbullying behaviour in adults. The current study examined the prevalence of cyberbully typologies and their relationship with self-esteem within a convenience sample of 164 Australian young adults (72% being females; 17-25 years). Results found that the largest group identified were cyberbully/victims (62%), followed by individuals not involved (17%), cyberbullies (11%) and cybervictims (10%) respectively. The ratio of males and females in each of the four cyberbully typologies was similar. Contrary to previous research, all four cyberbully typologies reported similar levels of self-esteem. These findings suggest that research should examine cyberbullying behaviour across all age groups to determine if this is related to different factors in adolescence compared to adulthood. Limitations and future recommendations are discussed.
Motivation and Retention of Physicians in Primary Healthcare Facilities: A Qualitative Study from Abbottabad, Pakistan

BACKGROUND Workforce motivation and retention is important for the functionality and quality of service delivery in health systems of developing countries. Despite huge primary healthcare (PHC) infrastructure, Pakistan's health indicators are not impressive; mainly because of under-utilization of facilities and low patient satisfaction. One of the major underlying issues is staff absenteeism. The study aimed to identify factors affecting retention and motivation of doctors working in PHC facilities of Pakistan. METHODS An exploratory study was conducted in a rural district in Khyber Puktunkhwa (KP) province, in Pakistan. A conceptual framework was developed comprising of three organizational, individual, and external environmental factors. Qualitative research methods comprising of semi-structured interviews with doctors working in basic health units (BHUs) and in-depth interviews with district and provincial government health managers were used. Document review of postings, rules of business and policy actions was also conducted. Triangulation of findings was carried out to arrive at the final synthesis. RESULTS Inadequate remuneration, unreasonable facilities at residence, poor work environment, political interference, inadequate supplies and medical facilities contributed to lack of motivation among both male and female doctors. The physicians accepted government jobs in BHUs with a belief that these jobs were more secure, with convenient working hours. Male physicians seemed to be more motivated because they faced less challenges than their female counterparts in BHUs especially during relocations. Overall, the organizational factors emerged as the most significant whereby human resource policy, career growth structure, performance appraisal and monetary benefits played an important role. Gender and marital status of female doctors was regarded as most important individual factor affecting retention and motivation of female doctors in BHUs. CONCLUSION Inadequate remuneration, unreasonable facilities at residence, poor work environment, political interference, inadequate supplies, and medical facilities contributed to lack of motivation in physicians in our study. Our study advocates that by addressing the retention and motivation challenges, service delivery can be made more responsive to the patients and communities in Pakistan and other similar settings.
A Secondary Analysis of Sleep Quality Changes in Older Adults From a Randomized Trial of an MBSR Program

This secondary analysis examined changes in sleep quality associated with participation in a Mindfulness-Based Stress Reduction (MBSR) program among healthy older adults. Data were collected at baseline, 8-weeks post-treatment, and a 6-month follow-up from adults aged ≥ 65 (N = 200), randomly assigned to MBSR or a waitlist control. Group differences were examined using mixed analysis of covariance with repeated measures on the total Pittsburgh Sleep Quality Index (PSQI) score. A small-sized, significant effect was found on overall sleep among MBSR participants with baseline PSQI scores > 5, indicative of a sleep disturbance, F(2, 80) = 4.32, p = . 02, ηp2 = . 05. A medium-sized, significant effect was found for MBSR participants with baseline PSQI scores ≥ 10, F(2, 28) = 3.13, p = . 04, ηp2 = . 10. These findings indicate that improved sleep quality for older adults who have higher levels of sleep disturbance may be associated with participation in MBSR.
Distinct roles for U‐type proteins in iron–sulfur cluster biosynthesis revealed by genetic analysis of the Bacillus subtilis sufCDSUB operon

The biosynthesis of iron–sulfur (Fe–S) clusters in Bacillus subtilis is mediated by the SUF‐like system composed of the sufCDSUB gene products. This system is unique in that it is a chimeric machinery comprising homologues of E. coli SUF components (SufS, SufB, SufC and SufD) and an ISC component (IscU). B. subtilis SufS cysteine desulfurase transfers persulfide sulfur to SufU (the IscU homologue); however, it has remained controversial whether SufU serves as a scaffold for Fe–S cluster assembly, like IscU, or acts as a sulfur shuttle protein, like E. coli SufE. Here we report that reengineering of the isoprenoid biosynthetic pathway in B. subtilis can offset the indispensability of the sufCDSUB operon, allowing the resultant Δsuf mutants to grow without detectable Fe–S proteins. Heterologous bidirectional complementation studies using B. subtilis and E. coli mutants showed that B. subtilis SufSU is interchangeable with E. coli SufSE but not with IscSU. In addition, functional similarity in SufB, SufC and SufD was observed between B. subtilis and E. coli. Our findings thus indicate that B. subtilis SufU is the protein that transfers sulfur from SufS to SufB, and that the SufBCD complex is the site of Fe–S cluster assembly.
Critical behavior within 20 fs drives the out-of-equilibrium laser-induced magnetic phase transition in nickel

High-harmonic spectroscopies reveal that fast energy transfer within 20 fs triggers ultrafast magnetic phase transition in Ni. It has long been known that ferromagnets undergo a phase transition from ferromagnetic to paramagnetic at the Curie temperature, associated with critical phenomena such as a divergence in the heat capacity. A ferromagnet can also be transiently demagnetized by heating it with an ultrafast laser pulse. However, to date, the connection between out-of-equilibrium and equilibrium phase transitions, or how fast the out-of-equilibrium phase transitions can proceed, was not known. By combining time- and angle-resolved photoemission with time-resolved transverse magneto-optical Kerr spectroscopies, we show that the same critical behavior also governs the ultrafast magnetic phase transition in nickel. This is evidenced by several observations. First, we observe a divergence of the transient heat capacity of the electron spin system preceding material demagnetization. Second, when the electron temperature is transiently driven above the Curie temperature, we observe an extremely rapid change in the material response: The spin system absorbs sufficient energy within the first 20 fs to subsequently proceed through the phase transition, whereas demagnetization and the collapse of the exchange splitting occur on much longer, fluence-independent time scales of ~176 fs. Third, we find that the transient electron temperature alone dictates the magnetic response. Our results are important because they connect the out-of-equilibrium material behavior to the strongly coupled equilibrium behavior and uncover a new time scale in the process of ultrafast demagnetization.
Utilization of health care services by migrants in Europe—a systematic literature review

Introduction Our study reviewed the empirical evidence on the utilization of health care services by migrants in Europe, and on differences in health service utilization between migrants and non-migrants across European countries. Sources of data A systematic literature review was performed, searching the databases Medline, Cinahl and Embase and covering the period from January 2009 to April 2016. The final number of articles included was 39. Areas of agreement Utilization of accident and emergency services and hospitalizations were higher among migrants compared with non-migrants in most countries for which evidence was available. In contrast, screening and outpatient visits for specialized care were generally used less often by migrants. Areas of controversy Utilization of general practitioner services among migrants compared with non-migrants presents a diverging picture. Growing points Compared with previous systematic reviews, the results indicate a clearer picture of the differences in health service utilization between migrants and non-migrants in Europe. Areas timely for developing research A comprehensive comparison across European countries is impossible because the number of studies is still limited. Further research should also help to identify barriers regarding the utilization of health care services by migrants.
Clinicopathological Features of Bone Marrow Infiltration in Hodgkin Lymphoma. Should Bone Marrow Staging Be Done Only in High Risk Patients?

OBJECTIVE The frequency of bone marrow infiltration by Hodgkin lymphoma is low and varies from 3 to 18%. Hence there exists a dilemma whether bone marrow staging should be done only in the high risk cases. This study aims to study the clinicopathological features and the histomorphology of bone marrow infiltration by Hodgkin Lymphoma. MATERIAL AND METHOD Bone marrow aspirates and biopsies from cases of Hodgkin lymphoma diagnosed between 2007 and 2015 were studied. Immunohistochemistry with CD15 and CD30 were done in necessary cases. Bone marrow infiltration was correlated with various clinicopathological parameters. RESULTS Ten of the 81 cases (12.3%) studied showed infiltration by Hodgkin lymphoma in the bone marrow biopsy sections. All the aspirates were negative. Bone marrow in the involved cases showed Reed-Sternberg cells and/or mononuclear Hodgkin cells positive for CD30 in a polymorphous inflammatory background. Cases of lymphocyte depleted subtype (66%) and those with leucopenia/ thrombocytopenia (100%) were frequently associated with bone marrow infiltration. B-symptoms, anemia and mixed cellularity were the other risk factors. However none of these risk factors were noted in two out of the ten cases with bone marrow infiltration. CONCLUSION As the role of bone marrow aspirate is minimal in the staging of Hodgkin lymphoma, bone marrow biopsy should be the method of choice. Immunohistochemistry helps in the doubtful cases. Bone marrow involvement was frequent but not confined to the high risk groups. Our findings suggest that bone marrow staging should not be restricted to the high risk cases alone.
Long-term effects of Class II Herbst treatment on the pharyngeal airway width

Objective The aim was to assess the long-term effects of Class II malocclusion treatment with the Herbst appliance on the pharyngeal airway (PA) width in comparison to untreated individuals with Classes I and II malocclusion. Methods Lateral cephalometric radiographs of 13 male Class II patients from before (T1) and after (T2) treatment with the Herbst appliance as well as after the end of growth (T3) were retrospectively analyzed and compared to two untreated age- and gender-matched samples with Class I (n = 13) or Class II (n = 13) malocclusion. The PA dimensions were measured using the parameters p (narrowest distance between the soft palate and the posterior pharyngeal wall) and t (narrowest distance between the base of the tongue and the posterior pharyngeal wall). In addition, standard cephalometric measurements were performed. Results Relevant changes in PA dimensions were only seen for the post-treatment period, during which the distances p and t showed a significant increase in the Herbst group only (∆p: 2.3 mm, ∆t: 3.3 mm) while remaining similar in both untreated groups (∆p: 0.5 mm, ∆t: 0.5 mm, respectively, ∆p: 0.7 mm, ∆t: 1.6 mm). During the same period, posterior face height showed a significantly larger increase in the Herbst group than in both control groups (8.2 versus 5.8 mm, respectively, 5.4 mm), whereas anterior face height (NL-Me) showed a similar development in all groups (4.6 versus 4.4 mm, respectively 3.2 mm). Conclusion In the long term, Herbst treatment resulted in a significant post-treatment increase of PA width, possibly due to an increased lower posterior facial height development compared to untreated individuals.
Potential Relationship between Passive Plantar Flexor Stiffness and Running Performance

Abstract The present study aimed to determine the relationship between passive stiffness of the plantar flexors and running performance in endurance runners. Forty-eight well-trained male endurance runners and 24 untrained male control subjects participated in this study. Plantar flexor stiffness during passive dorsiflexion was calculated from the slope of the linear portion of the torque-angle curve. Of the endurance runners included in the present study, running economy in 28 endurance runners was evaluated by measuring energy cost during three 4-min trials (14, 16, and 18 km/h) of submaximal treadmill running. Passive stiffness of the plantar flexors was significantly higher in endurance runners than in untrained subjects. Moreover, passive plantar flexor stiffness in endurance runners was significantly correlated with a personal best 5000-m race time. Furthermore, passive plantar flexor stiffness in endurance runners was significantly correlated with energy cost during submaximal running at 16 km/h and 18 km/h, and a trend towards such significance was observed at 14 km/h. The present findings suggest that stiffer plantar flexors may help achieve better running performance, with greater running economy, in endurance runners. Therefore, in the clinical setting, passive stiffness of the plantar flexors may be a potential parameter for assessing running performance.
Iron Deficiency Anemia, Not Iron Deficiency, Is Associated with Reduced Attention in Healthy Young Women

Women of reproductive age are at increased risk for iron deficiency (ID) and iron deficiency anemia (IDA), with both implicated in decreased cognitive function (CF). Obesity may complicate this association via inflammatory-mediated ferritin elevation. This cross-sectional study examined the association between hematological iron status (iron replete (IR), ID or IDA) and CF in healthy, young (18–35 years) women of normal-weight (NW: BMI 18.5– 24.9 kg/m2) or obese-weight (OB: BMI >30 kg/m2). Participants completed a validated, computer-based cognition assessment evaluating impulsivity, attention, information processing, memory and executive function; CF reported as z-scores (mean ± SD). Iron status and CF were compared between groups via ANOVA, with adjustment for potential confounders (BMI, physical activity, C-reactive protein) via ANCOVA. A total of 157 NW and 142 OB women (25.8 ± 5.1 years) participated. Prevalence of ID and IDA were 14% and 6% respectively, with no significant difference between NW and OB groups. Women with IDA scored significantly lower on attention (although within normal range; ±1 z-score), compared to ID (IDA: −0.75 ± 1.89; ID: 0.53 ± 1.37; p = 0.004) but not IR (0.03 ± 1.33, p = 0.21) groups; there were no significant differences between ID and IR groups (p = 0.34). Adjustment for confounders did not significantly alter these results. In conclusion, women with IDA showed significantly reduced attention compared to women with ID.
Sharp-rejection highpass and dual-band bandpass planar filters with multi-transmission-zero-generation transversal cell

A method to produce multiple transmission zeros (TZs) is applied to design sharp-rejection planar highpass filters (HPFs) and dual-passband filters (BPFs). It consists of adding an external transversal cell to a basic filter to create TZs in its response without damaging its in-band amplitude and group-delay variation. Thus, contrary to other filter design techniques, in-band requisites and stopband TZ creation can be separately addressed in the entire filter synthesis process. Such technique could have great potential in other technologies, such as waveguide filters for satellite communications, in which low in-band group-delay variation and adjustable high selectivity are necessary. Measurements for a microstrip HPF and simulations for a stripline dual-band BPF are shown.