Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct roles of DNA polymerases delta and epsilon at the replication fork in Xenopus egg extracts

DNA polymerases δ and ɛ (Polδ and Polɛ) are widely thought to be the major DNA polymerases that function in elongation during DNA replication in eukaryotic cells. However, the precise roles of these polymerases are still unclear. Here we comparatively analysed DNA replication in Xenopus egg extracts in which Polδ or Polɛ was immunodepleted. Depletion of either polymerase resulted in a significant decrease in DNA synthesis and accumulation of short nascent DNA products, indicating an elongation defect. Moreover, Polδ depletion caused a more severe defect in elongation, as shown by sustained accumulation of both short nascent DNA products and single‐stranded DNA gaps, and also by elevated chromatin binding of replication proteins that function more frequently during lagging strand synthesis. Therefore, our data strongly suggest the possibilities that Polδ is essential for lagging strand synthesis and that this function of Polδ cannot be substituted for by Polɛ.
Evidence from Bone Growth that Most of the Infants Dying in the Neonatal Period had been 111 Before Birth

A survey of the pattern of growth, as revealed by the structure of the costo‐chondral junction, suggests that the great majority of infants dying in the neonatal period had intrauterine disease antedating labour. This involves approximately 60% of premature birth deaths and around 75 % of perinatal deaths at term.
Investigating the Relationship Between Attention and Working Memory in Clinical and Community Samples

The first aim of the present study was to investigate whether differences in core deficits in ADHD subtypes lead to dissociable working memory profiles. The second aim was to compare the working memory profiles of inattentive students with those identified as having poor working memory, as they exhibit very similar behavioral profiles. Finally, the relationship between working memory and academic attainment in these groups were also of interest. Four groups of 9-year-olds were recruited: a community sample of children with inattentive symptoms, a clinically diagnosed group of children with ADHD-Combined, children with low working memory, and a healthy comparison group. They were assessed on measures of working memory, IQ, academic attainment, and sustained attention. The findings indicated that the combined and inattentive subtypes could not be distinguished on the basis of their working memory profile. In contrast, those with inattentive symptoms did better on the short-term memory tasks than the low working memory group. The majority of all three atypical groups performed very poorly in reading and math. This pattern can be interpreted as reflecting the link between working memory and academic attainment, even in those with attention problems.
Overcoming sequence misalignments with weighted structural superposition

An appropriate structural superposition identifies similarities and differences between homologous proteins that are not evident from sequence alignments alone. We have coupled our Gaussian‐weighted RMSD (wRMSD) tool with a sequence aligner and seed extension (SE) algorithm to create a robust technique for overlaying structures and aligning sequences of homologous proteins (HwRMSD). HwRMSD overcomes errors in the initial sequence alignment that would normally propagate into a standard RMSD overlay. SE can generate a corrected sequence alignment from the improved structural superposition obtained by wRMSD. HwRMSD's robust performance and its superiority over standard RMSD are demonstrated over a range of homologous proteins. Its better overlay results in corrected sequence alignments with good agreement to HOMSTRAD. Finally, HwRMSD is compared to established structural alignment methods: FATCAT, secondary‐structure matching, combinatorial extension, and Dalilite. Most methods are comparable at placing residue pairs within 2 Å, but HwRMSD places many more residue pairs within 1 Å, providing a clear advantage. Such high accuracy is essential in drug design, where small distances can have a large impact on computational predictions. This level of accuracy is also needed to correct sequence alignments in an automated fashion, especially for omics‐scale analysis. HwRMSD can align homologs with low‐sequence identity and large conformational differences, cases where both sequence‐based and structural‐based methods may fail. The HwRMSD pipeline overcomes the dependency of structural overlays on initial sequence pairing and removes the need to determine the best sequence‐alignment method, substitution matrix, and gap parameters for each unique pair of homologs. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Growth Phase Regulation of Vibrio cholerae RTX Toxin Export

ABSTRACT Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, secretes several “accessory” toxins, including RTX toxin, which causes the cross-linking of the actin cytoskeleton. RTX toxin is exported to the extracellular milieu by an atypical type I secretion system (T1SS), and we previously noted that RTX-associated activity is detectable only in supernatant fluids from log phase cultures. Here, we investigate the mechanisms for regulating RTX toxin activity in supernatant fluids. We find that exported proteases are capable of destroying RTX activity and may therefore play a role in the growth phase regulation of toxin activity. We determined that the absence of RTX toxin in stationary-phase culture supernatant fluids is also due to a lack of toxin secretion and not attributable to solely proteolytic degradation. We ascertained that the T1SS apparatus is regulated at the transcriptional level by growth phase control that is independent of quorum sensing, unlike other virulence factors of V. cholerae. Additionally, in stationary-phase cultures, all RTX toxin activity is associated with bacterial membranes or outer membrane vesicles.
Cardiac Monitoring: Hospital-wide Education and Staff Competence

Background:The numbers of patients in acute care hospitals who require cardiac monitoring are increasing. Unpredictable fluctuations in patient flow may result in shortages of telemetry beds for patients who need this level of care. Objective:The aims of this study were to design and implement cardiac monitoring education for all medical-surgical nursing staff in a level I trauma center. Methods:This is a descriptive, quantitative performance improvement study. A multidisciplinary implementation plan was developed with biomedical engineering and physical facilities coordinating structural changes and nursing coordinating education and clinical competency. The nursing educational plans included a dysrhythmia course and testing, a clinically based competency, and a statistical analysis of the dysrhythmia test. The impact of this project was evaluated looking at areas transitioned, telemetry beds available, cardiac dysrhythmia education workshops, and dysrhythmia test results. Results:The implementation of cardiac monitoring was completed over 2 years. Monitored medical-surgical beds increased from 132 to 282 beds. The nursing education expanded hospital-wide to clinical areas requesting standardization of nursing practice. Conclusions:In addition to expanding the number of monitored beds and decompression of critical care beds, benefits included increased level of staff competence, standardization of cardiac monitoring practices throughout the facility, and validation of the cardiac dysrhythmia test.
MET receptor is overexpressed but not mutated in oral squamous cell carcinomas

Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF‐induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive‐metastatic behavior. © 2001 Wiley‐Liss, Inc.
Antagonistic roles for Ultrabithorax and Antennapedia in regulating segment-specific apoptosis of differentiated motoneurons in the Drosophila embryonic central nervous system

The generation of morphological diversity among segmental units of the nervous system is crucial for correct matching of neurons with their targets and for formation of functional neuromuscular networks. However, the mechanisms leading to segment diversity remain largely unknown. We report here that the Hox genes Ultrabithorax (Ubx) and Antennapedia (Antp) regulate segment-specific survival of differentiated motoneurons in the ventral nerve cord of Drosophila embryos. We show that Ubx is required to activate segment-specific apoptosis in these cells, and that their survival depends on Antp. Expression of the Ubx protein is strongly upregulated in the motoneurons shortly before they undergo apoptosis, and our results indicate that this late upregulation is required to activate reaper-dependent cell death. We further demonstrate that Ubx executes this role by counteracting the function of Antp in promoting cell survival. Thus, two Hox genes contribute to segment patterning and diversity in the embryonic CNS by carrying out opposing roles in the survival of specific differentiated motoneurons.
Selective collection enrichment in user-centred health information retrieval

Due to the increasing amount of electronic information, a majority of laypeople (ordinary people with no professional medical knowledge) now rely on the Web to seek for health information for self-diagnosis. However, research has shown that current search engines are failing to deliver effective search results due to the inability of laypeople to formulate good queries because of lack of domain knowledge and unfamiliarity with the medical vocabulary and concepts. This article attempts to address this by proposing a Selective Collection Enrichment approach that uses three different external resources to enrich a user query, thus generating three different expanded queries. In addition, we deploy pre-retrieval query performance predictors to select an expanded query that is most likely to perform better when retrieving on a local collection being searched. Furthermore, we evaluate the effects of combining several pre-retrieval query performance predictors' scores using data fusion techniques for Selective Collection Enrichment. Our empirical evaluation shows marked improvement in the retrieval performance in terms of nDCG@10 when the Selective Collection Enrichment approach is deployed.
Comparison of Ehrlichia muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. muris as Antigen

ABSTRACT In metropolitan Tokyo, the Ehrlichia murisseropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had been isolated. These new isolates were compared with the E. muris type strain. The mouse virulence and ultrastructure of the new isolates were similar to those of the type strain, and all of them were cross-reactive with each other, as well as with the type strain, by indirect immunofluorescent-antibody test. The levels of similarity of the base sequences of the 16S rRNA gene of one of the A. speciosus isolates and one of the tick isolates to that of theE. muris type strain were 99.79 and 99.93%, respectively. We suggest that all of these isolates are E. muris; thatE. muris is not limited to Eothenomys kageusbut infects other species of mice; and that E. muris is present at locations other than Aichi Prefecture. It appears thatH. flava is a potential vector of E. muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be seropositive for E. muris antibodies. A serological survey revealed that exposure to E. muris or organisms antigenically cross-reactive to E. muris occurred among dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby prefectures, and Nagoya City, central Japan. However, human beings and Rattus norvegicus rats in this area were seronegative. These results indicate broader geographic distribution of and human and animal species exposure to E. muris or related Ehrlichia spp. in Japan.
Workplace bullying among nurses and their related factors in Japan: a cross-sectional survey.

AIMS AND OBJECTIVES To explore the association between workplace bullying and workplace environment factors among nurses in Japan. BACKGROUND Workplace bullying among nurses is increasing globally and occurs more frequently than among other professions. However, there is little information on the impact of workplace environment factors on nurse bullying in Japan. DESIGN A cross-sectional survey using a self-administered questionnaire. METHODS Participants were 1152 nurses recruited at seminars or training courses outside of their workplaces in Tokyo. Workplace bullying was measured using the Negative Acts Questionnaire-Revised. Participants were considered to have been 'bullied' if they reported experiencing at least one negative act on a daily or weekly basis. Workplace environment factors were measured using the Practice Environment Scale of the Nursing Work Index, which comprises five domains: nurse participation in hospital affairs; nursing foundations for quality of care; nurse manager ability, leadership and support of nurses; staffing and resource adequacy; and collegial nurse-physician relationships. RESULTS A total of 898 (78·0%) questionnaires were returned, of which 825 (71·6%) were analysed. Altogether, 153 (18·5%) nurses were considered 'bullied. ' The three most frequent negative acts reported as occurring on a weekly or daily basis were 'someone withholding information which affects your performance' (6·7%), 'being exposed to an unmanageable workload' (4·4%) and 'being shouted at or being the target of spontaneous anger (or rage)' (3·6%). Logistic regression analysis indicated that 'bullied' were associated with low scores on two work environment domains: nurse manager ability, leadership and support of nurses and staffing and resource adequacy. CONCLUSIONS Effective nurse manager leadership and support as well as appropriate staffing management may positively influence workplace bullying among nurses in Japan. Authentic leadership styles and allowing nurses to easily request days off might also be important. RELEVANCE TO CLINICAL PRACTICE Nurse managers' leadership may influence nurses' workplace bullying.
Cryogenic Performance of a Low-Noise JFET-CMOS Preamplifier for HPGe Detectors

Cryogenic low-noise charge sensitive preamplifiers have been developed and realized for the GERmanium Detector Array (GERDA). An integrated JFET-CMOS preamplifier, which is fully functional at cryogenic temperatures, has been tested in conjunction with an unsegmented p-type HPGe detector. Both the crystal and the preamplifier were operated inside a liquid nitrogen dewar at 77 K. The detector capacitance was ~60 pF. An optimum resolution of 1.6 keV FWHM has been obtained for the pulser line at 6 ¿s shaping time. A resolution of 2.1 keV FWHM has been achieved for the 1.332 MeV line from a 60Co source. A wide bandwidth (rise time of ~16 ns) permits use of pulse-shape analysis techniques to localize the position of the photon interactions inside the crystal. A low power consumption (~23 mW) makes the preamplifier suitable for a multi-channel array of germanium detectors.
Binge Drinking Trajectory and Decision-Making during Late Adolescence: Gender and Developmental Differences

Objective: Impaired affective decision-making has been consistently related to alcohol dependence. However, less is known about decision-making and binge drinking (BD) in adolescents. The main goal of this longitudinal study was to determine the association between BD and decision-making from late adolescence to early adulthood. A second aim is to assess developmental changes and performance differences in males and females. Method: An initial sample of 155 1st-year university students, (76 non-BDs, 40 females; and 79 BDs, 39 females), was followed prospectively over a 4-year period. The students were classified as stable non-BDs, stable BDs and ex-BDs according to their scores in item 3 of the AUDIT and the speed of alcohol consumption. Decision-making was assessed by the Iowa Gambling Task (IGT) three times during the study. Dependent variables were net gain and net loss. Results were analyzed using generalized linear mixed models. Results: A stable BD pattern was not associated with either disadvantageous decision-making or sensitivity to loss frequency. Performance improved significantly in both genders over the study period, especially in the last blocks of the task. Females showed a higher sensitivity to loss frequency than males. No gender-related differences were observed in gains. Conclusion: Performance in affective decision-making continues to improve in late adolescence, suggesting neuromaturational development in both genders. Females are more sensitive to loss frequency. Stable BD during late adolescence and emerging adulthood is not associated with deficits in decision-making. Poor performance of the IGT may be related to more severe forms of excessive alcohol consumption.
Metabotropic glutamate receptor subtype 1 regulates sodium currents in rat neocortical pyramidal neurons

Brain sodium channels (NaChs) are regulated by various neurotransmitters such as acetylcholine, serotonin and dopamine. However, it is not known whether NaCh activity is regulated by glutamate, the principal brain neurotransmitter. We show here that activation of metabotropic glutamate receptor (mGluR) subtype 1 regulates fast transient (INaT) and persistent Na+ currents (INaP) in cortical pyramidal neurons. A selective agonist of group I mGluR, (S)‐3,5‐dihydroxyphenylglycine (DHPG), reduced action potential amplitude and decreased INaT. This reduction was blocked when DHPG was applied in the presence of selective mGluR1 antagonists. The DHPG‐induced reduction of the current was accompanied by a shift of both the inactivation curve of INaT and the activation curve of INaP. These effects were dependent on the activation of PKC. The respective role of these two regulatory processes on neuronal excitability was determined by simulating transient and persistent Na+ conductances (GNaT and GNaP) with fast dynamic‐clamp techniques. The facilitated activation of GNaP increased excitability near the threshold, but, when combined with the down‐regulation of GNaT, repetitive firing was strongly decreased. Consistent with this finding, the mGluR1 antagonist LY367385 increased neuronal excitability when glutamatergic synaptic activity was stimulated with high external K+. We conclude that mGluR1‐dependent regulation of Na+ current depresses neuronal excitability, which thus might constitute a novel mechanism of homeostatic regulation acting during intense glutamatergic synaptic activity.
Transmastoid Decompression of the Facial Nerve in Temporal Bone Fracture

Among 41 cases of facial palsy caused by closed head injury, temporal bone fractures were surgically confirmed in 36 cases, of which there were two mixed fractures and 34 longitudinal fractures. The fracture involved the geniculate ganglion area in 20 cases (55%). In 15 cases, decompression of the facial nerve was carried out using the transmastoid supralabyrinthine approach with disarticulation of the incus; in only five cases was the middle fossa approach used. The technique avoids the craniotomy for the middle fossa approach and is a reliable method of treatment in the majority of patients with facial palsy caused by temporal bone fracture involving the geniculate ganglion area.
Pulsed laser activated cell sorter with dielectrophoretic single stream sheathless focusing

We report a novel sheathless microfluidic fluorescence-activated cell sorter utilizing size-independent three-dimensional dielectrophoretic (DEP) single stream focusing and pulsed laser activated cell sorting (PLACS). This is realized by fabricating a 3D microfluidic device using two glass substrates with patterned electrodes sandwiching a thin and open PDMS channel. DEP forces are provided along a 4cm-long channel that focuses particles into a single stream passing through a fluorescence detection zone regardless of their sizes and types at high flow speeds. Pulsed laser-induced cavitation bubbles are used to provide rapid (∼30 μs) and precise fluid perturbation to sort out particles upon the detection of fluorescence. High purity sorting has been accomplished at a throughput of 1500 particles sec−1.
99mTc‐HMPAO (Ceretec) is stored in and released from the granules of eosinophil granulocytes

99mTc‐HMPAO (Ceretec) labelling of leucocytes is used clinically for the detection of inflammatory processes in the body. This study investigated the mechanisms by which 99mTc‐HMPAO is taken up by eosinophils and neutrophils. Blood cells were labelled with 99mTc‐HMPAO and the cells separated by means of their densities in Percoll gradients. For other purposes, eosinophils and neutrophils were purified by means of the MACS system and, after labelling these pure cellular preparations, the cells were ultrasonicated and the organelles separated on sucrose density gradients by means of ultracentrifugation. Organelles were characterized by their morphology on electron microscopy. Granulocytes were stimulated to secrete their granule constituents by means of exposure to complement‐coated particles. ECP (eosinophil cationic protein) and MPO (myeloperoxidase) were measured using specific immunoassays. The uptake of 99mTc‐HMPAO was 15–25‐fold higher in eosinophils than in other leucocytes. 99mTc‐HMPAO was predominantly stored in the secretory granules of eosinophils and released from the eosinophil, upon activation, together with ECP. A second storage compartment was a very light density organelle of unknown nature. These results indicated that, among leucocytes, 99mTc‐HMPAO is preferentially taken up by eosinophils and stored in the secretory granules, which has to be taken into consideration when evaluating images based on this technique. Our findings suggest that 99mTc‐HMPAO (Ceretec) may be used as a tool to follow eosinophil turnover and activity in disease.