Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster

Alternative polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3′UTRs and/or coding sequences from a single gene. Here, using 3′ region extraction and deep sequencing (3′READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in Drosophila melanogaster, expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. Cis-element analysis revealed distinct sequence motifs around fly PASs when compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements. We found that over 75% of mRNA genes in Drosophila melanogaster undergo APA. The head tissue tends to use distal PASs when compared to the body, leading to preferential expression of APA isoforms with long 3′UTRs as well as with distal terminal exons. The distance between the APA sites and intron location of PAS are important parameters for APA difference between body and head, suggesting distinct PAS selection contexts. APA analysis of the RpII215C4 mutant strain, which harbors a mutant RNA polymerase II (RNAPII) with a slower elongation rate, revealed that a 50% decrease in transcriptional elongation rate leads to a mild trend of more usage of proximal, weaker PASs, both in 3′UTRs and in introns, consistent with the “first come, first served” model of APA regulation. However, this trend was not observed in the head, suggesting a different regulatory context in neuronal cells. Together, our data expand the PAS collection for Drosophila melanogaster and reveal a tissue-specific effect of APA regulation by RNAPII elongation rate.
Conserved SMP domains of the ERMES complex bind phospholipids and mediate tether assembly

Significance Phospholipid exchange between the endoplasmic reticulum (ER) and mitochondria is essential for membrane biogenesis and, ultimately, cell survival. It remains unclear, however, how this exchange is facilitated. Our study investigates a putative involvement of the ER-mitochondrial encounter structure (ERMES), a tethering complex that bridges the ER and mitochondria, in phospholipid transport in yeast. We show that a conserved ERMES domain called the “synaptotagmin-like mitochondrial lipid-binding protein” (SMP) domain preferentially binds phosphatidylcholines and mediates the hierarchical assembly of the tether. The 17-Å-resolution EM structure of the complex formed between the SMP domains present in two ERMES subunits, Mdm12 and Mmm1, reveals an elongated, tubular-shaped heterotetramer traversed by a hydrophobic channel, suggesting a mechanism for lipid transport between the two organelles. Membrane contact sites (MCS) between organelles are proposed as nexuses for the exchange of lipids, small molecules, and other signals crucial to cellular function and homeostasis. Various protein complexes, such as the endoplasmic reticulum-mitochondrial encounter structure (ERMES), function as dynamic molecular tethers between organelles. Here, we report the reconstitution and characterization of subcomplexes formed by the cytoplasm-exposed synaptotagmin-like mitochondrial lipid-binding protein (SMP) domains present in three of the five ERMES subunits—the soluble protein Mdm12, the endoplasmic reticulum (ER)-resident membrane protein Mmm1, and the mitochondrial membrane protein Mdm34. SMP domains are conserved lipid-binding domains found exclusively in proteins at MCS. We show that the SMP domains of Mdm12 and Mmm1 associate into a tight heterotetramer with equimolecular stoichiometry. Our 17-Å-resolution EM structure of the complex reveals an elongated crescent-shaped particle in which two Mdm12 subunits occupy symmetric but distal positions at the opposite ends of a central ER-anchored Mmm1 homodimer. Rigid body fitting of homology models of these SMP domains in the density maps reveals a distinctive extended tubular structure likely traversed by a hydrophobic tunnel. Furthermore, these two SMP domains bind phospholipids and display a strong preference for phosphatidylcholines, a class of phospholipids whose exchange between the ER and mitochondria is essential. Last, we show that the three SMP-containing ERMES subunits form a ternary complex in which Mdm12 bridges Mmm1 to Mdm34. Our findings highlight roles for SMP domains in ERMES assembly and phospholipid binding and suggest a structure-based mechanism for the facilitated transport of phospholipids between organelles.
Dementia Care and Respite Services Program

In 1987 The Robert Wood Johnson Foundation announced the creation of the Dementia Care and Respite Services Program (DCRSP), the first national demonstration project to focus on day center and respite services for persons with dementia. The intent of this $5.1 million, 4-year (1988–1992) program was to demonstrate that nonprofit day centers could provide financially viable programs and services needed by people with dementia and their caregivers. Seventeen grantees in 13 states, representing 21 different organizations and operating 24 day centers, participated in the project throughout the entire 4 years. The DCRSP has provided the first overview of dementia-specific day programs in the United States, with specific insight as to who is being served (e.g., participant and caregiver characteristics), types of assistance needed in relation to activities of daily living, and the most common behavior problems being exhibited. In addition, results of the 4-year project support the fact that community-based day centers can effectively care for people with dementia, a demand for these services does exist, and families consider these services of sufficient value that they are willing to pay for them out-of-pocket. Results also show that nonprofit day centers can become financially viable programs if attention is given to factors such as providing consumer-responsive services, charging what services actually cost, and having a high level of community visibility. The net result is increased net operating revenue with improved financial performance and enhanced long-term stability.
An Edge-Enhancing Crystal Growth Instability Caused by Structure-Dependent Attachment Kinetics

We describe a novel crystal growth instability that enhances the development of thin edges, promoting the formation of plate-like or hollow columnar morphologies. This instability arises when diffusion-limited growth is coupled with structure-depdendent attachment kinetics, specifically when the nucleation barrier on a facet surface decreases substantially as the facet width approaches atomic dimensions. Experimental data are presented confirming the presence of this instability in the growth of ice from water vapor at -15 C. We believe this edge-enhancing effect plays an important role in determining the growth morphologies of atmospheric ice crystals as a function of temperature, a phenomenon that has been essentially unexplained for over 75 years. Our model of structure-dependent attachment kinetics appears to be related to surface melting, and thus may be present in other material systems, whenever crystal growth from the vapor phase occurs near the material melting point.
Hereditary spastic paraplegia: a novel mutation and expansion of the phenotype variability in SPG10

of 3 per year (range 0–48.3). A literature review of UK medical meetings during a similar time period revealed variable rates of eventual publication. Weale et al found publication rates of 24–54% across four surgical meetings. A study of emergency medicine identified a publication rate of 30%, with platform presentations more likely to be published. Oral and maxillofacial surgery abstracts from 2001 to 2007 were published in 24% of cases, with scientific versus clinical presentations more likely to achieve eventual publication. Urology abstracts from 2001 to 2002 were published in 42% cases. Strengths of our study include surveying a large number of abstracts, a relatively long follow-up time and a robust search methodology consistent with previous work on this subject. A potential limitation is that we were unable to determine how many abstracts were submitted for full publication but eventually rejected, or never submitted at all, as this would have required extensive surveying of all authors presenting at the ABN. Our findings emphasise the importance of collaborative work in achieving high-quality research and publication. However, it is possible that this represents a surrogate of other factors, for example case reports may be likely to be single-centre work. While impact factors are a controversial metric of research quality, the majority of eventually published work following presentation at the ABN contributed to the scientific literature in the form of subsequent citations.
Unified fractional Fourier transform and sampling theorem

The fractional Fourier transform (FRT) is an extension of the ordinary Fourier transform (FT). Applying the language of the unified FT, we develop FRT expressions for discrete and continuous signals, introducing a particular form of periodicity: chirp-periodicity. The FRT sampling theorem is derived as an extension of its ordinary counterpart.
Fos response of fetal sheep anterior circumventricular organs to osmotic challenge in late gestation

McDonald, T. J., C. Li, M. J. M. Nijland, A. CastonBalderrama, and M. G. Ross. Fos response of fetal sheep anterior circumventricular organs to osmotic challenge in late gestation. Am. J. Physiol. 275 (Heart Circ. Physiol. 44): H609–H614, 1998. —We hypothesized that the anterior circumventricular organs (ACVO) and the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN), among other structures that play a role in sensing extracellular body fluid volume and composition in postnatal animals (as demonstrated by Fos protein production by the immediate-early gene c-fos), would show similar activation in fetal sheep during an osmotic challenge. The brains of 10 fetal sheep [6 treated, 4 controls; 129–131 days of gestational age (dGA) 5 0.87 gestation] were immunostained for Fos. Seventy-five minutes before tissue collection the dams were given intravenous 20% mannitol (1 ml·min21 ·kg21 for 10 min). Subsequently, the ACVO, SON, and PVN were scored for the amount of neuronal Fos immunostaining. The subfornical organ (SFO; 24.5 6 9.0 vs. 1.7 6 1.2), the organum vasculosum of the lamina terminalis (OVLT; 26.8 6 5.6 vs. 7.0 6 2.0), the SON (39.8 6 3.0 vs. 0.15 6 0.1), and the PVN (59.8 6 7.9 vs. 0.7 6 0.7) had increases (P , 0.05) in the average number of Fos-positive cells per field compared with controls, whereas the median preoptic nucleus did not. Double immunostaining for Fos and arginine vasopressin (AVP) or oxytocin (OT) indicated that AVPbut not OT-immunopositive neurons in SON and PVN respond to osmotic challenge. These results demonstrate that the SFO, OVLT, SON, and PVN are activated by osmotic challenge in fetal sheep at 130 dGA.
Patient-prosthesis mismatch in elderly patients undergoing aortic valve replacement: impact on quality of life and survival.

BACKGROUND AND AIM OF THE STUDY Since the introduction of its theoretical basis, patient-prosthesis mismatch (PPM) following aortic valve replacement (AVR) has been the subject of much debate. The study aim was to compare, by a propensity score adjustment, the survival and quality of life in elderly patients with PPM, to those of a population without mismatch. The analysis was focused on elderly patients, as their high prevalence of calcific aortic stenosis may increase the probability to receive a small-sized aortic prosthesis, and consequently to experience postoperative PPM. METHODS A total of 163 patients aged > or = 75 years who underwent AVR was analyzed. The median logistic euroSCORE was 7.1%. PPM was considered to be present if the anticipated indexed effective orifice area (IEOA) was < or = 0.85 cm2/m2. The median follow up period was 37.4 months. The patients' quality of life was evaluated using the Short Form 12 (SF-12) Health Survey test. RESULTS PPM was present in 43% of the patients. In multivariable analysis, patients with PPM were more often female, more often operated on for aortic degenerative calcification, had a larger body surface area, and more often received a bioprosthesis than those without mismatch. The survival analysis did not highlight any significant difference between the two groups. According to a multivariable analysis, the SF-12 physical component score of PPM patients was significantly inferior to that in patients without mismatch (p = 0.001). CONCLUSION The study results suggest that moderate PPM does not have a negative impact on mid-term mortality in elderly patients after AVR. However, PPM was associated with a reduced quality of life in this elderly population.
Estimation of type‐specific anti‐streptococcal M‐protein antibodies with biotinylated peptides in human sera

The design of a novel enzyme‐linked immunosorbent assay for the estimation of antibodies directed against the N‐terminus of the M‐protein of Streptococcus pyogenes is described. The ELISA employs biotinylated peptide antigens of the types 1, 4, 12 and 19 immobilized by (strept‐)avidin on the surface of polystyrene microtiter wells. In rabbit hyperimmune sera and in human serum samples, antibodies against the corresponding serotype could be detected with high sensitivity and specificity.
Influence du statut azoté et du cycle lumineux diurne sur le métabolisme lipidique d'Isochrysis sp. (Haptophyceae). (Influence of nitrogen status and light / dark cycle on Isochrysis sp. (Haptophyceae) lipid metabolism)

Cette these presente differents cas d'acclimatation d'une espece de phytoplancton (Isochrysis sp.) a des modifications de son environnement physico-chimique avec une attention particuliere portee sur la composante lipidique de la reponse aux changements. Dans ce contexte nous avons etudie les lipides a la fois comme des produits (triacylglycerol) et des acteurs (glycolipides) de la photosynthese. Tout d'abord, nous avons etudie l'influence de plusieurs types de limitation par l'azote sur la teneur en lipides neutres des algues. Nous avons montre que la relation entre la disponibilite de l'azote et la teneur en lipide n'etait pas monotone et qu'elle presentait un caractere hysteretique. Les cellules d'Isochrysis sp. n'accumulent des lipides neutres que transitoirement lors du passage d'une croissance forte vers une croissance faible. Nous nous sommes ensuite interesse aux relations qui existent entre le cycle nycthemeral et l'accumulation de reserves energetiques sous forme de lipides et de sucres. Les reserves sont accumulees pendant le jour en disproportion du reste du carbone et consommees pendant la nuit pour alimenter la division cellulaire et la croissance nocturne. La carence en azote dans ces conditions nycthemerales ne provoque pas d'accumulations significatives de lipides. Les variations diurnes de la teneur en lipides neutres sont plus importantes que les variations obtenues en carence. A travers ces differentes experiences nous avons pu mettre en evidences les relations qui existaient entre l'environnement, la croissance, et l'accumulation de reserves. La comprehension de ces mecanismes a permis de determiner les conditions environnementales qui favorisent la production d'huile en vue d'une utilisation biocarburant. Nous avons aussi etudie l'influence des conditions de croissance sur la composition des glycolipides des membranes des chloroplastes. Les resultats montrent que les changements de la teneur en MGDG, DGDG et SQDG et de l'insaturation des acides gras de ces lipides accompagnent les modifications d'activite photosynthetique des cellules en limitation azotee et en cycle Jour/Nuit.
Recovering from disaster: Comparing the experiences of nurses and general practitioners after the Canterbury, New Zealand earthquake sequence 2010–2011

This paper summarizes, elaborates upon, and contrasts the findings of two research projects that explored how general practitioners and nurses coped with the dual challenge of personal and work demands following the earthquakes in Canterbury, New Zealand, in 2010 and 2011. Qualitative data from two separate studies - the first with general practitioners and the second with nurses - are compared to identify the challenges faced during and following the earthquakes. Semi-structured interviews took place with eight general practitioners two years after the start of the earthquake sequence and 11 nurses a year later to enable exploration of the longer-term aspects of the recovery process. The interview transcripts were analyzed and coded using a constructivist grounded theory approach. The analysis identified that the earthquakes had a significant impact on nurses and general practitioners both in terms of their professional and personal lives. The nurses and general practitioners commented on the emotional impact and their support needs, as well as some of the longer-term recovery issues.
TLX1/HOX11 transcription factor inhibits differentiation and promotes a non‐haemopoietic phenotype in murine bone marrow cells

The TLX/HOX11 subfamily of divergent homeobox genes are involved in various aspects of embryogenesis and, in the case of TLX1/HOX11 and TLX3/HOX11L2, feature prominently as oncogenes in human T‐cell acute lymphoblastic leukaemia. TLX1 possesses immortalising activity in a wide variety of blood cell lineages, however, the effect of this oncogene on haemopoietic cell differentiation has not been fully investigated. We therefore constitutively expressed TLX1 in murine bone marrow or fetal liver cells using retroviral transfer followed by transplantation and/or in vitro culture. TLX1 was found to dramatically alter haemopoiesis, promoting the emergence of a non‐haemopoietic CD45− CD31+ cell population while markedly inhibiting erythroid and granulocytic cell differentiation. To identify genetic programs perturbed by TLX1, a comparison of transcript profiles from J2E erythroid cells with and without enforced TLX1 expression was undertaken. This revealed a pattern of gene expression indicative of enhanced proliferation coupled to differentiation arrest. Of the genes identified, two, KIT and VEGFC, were found to be potential TLX1 targets based on transcriptional assays. These results demonstrate that TLX1 can act broadly to impair haemopoiesis and divert differentiation to an alternative fate. This may account for its ability to promote the pre‐leukaemic state via perturbation of specific gene expression programs.
Clinical outcome of a pilot efficacy study on recombinant human follicle-stimulating hormone (Org 32489) combined with various gonadotrophin-releasing hormone agonist regimens.

In total, 50 couples participated in a pilot study evaluating the efficacy of various regimens of gonadotrophin-releasing hormone agonist (GnRHa) in association with recombinant human follicle-stimulating hormone (recFSH) in women undergoing in-vitro fertilization (IVF) and embryo transfer. The women were treated with recFSH alone (group I), or with recFSH in conjunction with pituitary desensitization using a buserelin intranasal spray, 4 x 150 micrograms per day, in a short protocol (group II) or in a long protocol (group III), or using triptorelin in a long protocol, giving a single dose of 3.75 mg i.m. (group IV) or daily s.c. injections of 200 micrograms (group V). In all women, treatment with recFSH resulted in multiple follicular growth and rises of serum inhibin and oestradiol. The latter indicates that the amount of remaining luteinizing hormone (LH) was sufficient to support FSH-induced oestrogen biosynthesis. On the day of human chorionic gonadotrophin (HCG) administration, endogenous LH was most profoundly suppressed in subjects treated with triptorelin. The median number of ampoules and treatment days required in the various treatment groups varied from 21 to 36 ampoules and from 7 to 14 days, respectively. The median number of oocytes per group ranged from 9 to 11 and all cumulus-corona-oocyte complexes, with the exception of two, were classified as mature. The median fertilization and cleavage rates ranged between the treatment groups from 40 to 73% and from 73 to 100%, respectively. Fertilization failure of retrieved oocytes occurred in six couples with andrological or unexplained infertility. One patient had no transfer because of insufficient embryo quality. (ABSTRACT TRUNCATED AT 250 WORDS)
Associations Between Parental Health Literacy, Use of Asthma Management Plans, and Child’s Asthma Control

Background. There are some studies demonstrating the effectiveness of the provision of written asthma action plans in improving asthma outcomes. There exist little data on the ability of parents to use these plans to make asthma care decisions. Objective. To assess the associations between parental health literacy (HL), parental ability to use a written asthma management plan (WAMP), and child’s asthma control. Methods. Parents completed a survey with questions related to WAMPs and child’s asthma, a HL screening tool, and 5 asthma vignettes. For vignettes, parents identified asthma control zone and then made decisions about asthma management. WAMP scores were totaled (0-32) and converted to a percent correct score. Associations between parental HL, WAMP scores, child’s asthma control, and demographics were determined with independent t tests or 1-way analysis of variance, and chi-square tests. Variables significantly associated with WAMP scores or asthma control were included in multiple logistic regression or multiple linear regression analyses. Results. A total of 176 surveys were included; the mean ± SD WAMP score was 58.9% ± 22.2%, and 25% of respondents had limited HL. Of respondents’ children, 38% had not well/poorly controlled asthma. In multiple regression analysis controlling for education level, limited HL was significantly associated with WAMP score (b = 11.3, standard error 3.8, P = .004). WAMP score was not associated with asthma control. Limited HL was associated with poor asthma control in univariate analysis, but not in a logistic regression model controlling for other significant variables. Only unmarried marital status (adjusted odds ratio 4.4, 95% CI 1.8-10.8, P = .001) was associated with asthma control. Conclusion. HL is associated with parental ability to use WAMPs to respond to asthma scenarios. Parental HL may play a role in parents’ ability to appropriately use WAMPs.
Privacy Notions for Privacy-Preserving Distributed Data Mining : Foundations and Privacy Games

It is well understood that the huge volumes of data captured in recent years have the potential to underpin significant research developments in many fields. But, to realise these benefits, all relevant parties must be comfortable with how this data is shared. At the heart of this is the notion of privacy — which is recognised as being somewhat difficult to define. Previous authors have shown how privacy notions such as anonymity, unlinkability and pseudonymity might be combined into a single formal framework. In this paper we use and extend this work by defining privacy games for individual and group privacy within distributed environments. More precisely, for each privacy notion, we formulate a game that an adversary has to win in order to break the notion. Via these games, we aim to clarify understanding of, and relationships between, different privacy notions; we also aim to give an unambiguous understanding of adversarial actions. Additionally, we extend previous work via the notion of unobservability.