Miracle-dz/UniFAR-FTUs huggingface dataset:
Origin and Evolution of Rickettsial Plasmids

Background Rickettsia species are strictly intracellular bacteria that have undergone a reductive genomic evolution. Despite their allopatric lifestyle, almost half of the 26 currently validated Rickettsia species have plasmids. In order to study the origin, evolutionary history and putative roles of rickettsial plasmids, we investigated the evolutionary processes that have shaped 20 plasmids belonging to 11 species, using comparative genomics and phylogenetic analysis between rickettsial, microbial and non-microbial genomes. Results Plasmids were differentially present among Rickettsia species. The 11 species had 1 to 4 plasmid (s) with a size ranging from 12 kb to 83 kb. We reconstructed pRICO, the last common ancestor of the current rickettsial plasmids. pRICO was vertically inherited mainly from Rickettsia/Orientia chromosomes and diverged vertically into a single or multiple plasmid(s) in each species. These plasmids also underwent a reductive evolution by progressive gene loss, similar to that observed in rickettsial chromosomes, possibly leading to cryptic plasmids or complete plasmid loss. Moreover, rickettsial plasmids exhibited ORFans, recent gene duplications and evidence of horizontal gene transfer events with rickettsial and non-rickettsial genomes mainly from the α/γ-proteobacteria lineages. Genes related to maintenance and plasticity of plasmids, and to adaptation and resistance to stress mostly evolved under vertical and/or horizontal processes. Those involved in nucleotide/carbohydrate transport and metabolism were under the influence of vertical evolution only, whereas genes involved in cell wall/membrane/envelope biogenesis, cycle control, amino acid/lipid/coenzyme and secondary metabolites biosynthesis, transport and metabolism underwent mainly horizontal transfer events. Conclusion Rickettsial plasmids had a complex evolution, starting with a vertical inheritance followed by a reductive evolution associated with increased complexity via horizontal gene transfer as well as gene duplication and genesis. The plasmids are plastic and mosaic structures that may play biological roles similar to or distinct from their co-residing chromosomes in an obligate intracellular lifestyle.
Post-transcriptional and translational regulation of mRNA-like long non-coding RNAs by microRNAs in early developmental stages of zebrafish embryos

At the post-transcriptional and translational levels, microRNA (miRNA) represses protein-coding genes via seed pairing to the 3′ untranslated regions (UTRs) of mRNA. Although working models of miRNA-mediated gene silencing are successfully established using miRNA transfections and knockouts, the regulatory interaction between miRNA and long non-coding RNA (lncRNA) remain unknown. In particular, how the mRNA-resembling lncRNAs with 5′ cap, 3′ poly(A)-tail, or coding features, are regulated by miRNA is yet to be examined. We therefore investigated the functional interaction between miRNAs and lncRNAs with/without those features, in miRNA-transfected early zebrafish embryos. We observed that the greatest determinants of the miRNA-mediated silencing of lncRNAs were the 5′ cap and 3′ poly(A)-tails in lncRNAs, at both the post-transcriptional and translational levels. The lncRNAs confirmed to contain 5′ cap, 3′ poly(A)-tail, and the canonical miRNA target sites, were observed to be repressed in the level of both RNA and ribosome-protected fragment, while those with the miRNA target sites and without 5′ cap and 3′ poly(A)-tail, were not robustly repressed by miRNA introduction, thus suggesting a role as a miRNA-decoy.
Sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing.

BACKGROUND HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. OBJECTIVE To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. DESIGN Cross-sectional study. SETTING Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. SUBJECTS Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. RESULTS The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as 'weak positives', 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). CONCLUSIONS The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT.
NATURAL HISTORY OF PLAGUE : Perspectives from More than a Century of Research ∗

■ Abstract For more than a century, scientists have investigated the natural history of plague, a highly fatal disease caused by infection with the gram-negative bacterium Yersinia pestis. Among their most important discoveries were the zoonotic nature of the disease and that plague exists in natural cycles involving transmission between rodent hosts and flea vectors. Other significant findings include those on the evolution of Y. pestis; geographic variation among plague strains; the dynamics and maintenance of transmission cycles; mechanisms by which fleas transmit Y. pestis; resistance and susceptibility among plague hosts; the structure and typology of natural foci; and how landscape features influence the focality, maintenance, and spread of the disease. The knowledge gained from these studies is essential for the development of effective prevention and control strategies.
Green ballast water treatment utilizing waste heat recovery

This paper presents a novel green and cost-effective ballast water treatment system which will utilize waste heat from propulsion machinery for the destruction of microorganisms in the ballast water in a relatively short time. The high temperature recovered from propulsion machinery combined with the rapid destruction of microorganisms will make the new system more effective than the current similar Ballast Water Management Systems. The research will involve a combination of biological laboratory experiments, numerical simulations, and full scale machinery testing. The project has a potential to lead to the development of methods and knowledge for efficient energy utilization, effective destruction of microorganisms, and reliable methods for sampling and testing of water quality. The latest results obtained demonstrate that the proposed idea works efficiently and effectively, while offering a satisfactory verification with on-site biological experiments.
Tissue cage experiments with beta-lactam antibiotics in rabbits.

An animal model in which antibiotic concentrations can be meausred in intersittial fluid (IF) withdrawn from subcutaneous tissue cages has been used. Although the physiological significance of IF is not well established, this model allowed the comparison of 1) two pharmacological forms of the same drug (bacampicillin and ampicillin were compared after a single oral dose; and 2) drugs of the same group in a single i.m. injection study and in a cumulative effect study. These data provide new criteria for clinical choice of antibiotics. A rapid penetration into IF can be explained by a low degree of serum protein binding, but a highly bound drug is not restricted to the intravascular space. In this animal model we have also shown that an 0.25 h i.v. infusion of cephalothin induced higher IF levels than an i.v. bolus injection and an 1 h i.v. infusion. Using a single i.v. bolus injection of various cephalosporins, we have shown that a two open compartment model cannot explain both serum and IF data. Sustained late IF levels suggested the hypothesis of a deep compartment.
Factors influencing parenting in early childhood: a prospective longitudinal study focusing on change.

BACKGROUND Parenting influences child outcomes but does not occur in a vacuum. It is influenced by socio-economic resources, parental health, and child characteristics. Our aim was to investigate the relative importance of these influences by exploring the relationship between changing parental health and socio-economic circumstances and changes in parenting. METHODS Data collected from the Avon Longitudinal Study of Parents and Children were used to develop an eight-item parenting measure at 8 and 33 months. The measure covered warmth, support, rejection, and control and proved valid and reliable. Regression analysis examined changes in financial circumstance, housing tenure, marital status, social support, maternal health and depression, and their influence on parenting score. The final model controlled for maternal age, education, and baseline depression. RESULTS Most mothers reported warm, supportive parenting at both times. Maternal depression was the only variable for which both positive and negative change was associated with changes in parenting score. Less depression was associated with better parenting scores and more depression with worse parenting scores. Improvements in social support and maternal general health were both associated with improved parenting scores, but for neither of these variables was deterioration associated with deterioration in parenting scores. Worsening financial circumstances predicted deterioration in parenting score, but improvements were not predictive of improvements in parenting. CONCLUSIONS Programmes aiming to improve parental health and social support are likely to return greater dividends with regard to improving parenting than programmes that aim to reduce family poverty.
Effects of Medializing Calcaneal Osteotomy on Achilles Tendon Lengthening and Plantar Foot Pressures

Posterior tibial tendon insufficiency, or adult acquired flatfoot deformity, involves collapse of the longitudinal arch of the foot with ensuing changes in the bony architecture of the foot as well. While it is generally accepted that a medializing calcaneal osteotomy (MCO) is a very useful treatment for restoring the fallen arch, questions regarding the effects of this procedure upon plantar foot pressures and Achilles tendon length changes need to be answered. This study focuses on changes in plantar foot pressures and Achilles tendon length as the result of performing a MCO. Fourteen fresh-frozen cadaver legs were used to test the effects of MCO on Achilles tendon length changes 2 cm proximal to the Achilles tendon insertion on the calcaneus. Differential variable reluctance transducers were anchored in ventromedial, dorsomedial, dorsolateral, and ventrolateral positions of the Achilles tendon at the aforementioned level. The effects of the MCO on plantar foot pressures were assessed simultaneously using the Tekscan HR Mat. Axial loading (100 lbs) of each specimen was performed in neutral and dorsiflexion (15°). Data were gathered for Achilles tendon length changes and plantar foot pressures for three trials in both the neutral and dorsiflexed positions. A medializing calcaneal osteotomy (1 cm medial translation) was then performed and testing was repeated in the fashion outlined heretofore. Analysis of the data revealed that there was no significant increase in Achilles tendon length as a result of the MCO. The data also showed that average pressure over the first and second metatarsal regions of the forefoot decreased significantly after MCO. At the same time there was a significant increase in average pressure over the medial and lateral aspect of the heel. These findings suggest that the Achilles tendon aids in inversion of the forefoot without undergoing a significant increase in length change of Achilles tendon fibers in any of the regions tested.
Disposition of positively charged Bowman-Birk protease inhibitor conjugates in mice: influence of protein conjugate charge density and size on lung targeting.

The influence of conjugate charge density and size on the targeting of cationic Bowman-Birk inhibitor (BBI) conjugates to the lungs was studied in mice. The biodistribution of BBI, either as the native protein or in the conjugated form (conjugated to a dicationic, tetracationic, or polycationic carrier), indicated that by increasing the charge density of BBI conjugates, the lung accumulation of the conjugates administered intravenously (i.v.) can be increased. The order of lung accumulation in these studies was as follows: polycationic- > tetracationic- > dicationic-conjugated BBI > BBI. The influence of conjugate size on lung accumulation was studied in three experiments. First, the biodistribution of poly(D-lysine) carriers of equal charge density but different molecular weight demonstrated that lung accumulation of polycationic carriers increases with an increase in carrier size. Second, the biodistributions of BBI, tyramine-derivatized poly(D-lysine)3 kDa, and poly(D-lysine)3 kDa conjugated to BBI indicated that an increase in conjugate size alone is not sufficient to promote the lung accumulation of cationic BBI conjugates. Finally, the biodistribution poly(D-lysine) complexed with heparin showed that targeting of a conjugate to the lungs can be abolished by neutralizing the charge on the carrier. Collectively, data in this paper demonstrate that the carrier-mediated targeting of BBI to the lungs is dependent on (a) cationization of BBI, (b) the conjugate positive charge density, and (c) the size of the cationic conjugate if the charge density is maintained. Also, the data show the size of the conjugate alone does not make a significant impact on lung accumulation.
Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

Abstract Background: Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterised by progressive cerebellar ataxia, immunodeficiency, genetic instability, and cancer susceptibility. In addition, many patients suffer from growth failure. Methods: We analyzed growth and IGF-1/BP3 levels of 24 A-T-patients compared with an age-matched group of healthy controls (n = 36). Results: Ten (41.7%) A-T patients and none of healthy controls had an IGF-1 level below the 3rd percentile for age. The growth hormone (GH) stimulation tests revealed a severe GH deficiency with no increase of >5 ng/ml in six of the ten A-T patients. The IGF-1 generation tests revealed normal increases in IGF-1 values in all patients. Conclusion: Our results show that a disturbance in the GH/IGF-1 axis was present in 58.3% of A-T patients. Low levels of GH were the result of reduced central GH secretion. GH treatment may be a therapeutic option for A-T patients with severe growth failure.
Toll-Like Receptor Ligands Modulate Dendritic Cells to Augment Cytomegalovirus- and HIV-1-Specific T Cell Responses 1

Optimal Ag targeting and activation of APCs, especially dendritic cells (DCs), are important in vaccine development. In this study, we report the effects of different Toll-like receptor (TLR)-binding compounds to enhance immune responses induced by human APCs, including CD123+ plasmacytoid DCs (PDCs), CD11c+ myeloid DCs (MDCs), monocytes, and B cells. PDCs, which express TLR7 and TLR9, responded to imidazoquinolines (imiquimod and R-848) and to CpG oligodeoxynucleotides stimulation, resulting in enhancement in expression of costimulatory molecules and induction of IFN-α and IL-12p70. In contrast, MDCs, which express TLR3, TLR4, and TLR7, responded to poly(I:C), LPS, and imidazoquinolines with phenotypic maturation and high production of IL-12 p70 without producing detectable IFN-α. Optimally TLR ligand-stimulated PDCs or MDCs exposed to CMV or HIV-1 Ags enhanced autologous CMV- and HIV-1-specific memory T cell responses as measured by effector cytokine production compared with TLR ligand-activated monocytes and B cells or unstimulated PDCs and MDCs. Together, these data show that targeting specific DC subsets using TLR ligands can enhance their ability to activate virus-specific T cells, providing information for the rational design of TLR ligands as adjuvants for vaccines or immune modulating therapy.
Professional development as discourse change: teaching mathematics to English learners

This study examines teacher learning from the perspective of cultural–historical activity theory, which emphasizes the creation of new environments and new artefacts. This study focuses on elementary school teachers' learning over the course of professional development (PD) sessions for equitable mathematics teaching. Within the PD, the teachers created a student project that investigated linguistic diversity in the school community. Thematic analysis reveals that teachers' discourse relating to teaching mathematics to English language learners (ELLs) changed after the implementation of the inquiry project. More specifically, the discourse shifted from focusing on ELLs' barriers and challenges to highlighting what ELLs can do. This shift was coupled with a change in the classroom mathematics learning environment.
Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy

We have previously shown that myofibers formed by fusion of muscle satellite cells from spinal muscular atrophy (SMA) I or II undergo degeneration 1 to 3 weeks after innervation by rat embryonic spinal cord explants, whereas normal myofibers survive for several months. In the “muscle component” of the coculture, the only cells responsible for the degeneration are the SMA muscle satellite cells. Moreover, SMA muscle satellite cells do not fuse as rapidly as do normal muscle satellite cells. To determine whether death of muscle cells precedes that of motor neurons, we studied the origin and kinetics of release of apoptotic microparticles. In SMA cocultures, motor neuron apoptosis occurred before myofiber degeneration becomes visible, indicating that SMA myofibers were unable to sustain survival of motor neurons. In normal cocultures, motor neuron apoptosis occurred 4 days after innervation. However, it did not continue beyond 2 days. These results strengthen the hypothesis that SMA is due to a defect in neurotrophic muscle cell function. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
[Effects of caspases on cerebromicrovascular endothelial cell apoptosis induced by hypoxia].

AIM To study the effects of caspases on cerebromicrovascular endothelial cell apoptosis induced by hypoxia in vitro. METHODS The cultured bovine cerebromicrovascular endothelial cells were exposed to NaCN in glucose-free medium. Cell viability was determined by trypan blue staining. Cell apoptosis was defined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and flow cytometry. The expression of caspase-3 was detected by immunocytochemical method. Four caspase inhibitors were used to validate the effect of caspases on cell apoptosis. RESULTS NaCN in glucose-free medium initiated cerebromicrovascular endothelial cell injury markedly and typical apoptotic cells were found in this model. The expression of caspase-3 increased significantly. Four caspase inhibitors decreased the number of injured cells. Selective inhibitor of caspase-1 and -6 reduced expression of caspase-3 significantly. CONCLUSION The results suggest that caspases family plays an important role in cerebromicrovascular endothelial cell apoptosis induced by NaCN and caspase-3 acts on the downstream of caspase-1 and -6 in protease cascade action to induce apoptosis.
Osx transcriptional regulation is mediated by additional pathways to BMP2/Smad signaling

Bone morphogenetic protein (BMP)‐2 induces Osterix (Osx) in mouse C2C12 cells and chondrocytes. Genetic studies place Osx downstream to the BMP‐2/Smad/Runx2 signaling pathway; however, limited information is available on the mediators of Osx expression in osteoblast lineage commitment. Several lines of research implicate the presence of Runx2‐independent ossification. Therefore, the purpose of this study was to identify possible mediators of Osx expression beyond the BMP‐2/Smad pathway. Using real‐time RT‐PCR, we showed upregulation of Osx in response to BMP‐2 in human mesenchymal stem cells (hMSC). Insulin‐like growth factor (IGF)‐I upregulated Osx, but not Runx2. Further, IGF‐I in combination with BMP‐2 was synergistic for Osx, suggesting a pathway beyond Smad signaling. MAPK was tested as a common mediator across BMP‐2 and IGF‐I signaling pathways. Inhibition of MAPK component ERK1/2 did not affect Runx2 gene expression, but inhibited Osx expression and matrix mineralization. BMP‐2‐mediated Osx expression was downregulated in response to p38 inhibition. We therefore conclude that during osteogenic lineage progression, in addition to the BMP‐2/Smad pathway, IGF‐I and MAPK signaling may mediate Osx. © 2005 Wiley‐Liss, Inc.
The ‘Expansion–Contraction’ model of Pleistocene biogeography: rocky shores suffer a sea change?

Approximately 20 000 years ago the last glacial maximum (LGM) radically altered the distributions of many Northern Hemisphere terrestrial organisms. Fewer studies describing the biogeographic responses of marine species to the LGM have been conducted, but existing genetic data from coastal marine species indicate that fewer taxa show clear signatures of post‐LGM recolonization. We have assembled a mitochondrial DNA (mtDNA) data set for 14 co‐distributed northeastern Pacific rocky‐shore species from four phyla by combining new sequences from ten species with previously published sequences from eight species. Nuclear sequences from four species were retrieved from GenBank, plus we gathered new elongation factor 1‐α sequences from the barnacle Balanus glandula. Results from demographic analyses of mtDNA for five (36%) species (Evasterias troschelii, Pisaster ochraceus, Littorina sitkana, L. scutulata, Xiphister mucosus) were consistent with large population expansions occurring near the LGM, a pattern expected if these species recently recolonized the region. However, seven (50%) species (Mytilus trossulus, M. californianus, B. glandula, S. cariosus, Patiria miniata, Katharina tunicata, X. atropurpureus) exhibited histories consistent with long‐term stability in effective population size, a pattern indicative of regional persistence during the LGM. Two species of Nucella with significant mtDNA genetic structure showed spatially variable demographic histories. Multilocus analyses for five species were largely consistent with mtDNA: the majority of multilocus interpopulation divergence times significantly exceeded the LGM. Our results indicate that the LGM did not extirpate the majority of species in the northeastern Pacific; instead, regional persistence during the LGM appears a common biogeographic history for rocky‐shore organisms in this region.