Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation and Characterization of an Oridonin Nanosuspension for Solubility and Dissolution Velocity Enhancement

This study describes the preparation of an oridonin (ORI) nanosuspension by high-pressure homogenization (HPH). The aim was to obtain a stable nanosuspension with an increased drug saturation solubility and dissolution velocity. The homogenization procedure was optimized in regard to particle size and long-term stability. The characteristics of the oridonin nanosuspension, such as particle size, size distribution, shape, and zeta potential, were evaluated following the water removal. The solubility and dissolution experiments were performed to verify the obvious improvement of the dissolution behavior compared with commercial ORI. Finally, crystalline state evaluation before and following the formulation was performed through differential scanning calorimetry (DSC) and powder X-ray (PXRD).
Trapping Biases of Culex torrentium and Culex pipiens Revealed by Comparison of Captures in CDC Traps, Ovitraps, and Gravid Traps

ABSTRACT: We evaluate three trapping methods for their effectiveness at capturing Culex pipiens and Culex torrentium, both enzootic vectors of bird-associated viruses in Europe. The comparisons, performed in two regions in Sweden, were among CDC traps baited with carbon dioxide, gravid traps, and ovitraps baited with hay infusion. The proportions of the two Culex species in a catch differed between trap types, with CDC traps catching a lower proportion of Cx. torrentium than both gravid traps and ovitraps. Between gravid traps and ovitraps, there was no difference in the proportions of the two species. The results indicate that Cx. torrentium may go undetected or underestimated compared to Cx. pipiens when using carbon dioxide baited CDC traps. The new insight of trap bias presented here adds an important dimension to consider when investigating these vectors of bird-associated viruses in the field.
The ER-Localized TWD1 Immunophilin Is Necessary for Localization of Multidrug Resistance-Like Proteins Required for Polar Auxin Transport in Arabidopsis Roots[OA]

Members of the B group of ABC transporters are required for polar auxin transport through various plant tissues and organs. This report clarifies how the TWD1 immunophilin affects auxin transport and root growth by affecting B-group ABC transporters. Multidrug resistance ABC transporters in plants are required for polar transport of the hormone auxin (indole-3-acetic acid). They are studied in animals primarily because their overexpression confers resistance to anticancer agents. Immunophilins are studied in both plants and animals for their roles in folding and trafficking of proteins, particularly those with signal transducing functions and susceptibility to immunosuppressant drugs. Previous genetic and molecular studies in Arabidopsis thaliana established a physical and functional interaction between some ABCB transporters and the TWISTED DWARF1 (TWD1) immunophilin. In this work, confocal microscopy of fluorescently tagged TWD1 shows it to reside at the endoplasmic reticulum (ER). Mutations in TWD1 caused mislocalization of ABCB1, ABCB4, and ABCB19 to the ER instead of the plasma membrane as shown by confocal microscopy of fluorescently tagged fusion proteins and transmission electron microscopy of immunogold-labeled samples in the case of ABCB19. Localization of the unrelated PIN-FORMED2 auxin transporter or plasma membrane marker proteins was not affected by loss of TWD1. Abnormal spread of auxin signaling into the elongation zone of twd1 roots, attributable to mislocalized ABCB transporters and suppressed by an auxin transport inhibitor, appeared to cause the twisted cell files characteristic of twd1 roots.
Retrograde transport of [3H]glycine from the cochlear nucleus to the superior olive in the guinea pig

The origins of descending glycinergic projections to the guinea pig cochlear nucleus were investigated using retrograde labelling techniques. To identify the cell groups that provide descending projections to the cochlear nucleus, horseradish peroxidase, a nonspecific retrograde neuronal marker, was injected into the cochlear nucleus. After 24 or 48 hours, labelled cell bodies were evident bilaterally in all of the periolivary nuclei that surround the lateral and medial superior olive. The largest numbers of labelled neurons were located in the ventral nucleus of the trapezoid body bilaterally and in the lateral nucleus of the trapezoid body and dorsal periolivary nucleus ipsilaterally. Labelled cells were also present in the inferior colliculus bilaterally and in the contralateral cochlear nucleus. [3H]Glycine was employed as a retrograde tracer to identify the cell groups providing descending glycinergic projections to the cochlear nucleus. Three to 48 hours after injection of 19, 190, or 380 μM [3H]glycine into the cochlear nucleus, retrogradely labelled cell bodies were observed ipsilaterally in all of the periolivary nuclei. No labelled neurons were found in the inferior colliculus. After injections of the highest concentration of [3H]glycine, labelled cells were also found contralaterally in the ventral and lateral nuclei of the trapezoid body and also in the contralateral cochlear nucleus. We conclude that descending glycinergic projections to the cochlear nucleus originate mostly in ipsilateral periolivary cell groups. Minor glycinergic projections originate from the contralateral cochlear nucleus and also from the contralateral ventral and lateral nuclei of the trapezoid body.
Black and white and read all over: the past, present and future of giant panda genetics

Few species attract much more attention from the public and scientists than the giant panda (Ailuropoda melanoleuca), a popular, enigmatic but highly endangered species. The application of molecular genetics to its biology and conservation has facilitated surprising insights into the biology of giant pandas as well as the effectiveness of conservation efforts during the past decades. Here, we review the history of genetic advances in this species, from phylogeny, demographical history, genetic variation, population structure, noninvasive population census and adaptive evolution to reveal to what extent the current status of the giant panda is a reflection of its evolutionary legacy, as opposed to the influence of anthropogenic factors that have negatively impacted this species. In addition, we summarize the conservation implications of these genetic findings applied for the management of this high‐profile species. Finally, on the basis of these advances and predictable future changes in genetic technology, we discuss future research directions that seem promising for giant panda biology and conservation.
Expanders with Superquadratic Growth

We prove several expanders with exponent strictly greater than $2$. For any finite set $A \subset \mathbb R$, we prove the following six-variable expander results: $|(A-A)(A-A)(A-A)| \gg \frac{|A|^{2+\frac{1}{8}}}{\log^{\frac{17}{16}}|A|},$ $\left|\frac{A+A}{A+A}+\frac{A}{A}\right| \gg \frac{|A|^{2+\frac{2}{17}}}{\log^{\frac{16}{17}}|A|},$ $\left|\frac{AA+AA}{A+A}\right| \gg \frac{|A|^{2+\frac{1}{8}}}{\log |A|},$ $\left|\frac{AA+A}{AA+A}\right| \gg \frac{|A|^{2+\frac{1}{8}}}{\log |A|}. $
Impact of treatment for bacterial vaginosis on prematurity among Brazilian pregnant women: a retrospective cohort study.

CONTEXT AND OBJECTIVE Bacterial vaginosis has been associated with prematurity and other perinatal complications. However, the efficacy of the treatment for preventing such complications has not yet been well established. The objective of this study was to evaluate the impact of treatment for bacterial vaginosis on a low-risk population of Brazilian pregnant women, in order to prevent prematurity and other perinatal complications. DESIGN AND SETTING Observational retrospective cohort study, at the Obstetric and Gynecology Department, Universidade Estadual de Campinas (Unicamp). METHODS Vaginal bacterioscopy results from 785 low-risk pregnant women were studied. Three different groups of women were identified: 580 without bacterial vaginosis during pregnancy, 134 with bacterial vaginosis treated using imidazoles (metronidazole, tinidazole, or secnidazole) during pregnancy, and 71 with bacterial vaginosis not treated during pregnancy. The diagnosis of bacterial vaginosis was based on Nugent's criteria, from the vaginal bacterioscopy performed during the first prenatal care visit. RESULTS The frequency of prematurity was 5.5% among the women without bacterial vaginosis, 22.5% among those with untreated bacterial vaginosis and 3.7% among those with treated bacterial vaginosis. The risk ratios for perinatal complications were significantly higher in the group with untreated bacterial vaginosis: premature rupture of membranes, 7.5 (95% CI: 1.9-34.9); preterm labor, 3.4 (95% CI: 1.4-8.1); preterm birth, 6.0 (95% CI: 1.9-19.7); and low birth weight, 4.2 (95% CI: 1.2-14.3). CONCLUSION The treatment of bacterial vaginosis significantly reduced the rates of prematurity and other perinatal complications among these low-risk Brazilian pregnant women, regardless of the history of previous preterm delivery.
Safety assessment of potentially inappropriate medications use in older people and the factors associated with hospital admission.

PURPOSE Potentially Inappropriate Medications (PIM) use in elderly people may be responsible for the development of Adverse Drug Reaction (ADR) which, when severe, leads to hospital admissions. OBJECTIVES to estimate the prevalence of elderly who had used PIM before being admitted to hospital admission and to identify the risk factors and the hospitalizations related to ADR arising from PIM. METHODS A descriptive and cross-sectional study was performed in the internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of a validated form, patients aged ≥ 60 years, with length of hospital stay ≥ 24 hours, were interviewed about drugs taken prior to the hospital admission and the complaints/reasons for hospitalization. RESULTS 19.1% (59/308) of older patients had taken PIM before hospital admission and in 4.9%; there were a causal relation between the PIM taken and the complaint reported. PIM responsible for admissions were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin, estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0% of the clinical manifestations of PIM-related ADR were: dizziness, fatigue, digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor for the occurrence of ADR of PIM (p = 0.02). CONCLUSION PIM use in elderly people is not a risk factor for ADR-related hospital admission. Probably, severe ADR, which lead to hospitalizations of older people, can be explained by idiosyncratic response or the predisposition of these patients to develop adverse drug events, whether or not drugs are classed as PIM.
Fatigue associated EMG behavior of the first dorsal interosseous and adductor pollicis muscles in different groups of subjects

We have studied the fatigue‐associated behavior of surface EMG in two histochemically different muscles of the hand: first dorsal interosseous (FDI) and adductor pollicis (AP; relatively more type I fibers in AP than in FDI). During a fatigue test evoked by electrical stimulation of the ulnar nerve, the mean amplitudes of compound muscle action potentials (M‐waves) exhibited the same overall pattern for both muscles: a rapid phase of potentiation followed by a gradual decline. However, if the group of subjects was subdivided on the basis of hand length, significant differences emerged in the reactions of AP: in large hands, no fatigue‐associated M‐wave decline was seen, whereas in small hands a distinct decline was observed. A possible explanation for this phenomenon might be the presence of a greater amount of EMG contamination from other muscles in smaller hands. In the supposedly “cleaner” recordings from larger hands, significant differences between FDI and AP were observed with regard to their fatigue‐associated EMG reactions (M‐wave depression in FDI but not in AP). The direction of these differences was in accordance with expectations on the basis of known differences in histochemical fiber type composition. © 1994 John Wiley & Sons, Inc.
MDR1a/1b gene silencing enhances drug sensitivity in rat fibroblast‐like synoviocytes

Drug resistance mediated by P‐glycoprotein (P‐gp) is one of the major reasons for the failure of rheumatoid arthritis (RA) therapy with disease modifying anti‐rheumatic drugs and glucocorticoids. In the present study, we aimed to investigate the in vitro effectiveness of small interfering RNA (siRNA) to render rat fibroblast‐like synoviocytes (FLS) susceptible to drugs. We also attempted the electroporation‐mediated transfer of siRNA against multidrug resistance (MDR) genes into rat knee joints.
Creativity, psychosis and human evolution: The exemplar case of neuregulin 1 gene

gene that further adds to its significance in the context of creativity and psychosis from the perspectives of human evolution.Comparative genomic analyses examine a fundamental measure of the relative importance of selection and genetic drift in causing amino-acid substitutions is the dN/dS ratio (dN is a measure of the degree to which two homologous coding Deoxyribonucleic acid (DNA) sequences differ at non-synonymous sites, dS is a measure of the degree to which two homologous coding sequences differ with respect to silent nucleotide substitutions). Analyzing dN and dS are among the most direct ways to obtain evidence for positive selection on a protein-coding gene.
Non‐lipooligosaccharide‐mediated signalling via Toll‐like receptor 4 causes fatal meningococcal sepsis in a mouse model

Meningococcal lipooligosaccharide (LOS) is a major inflammatory mediator of fulminant meningococcal sepsis and meningitis with disease severity correlating with circulating concentrations of LOS and proinflammatory cytokines. In this study we show that the proinflammatory response to live meningococci in a mouse model of sepsis involves TLR4, but can develop independently of the expression of LOS. This is supported by data showing that in vivo an isogenic LOS‐deficient strain, lpxA, induced equivalent disease severity and similar proinflammatory responses as the serogroup C wild‐type parent strain FAM20. This response was abolished in TLR4–/– mice, and neither the wild‐type strain of meningococci nor the LOS‐deficient mutant was able to cause fatal sepsis in these mice. Mouse survival correlated with low levels of cytokines and chemokines, the chemotactic complement factor C5a and neutrophil levels in blood at 24 h post infection. These data suggest that during meningococcal sepsis the recognition of one or more unidentified non‐LOS component(s) by TLR4 is important in stimulating proinflammatory responses, and that fatality associated with meningococcal sepsis in mice is induced by the proinflammatory host response.
Comparative Genomics of Pathogenic and Nonpathogenic Beetle-Vectored Fungi in the Genus Geosmithia

Abstract Geosmithia morbida is an emerging fungal pathogen which serves as a model for examining the evolutionary processes behind pathogenicity because it is one of two known pathogens within a genus of mostly saprophytic, beetle-associated, fungi. This pathogen causes thousand cankers disease in black walnut trees and is vectored into the host via the walnut twig beetle. Geosmithia morbida was first detected in western United States and currently threatens the timber industry concentrated in eastern United States. We sequenced the genomes of G. morbida in a previous study and two nonpathogenic Geosmithia species in this work and compared these species to other fungal pathogens and nonpathogens to identify genes under positive selection in G. morbida that may be associated with pathogenicity. Geosmithia morbida possesses one of the smallest genomes among the fungal species observed in this study, and one of the smallest fungal pathogen genomes to date. The enzymatic profile in this pathogen is very similar to its nonpathogenic relatives. Our findings indicate that genome reduction or retention of a smaller genome may be an important adaptative force during the evolution of a specialized lifestyle in fungal species that occupy a specificniche, such as beetle vectored tree pathogens. We also present potential genes under selection in G. morbida that could be important for adaptation to a pathogenic lifestyle.
Natural acidification changes the timing and rate of succession, alters community structure, and increases homogeneity in marine biofouling communities

Ocean acidification may have far‐reaching consequences for marine community and ecosystem dynamics, but its full impacts remain poorly understood due to the difficulty of manipulating pCO2 at the ecosystem level to mimic realistic fluctuations that occur on a number of different timescales. It is especially unclear how quickly communities at various stages of development respond to intermediate‐scale pCO2 change and, if high pCO2 is relieved mid‐succession, whether past acidification effects persist, are reversed by alleviation of pCO2 stress, or are worsened by departures from prior high pCO2 conditions to which organisms had acclimatized. Here, we used reciprocal transplant experiments along a shallow water volcanic pCO2 gradient to assess the importance of the timing and duration of high pCO2 exposure (i.e., discrete events at different stages of successional development vs. continuous exposure) on patterns of colonization and succession in a benthic fouling community. We show that succession at the acidified site was initially delayed (less community change by 8 weeks) but then caught up over the next 4 weeks. These changes in succession led to homogenization of communities maintained in or transplanted to acidified conditions, and altered community structure in ways that reflected both short‐ and longer‐term acidification history. These community shifts are likely a result of interspecific variability in response to increased pCO2 and changes in species interactions. High pCO2 altered biofilm development, allowing serpulids to do best at the acidified site by the end of the experiment, although early (pretransplant) negative effects of pCO2 on recruitment of these worms were still detectable. The ascidians Diplosoma sp. and Botryllus sp. settled later and were more tolerant to acidification. Overall, transient and persistent acidification‐driven changes in the biofouling community, via both past and more recent exposure, could have important implications for ecosystem function and food web dynamics.
Intestinal microbiota in fishes: what's known and what's not

High‐throughput sequencing approaches have enabled characterizations of the community composition of numerous gut microbial communities, which in turn has enhanced interest in their diversity and functional relationships in different groups of vertebrates. Although fishes represent the greatest taxonomic and ecological diversity of vertebrates, our understanding of their gut microbiota and its functional significance has lagged well behind that of terrestrial vertebrates. In order to highlight emerging issues, we provide an overview of research on fish gut microbiotas and the biology of their hosts. We conclude that microbial community composition must be viewed within an informed context of host ecology and physiology, and that this is of particular importance with respect to research planning and sampling design.
Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting;

Flow cytometry to detect minimal residual disease is a sensitive and specific means to detect impending relapse in B lineage acute lymphoblastic leukemia (ALL). However as with all relatively sophisticated procedures assurance is needed that the methodology is widely applicable, and reproducible in different laboratories. In this paper, the UK ALL Flow MRD Group and the UK MRD steering group describe a four color flow protocol that was applicable to most patients and showed similarly high levels of concordance both between different laboratories and with MRD as detected molecularly. See related perspective article on page 748. Minimal residual disease detection, used for clinical management of children with acute lymphoblastic leukemia, can be performed by molecular analysis of antigen-receptor gene rearrangements or by flow cytometric analysis of aberrant immunophenotypes. For flow minimal residual disease to be incorporated into larger national and international trials, a quality assured, standardized method is needed which can be performed in a multi-center setting. We report a four color, flow cytometric protocol established and validated by the UK acute lymphoblastic leukemia Flow minimal residual disease group. Quality assurance testing gave high inter-laboratory agreement with no values differing from a median consensus value by more than one point on a logarithmic scale. Prospective screening of B-ALL patients (n=206) showed the method was applicable to 88.3% of patients. The minimal residual disease in bone marrow aspirates was quantified and compared to molecular data. The combined risk category concordance (minimal residual disease levels above or below 0.01%) was 86% (n=134). Thus, this standardized protocol is highly reproducible between laboratories, sensitive, applicable, and shows good concordance with molecular-based analysis.
Exploring prokaryotic diversity: there are other molecular worlds

Prokaryotes are the major source of biological diversity on earth. This is not simply because of the large number of species present, or because of their diverse growth conditions and environmental niches populated by them, but because of the wealth of genes, metabolic pathways and molecular processes that are only found in prokaryotic cells. Therefore, Bacteria and Archaea (and their phages) cannot be considered any longer as miniaturized models of Eukaryotes, but as a genuine source of unique biological processes that are mediated by unique sets of genes and molecular devices. A true understanding of complex biological phenomena will require a deeper knowledge of this vast prokaryotic world. The second European Molecular Biology Organization (EMBO) conference on Molecular Microbiology entitled ‘Exploring Prokaryotic Diversity’ explored many aspects of this newly emerging interest in the prokaryotic world.