Since gliotoxin is immunosuppressive and cytocidal 17, it can be speculated that the fungus benefits from nutrients released by the gliotoxin-destroyed host cells. Concluding Remarks Among the over ...200 species of Aspergillus, A. fumigatus is the best at meeting the four features discussed in this review. Since innate immunity protects against Aspergillus, the reason for the wide spread of IA caused by A. fumigatus is due to the global distribution of both the fungus and an increase in susceptible hosts.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Molecular phylogenetic analysis confirmed the phylum Zygomycota to be polyphyietic, and the taxa conventionally classified in Zygomycota are now distributed among the new phylum Glomeromycota and 4 ...subphyla incertae sedis (uncertain placement). Because the nomenclature of the disease zygomycosis was based on the phylum Zygomycota (Zygomycetes) in which the etiologic agents had been classified, the new classification profoundly affects the name of the disease. Zygomycosis was originally described as a convenient and inclusive name for 2 clinicopathologically different diseases, mucormycosis caused by members of Mucorales and entomophthoramycosis caused by species in the order Entomophthorales of Zygomycota. Without revision of original definition, the name "zygomycosis," however, has more often been used as a synonym only for mucormycosis. This article reviews the progress and changes in taxonomy and nomenclature of Zygomycota and the disease zygomycosis. The article also reiterates the reasons why the classic names "mucormycosis" and "entomophthoramycosis" are more appropriate than "zygomycosis."
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BFBNIB, NUK, PNG, UL, UM, UPUK
We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of ...metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography‐electrospray ionization‐tandem mass spectrometry. When metformin was co‐administered with pyrimethamine, its area under the concentration–time curve from 0 to 12 h was 2.58‐fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2‐h‐post‐OGTT serum glucose concentration were −0.6 (−1, −0.2), −0.9 (−1.6, −0.3) and −0.5 (−1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal‐based pharmacology of metformin.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In 1961, Segre and Silberberg first reported the tubular pinch effect and numerous theoretical studies were subsequently published to explain the inertial particle migration phenomenon. Presently, as ...fluid mechanics meets micro- and nanotechnology, theoretical studies on intrinsic particle migration and flow phenomena associated with inertia are being experimentally tested and validated. This collective study on the fluid-particle-structure phenomena in microchannels involving fluid inertia is called, “
inertial microfluidics
”. Beyond theoretical studies, now inertial microfluidics has been gaining much attention from various research fields ranging from biomedicine to industry. Despite the positive contributions, there is still a lack of clear understanding of intrinsic inertial effects in microchannels. Therefore, this minireview introduces the mechanisms and underlying physics in inertial microfluidic systems with specific focuses on inertial particle migration and secondary flow, and outlines the opportunities provided by inertial microfluidics, along with an outlook on the field.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hesperidin, a known flavonoid constituent of citrus, reduces the proliferation of many cancer cells. The apoptotic effects of hesperidin on human colon cancer cells, SNU-C4, were determined at ...concentrations of 1–100
μM. At 100
μM, hesperidin reduced cell viability to 65.00±0.05% of control values in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death induced by hesperidin showed apoptotic features in 4,6-diamidino-2-phenylindole (DAPI) staining and in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Examination of the expression of apoptosis-regulating genes indicated that hesperidin treatment decreased the expression of B-cell CLL/lymphoma 2 (
BCL2) mRNA, and increased the expression of BCL2-associated X protein (
BAX). The expression and activity of the major apoptotic factor caspase3 (CASP3) was increased significantly with hesperidin treatment. Hesperidin down-regulated the protein expression of pro-CASP3, and up-regulated the level of active CASP3. Thus, these results suggest that hesperidin could induce apoptosis in human colon cancer cells through CASP3 activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract We examined the joint predictive effects of childhood and adolescent onset psychiatric and substance use disorders on failure to graduate high school (HS) on time. Structured diagnostic ...interviews were conducted with a US national sample of adults (18 and over). The analysis sample included respondents with at least 8 years of education who were born in the US or arrived in the US prior to age 13 ( N = 29,662). Psychiatric disorders, substance use and substance use disorders were examined as predictors of termination or interruption of educational progress prior to HS graduation, with statistical adjustment for demographic characteristics and childhood adversities. Failure to graduate HS on time was more common among respondents with any of the psychiatric and substance use disorders examined, ranging from 18.1% (specific phobia) to 33.2% (ADHD-combined type), compared with respondents with no disorder (15.2%). After adjustment for co-occurring disorders, significant associations with failure to graduate on time remained only for conduct disorder (OR = 1.89, 95% CI 1.57–2.26) and the three ADHD subtypes (Inattentive OR = 1.78, 95% CI 1.44–2.20, Hyperactive–Impulsive OR = 1.38, 95% CI 1.14–1.67, and Combined OR = 2.06, 95% CI 1.66–2.56). Adjusting for prior disorders, tobacco use was associated with failure to graduate on time (OR = 1.97, 95% CI 1.80–2.16). Among substance users, substance use disorders were not associated with on-time graduation. The findings suggest that the adverse impact of childhood and adolescent onset psychiatric disorders on HS graduation is largely accounted for by problems of conduct and inattention. Adjusting for these disorders, smoking remains strongly associated with failure to graduate HS on time.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed ...genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.
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•GEMs enable high-throughput microrheology in unperturbed living cells•mTORC1 controls diffusion by tuning ribosome concentration•Diffusion can be accurately predicted as a function of ribosome concentration•Crowding of the cytoplasm by ribosomes increases phase separation
mTORC1 signaling controls phase transitions in the cytoplasm through its effects on molecular crowding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Harvesting the adult male Jonah crab, Cancer borealis, mainly based on the size, has become an economically significant fishery, particularly in the Southern New England region of the US since 2000. ...Many decapod crustacean fisheries including C. borealis rely on harvesting adult males. Understanding the size related-sexual maturity and the seasonal changes in male reproductive activity is critical for sustainable management. In other decapods, an insulin-like hormone produced by the male-specific androgenic gland (AG), called insulin-like androgenic gland factor (IAG), plays an essential role in sexual maturity. Specifically IAG is involved in developing male primary and secondary sexual characteristics including spermatogenesis. This study aimed first to identify the IAG, then examine if season influences IAG expression in C. borealis males. Finally, the AG transcriptome was used to test if eyestalk neuropeptides regulate IAG levels via an endocrine axis between the two endocrine tissues as established in other crustaceans. The full-length CabIAG sequence is 928 nucleotides long, encoding a 151 amino acid deduced sequence. The CabIAG identified from the AG transcriptome after eyestalk ablation was the most highly expressed gene and accounted for up to 25% of transcripts, further confirming the presence of an endocrine axis between the androgenic gland and eyestalk ganglia. This gene expression was exclusive in male C. borealis AG. The transcriptomic analysis also revealed strong upregulation of the PPOAE transcript and downregulation of proteolytic enzymes. The CabIAG levels differ by season, increasing AG activity in fall and possibly coinciding with high mating activity. The timing of increased AG activity correlating to mating with females should be considered for better stock management for the C. borealis population.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Translocator protein (TSPO; 18 kDA) is a high-affinity cholesterol-binding protein that is integrally involved in cholesterol transfer from intracellular stores into mitochondria, the ...rate-determining step in steroid formation. Previous studies have shown that TSPO drug ligands are able to activate steroid production by MA-10 mouse Leydig tumor cells and by mitochondria isolated from steroidogenic cells. We hypothesized herein that the direct, pharmacological activation of TSPO might induce aged Leydig cells, which are characterized by reduced T production, to produce significantly higher levels of T both in vitro and in vivo. To test this, we first examined the in vitro effects of the TSPO selective and structurally distinct drug ligands N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27) and benzodiazepine 4′-chlorodiazepam (Ro5-4864) on steroidogenesis by Leydig cells isolated from aged (21-24 months old) and young adult (3-6 months old) Brown Norway rats. The ligands stimulated Leydig cell T production significantly, and equivalently, in cells of both ages, an effect that was significantly inhibited by the specific TSPO inhibitor 5-androsten-3,17,19-triol (19-Atriol). Additionally, we examined the in vivo effects of administering FGIN-1-27 to young and aged rats. In both cases, serum T levels increased significantly, consistent with the in vitro results. Indeed, serum T levels in aged rats administered FGIN-1-27 were equivalent to T levels in the serum of control young rats. Taken together, these results indicate that although there are reduced amounts of TSPO in aged Leydig cells, its direct activation is able to increase T production. We suggest that this approach might serve as a therapeutic means to increase steroid levels in vivo in cases of primary hypogonadism.
•MIH and CHH full-length cDNA sequences are isolated from the eyestalk of the red deep-sea crab.•MIH and CHH neuropeptides in the sinus gland are measured.•Transcriptomic analysis of eyestalk at ...ovarian stages 1 and 3 find 28 neuropeptides.•Ten neuropeptides show their transcripts higher at ovarian stage 3 than stage 1.
Eyestalk-derived neuropeptides, primarily the crustacean hyperglycemic hormone (CHH) neuropeptide family, regulate vitellogenesis in decapod crustaceans. The red deep-sea crab, Chaceon quinquedens, a cold-water species inhabiting depths between 200 and 1800 m, has supported a small fishery, mainly harvesting adult males in the eastern US for over 40 years. This study aimed to understand the role of eyestalk-neuropeptides in vitellogenesis in C. quinquedens with an extended intermolt stage. Chromatography shows two CHH and one MIH peak in the sinus gland, with a CHH2 peak area four times larger than CHH1. The cDNA sequence of MIH and CHH of C. quinquedens is isolated from the eyestalk ganglia, and the qPCR assay shows MIH is significantly higher only at ovarian stages 3 than 4 and 5. However, MIH transcript and its neuropeptides do differ between stages 1 and 3. While CHH transcripts remain constant, its neuropeptide levels are higher at stages 3 than 1. Additionally, transcriptomic analysis of the de novo eyestalk ganglia assembly at ovarian stages 1 and 3 found 28 eyestalk neuropeptides. A GIH/VIH or GSH/VSH belonging to the CHH family is absent in the transcriptome. Transcripts per million (TPM) values of ten neuropeptides increase by 1.3 to 2.0-fold at stage 3 compared to stage 1: twofold for Bursicon α, followed by CHH, AKH/corazonin-like, Pyrokinin, CCAP, Glycoprotein B, PDH1, and IDLSRF-like peptide, and 1.3-fold of allatostatin A and short NP-F. WXXXRamide, the only downregulated neuropeptide, decreases TPM by ∼ 2-fold at stage 3, compared to stage 1. Interestingly, neuroparsin with the highest TPM values remains the same in stages 1 and 3. The mandibular organ-inhibiting hormone is not found in de novo assembly. We report that CHH, MIH, and eight other neuropeptides may play a role in vitellogenesis in this species.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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