Miracle-dz/UniFAR-FTUs huggingface dataset:
Human 1-Acylglycerol-3-phosphate O-Acyltransferase Isoforms 1 and 2

Loss-of-function mutations in 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) 2 in humans and mice result in loss of both the white and brown adipose tissues from birth. AGPAT2 generates precursors for the synthesis of glycerophospholipids and triacylglycerols. Loss of adipose tissue, or lipodystrophy, results in hyperinsulinemia, diabetes mellitus, and severe hepatic steatosis. Here, we analyzed biochemical properties of human AGPAT2 and its close homolog, AGPAT1, and we studied their role in liver by transducing their expression via recombinant adenoviruses in Agpat2−/− mice. The in vitro substrate specificities of AGPAT1 and AGPAT2 are quite similar for lysophosphatidic acid and acyl-CoA. Protein homology modeling of both the AGPATs with glycerol-3-phosphate acyltransferase 1 (GPAT1) revealed that they have similar tertiary protein structure, which is consistent with their similar substrate specificities. When co-expressed, both isoforms co-localize to the endoplasmic reticulum. Despite such similarities, restoring AGPAT activity in liver by overexpression of either AGPAT1 or AGPAT2 in Agpat2−/− mice failed to ameliorate the hepatic steatosis. From these studies, we suggest that the role of AGPAT1 or AGPAT2 in liver lipogenesis is minimal and that accumulation of liver fat is primarily a consequence of insulin resistance and loss of adipose tissue in Agpat2−/− mice.
Roles for phagocytic cells and complement in controlling relapsing fever infection

Relapsing fever spirochetes, such as Borrelia hermsii, proliferate to high levels in their hosts’ bloodstream until production of IgM against borrelial surface proteins promotes bacterial clearance. The mechanisms by which B. hermsii survives in host blood, as well as the immune mediators that control this infection, remain largely unknown. It has been hypothesized that B. hermsii is naturally resistant to killing by the alternative pathway of complement activation as a result of its ability to bind factor H, a host complement regulator. However, we found that Cfh−/− mice were infected to levels identical to those seen in wild‐type mice. Moreover, only a small minority of B. hermsii in the blood of wild‐type mice had detectable levels of factor H adhered to their outer surfaces. In vitro, complement was found to play a statistically significant role in antibody‐mediated inactivation of B. hermsii, although in vivo studies indicated that complement is not essential for host control of B. hermsii. Depletion of mφ and DC from mice had significant impacts on B. hermsii infection, and depleted mice were unable to control bloodstream infections, leading to death. Infection studies using muMT indicated a significant antibody‐independent role for mφ and/or DC in host control of relapsing fever infection. Together, these findings indicate mφ and/or DC play a critical role in the production of B. hermsii‐specific IgM and for antibody‐independent control of spirochete levels.
Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) represents one of the most common genetic causes of epilepsy. TSC gene inactivation leads to hyperactivation of the mammalian target of rapamycin signaling pathway, raising the intriguing possibility that mammalian target of rapamycin inhibitors might be effective in preventing or treating epilepsy in patients with TSC. Mice with conditional inactivation of the Tsc1 gene primarily in glia (Tsc1GFAPCKO mice) develop glial proliferation, progressive epilepsy, and premature death. Here, we tested whether rapamycin could prevent or reverse epilepsy, as well as other cellular and molecular brain abnormalities in Tsc1GFAPCKO mice.
Effect of m-3M3FBS on Ca2+ movement in Madin-Darby canine renal tubular cells

The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C (PLC) activator, on cytosolic free Ca2+ concentrations ([Ca 2+]i) in Madin-Darby canine kidney (MDCK) cells is unclear. This study explored whether m-3M3FBS changed basal [Ca2+]i levels in suspended MDCK cells using fura-2 as a Ca2+-sensitive fluorescent dye. M-3M3FBS at concentrations between 0.1 and 20 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was decreased by removing extracellular Ca2+. M-3M3FBS-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca2+-free medium, 20-μM m-3M3FBS pretreatment abolished the [Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin (TG) and cyclopiazonic acid (CPA). Conversely, pretreatment with TG or CPA partly reduced m-3M3FBS-induced [Ca2+]i rise. The inhibition of PLC with U73122 did not alter m-3M3FBS-induced [Ca2+]i rise. Collectively, in MDCK cells, m-3M3FBS induced [Ca2+]i rises by causing PLC-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store-operated Ca2+ channels and other unidentified Ca2+ channels.
Translocation of Yersinia enterocolitica across reconstituted intestinal epithelial monolayers is triggered by Yersinia invasin binding to β1 integrins apically expressed on M‐like cells

Yersinia enterocolitica cross the intestinal epithelium via translocation through M cells, which are located in the follicle‐associated epithelium (FAE) of Peyer's patches (PP). To investigate the molecular basis of this process, studies were performed using a recently developed in vitro model, in which the enterocyte‐like cell line Caco‐2 and PP lymphocytes are co‐cultured in order to establish FAE‐like structures including M cells. Here, we demonstrate that Y. enterocolitica does not adhere significantly to the apical membrane of differentiated enterocyte‐like Caco‐2 cells that express binding sites for Ulex europaeus agglutinin (UEA)‐1. In contrast, Y. enterocolitica adhered to, and was internalized by, cells that lacked UEA‐1 binding sites and displayed a disorganized brush border. These cells were considered to be converted to M‐like cells. Further analysis revealed that part of these cells expressed β1 integrins at their apical surface and, as revealed by comparison of wild‐type and mutant strains, interacted with invasin of Y. enterocolitica. Consistently, anti‐β1 integrin antibodies significantly inhibited internalization of inv‐expressing yersiniae. Experiments with Yersinia mutant strains deficient in YadA or Yop secretion revealed that these virulence factors play a minor role in this process. After internalization, yersiniae were transported within LAMP‐1‐negative vacuoles to, and released at, the basal surface. Internalization and transport of yersiniae was inhibited by cytochalasin D, suggesting that F‐actin assembly is required for this process. These results provide direct evidence that expression of β1 integrins at the apical surface of M cells enables interaction with the invasin of Y. enterocolitica, and thereby initiates internalization and translocation of bacteria.
Interleukin-10 functions as an antiinflammatory cytokine in rheumatoid synovium.

OBJECTIVE Interleukin-10 (IL-10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We therefore investigated the effects of IL-10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA. In addition, we studied the production of IL-10 in rheumatoid joints, and the role of endogenous IL-10 in the regulation of SFMC function. METHODS The presence of IL-10 in rheumatoid joints was studied using IL-10-specific enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase- polymerase chain reaction (RT-PCR) techniques. The effects of recombinant human IL-10 or neutralizing anti-IL-10 monoclonal antibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry. The effect of IL-10 on proliferation of SFMC was determined by incorporation of tritiated thymidine. RESULTS IL-10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL-10 messenger RNA was detectable in all 8 SFMC samples, as determined by RT-PCR. Neutralization of endogenously produced IL-10 by anti- IL-10 MAbs resulted in increased production of IL-1 beta, tumor necrosis factor alpha (TNF alpha), and granulocyte- macrophage colony-stimulating factor (GM-CSF) by SFMC, and in enhanced proliferation of SFMC. In particular, the production of TNFalpha was dramatically increased by anti-IL-10 MAbs. Moreover, the expression of HLA-DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti-IL-10 MAbs. In contrast, addition of recombinant IL-10 significantly decreased the production of IL-1 beta, TNF alpha, and GM-CSF by SFMC, and decreased spontaneous and IL-2-induced proliferation of SFMC. Finally, IL-10 decreased HLA-DR expression and increased the expression of the Fc gamma receptors, CD16 and CD64, by SF macrophages. CONCLUSION These data indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.
Critical Appraisal of Indices for the Assessment of Baroreflex Sensitivity

Abstract: The sequence technique and the spectral estimation of the alpha coefficient are currently employed for the assessment of “spontaneous” baroreflex sensitivity (BRS). The comparison of performance and effectiveness of these techniques is obtained by the analysis of systolic blood pressure (SBP) and pulse interval (PI) tracings recorded in conscious cats before and after baroreceptor denervation. Results indicate that (1) the average BRS estimates obtained by the sequence technique and by the alpha coefficient at the respiratory frequency are similar, (2) the alpha coefficients computed at the respiratory frequency tend to be higher than alpha coefficients estimated at 0.1 Hz, and (3) in spite of what is traditionally claimed, the PI-SBP coherence does not seem to represent a reliable parameter to enhance the specificity of the spectral estimate, because coherence values often remain above the 0.5 threshold also after baroreceptor denervation.
Unusual evolutionary history of the tRNA splicing endonuclease EndA: Relationship to the LAGLIDADG and PD‐(D/E)XK deoxyribonucleases

The tRNA splicing endoribonuclease EndA from Methanococcus jannaschii is a homotetramer formed via heterologous interaction between the two pairs of homodimers. Each monomer consists of two α/β domains, the N‐terminal domain (NTD) and the C‐terminal domain (CTD) containing the RNase A‐like active site. Comparison of the EndA coordinates with the publicly available protein structure database revealed the similarity of both domains to site‐specific deoxyribonucleases: the NTD to the LAGLIDADG family and the CTD to the PD‐(D/E)XK family. Superposition of the NTD on the catalytic domain of LAGLIDADG homing endonucleases allowed a suggestion to be made about which amino acid residues of the tRNA splicing nuclease might participate in formation of a presumptive cryptic deoxyribonuclease active site. On the other hand, the CTD and PD‐(D/E)XK endonucleases, represented by restriction enzymes and a phage λ exonuclease, were shown to share extensive similarities of the structural framework, to which entirely different active sites might be attached in two alternative locations. These findings suggest that EndA evolved from a fusion protein with at least two distinct endonuclease activities: the ribonuclease, which made it an essential “antitoxin” for the cells whose RNA genes were interrupted by introns, and the deoxyribonuclease, which provided the means for homing‐like mobility. The residues of the noncatalytic CTDs from the positions corresponding to the catalytic side chains in PD‐(D/E)XK deoxyribonucleases map to the surface at the opposite side to the tRNA binding site, for which no function has been implicated. Many restriction enzymes from the PD‐(D/E)XK superfamily might have the potential to maintain an additional active or binding site at the face opposite the deoxyribonuclease active site, a property that can be utilized in protein engineering.
Image-based motion estimation of underwater tow body

During deep sea exploration, the motion of the deep tow system is influenced by that of the surface vessel, the change of the cable length and the current field in the water column. Though the towing vessel moves in a straight line on the sea surface, the heading of the tow body is not necessary collinear to the towing direction. If no devices are available to adjust the direction of the tow body, data collected by directional sensors, like camera or side scan sonar, will be skewed. It causes problems and difficulties in the post processing for mosaicing data sets into a map of a larger area. Moreover, the existence of the offset angle creates a staircase-like pattern on the map when the images are stitched together. The staircase pattern hampers the continuity of the data. The offset angle, in theory, can be computed from the USBL and the compass readings. But in practice, the refresh rates of USBL and the compass are not compatible such that the results are not good enough for maneuvering the tow system. In this paper, we propose using the feature points on the images acquired to estimate the offset angle of the tow system with respect to the trace of the motion. The computation is carried out with the OPENCV library implemented in Visual C. Currently, the refresh rate can be about 2 Hz with 30 fps camera acquisition, given the tow body is moving with 0.5 m/s speed.
Area‐wide impact of macrocyclic lactone parasiticides in cattle dung

Following the treatment of cattle with veterinary parasiticides and insecticides, residues are excreted into the dung in concentrations that may be toxic to functionally important dung‐colonizing insects. In the dung, these residues cause a range of well‐studied lethal and sub‐lethal effects, the magnitudes of which vary with the compound used, mode of administration and concentration, and the insect species in question. Particular concern has been associated with the use of macrocyclic lactones in this context. Loss of insect colonizers may delay pat decomposition, but field studies report contrasting results that reflect confounding factors such as weather conditions, pat moisture content, pat location, time of year and dung insect species phenologies. The question of fundamental concern is whether the impacts seen in experimental or laboratory studies are likely to have a functional impact on insect populations, community interactions and the economically important process of dung decomposition. Recent studies which have attempted to address these wider, landscape‐level impacts in temperate ecosystems are reviewed here. These show that the extent to which chemical residues may have any sustained ecological impact will depend on both a range of farm management factors, such as the temporal and spatial patterns of chemical use, the number of animals treated and the choice of active ingredient, and a range of insect‐related factors, such as abundance, population dynamics and dispersal rates. However, they also demonstrate that considerable uncertainty remains about the likely extent of such effects and that current data are insufficient to support firm conclusions regarding sustained pasture‐level effects. More large‐scale, longterm field experiments are required, particularly in relation to insect dispersal and functional interactions within the dung insect community.
Tranexamic Acid Prophylaxis in Hip and Knee Joint Replacement.

BACKGROUND The antifibrinolytic agent tranexamic acid (TXA) is widely used for the prevention and treatment of hyperfibrinolytic states, such as in severe polytrauma. It can also be used for the systemic prevention of hemorrhage in elective orthopedic procedures. In this review, we assess the efficacy and risks of the prophylactic administration of tranexamic acid before major endoprosthetic surgery of the hip and knee. METHODS This review is based on pertinent articles retrieved by a selective literature search in the PubMed and Cochrane Library databases. RESULTS Endoprosthetic surgery of the hip and knee is often associated with perioperative blood losses exceeding 500 mL. The prophylactic administration of tranexamic acid immediately before such procedures has been shown in randomized, controlled trials to lessen the quantity of intra- and postoperative bleeding and to reduce the likelihood of blood transfusion (number needed to treat [NNT] 3.7-5.7 for knee replacement and 4.1-8.2 for hip replacement). The rate of thromboembolic events did not differ significantly from the rate in the placebo groups. No reliable data are available on the frequency of epileptic seizures as a complication of TXA use in knee and hip endoprosthetic surgery. On the basis of data from other types of surgery, one may reasonably conclude that the doses of TXA used for knee and hip endoprosthetic procedures are unlikely to cause this problem. CONCLUSION The prophylactic intravenous administration of tranexamic acid lessens the amount of bleeding in endoprosthetic knee and hip procedures and reduces the likelihood of blood transfusion. According to the current state of the evidence, complications are rare. Nonetheless, consideration of the risks and benefits implies that tranexamic acid should not be given for this purpose to patients who have recently had urogenital bleeding, pulmonary embolism, or a myocardial infarction, who have recently undergone percutaneous transluminal coronary angioplasty or stenting, or who are known to have epilepsy.
Design of a variable-stiffness flapping mechanism for maximizing the thrust of a bio-inspired underwater robot

Compliance can increase the thrust generated by the fin of a bio-inspired underwater vehicle. To improve the performance of a compliant fin, the compliance should change with the operating conditions; a fin should become stiffer as the oscillating frequency increases. This paper presents a novel variable-stiffness flapping (VaSF) mechanism that can change its stiffness to maximize the thrust of a bio-inspired underwater robot. The mechanism is designed on the basis of an endoskeleton structure, composed of compliant and rigid segments alternately connected in series. To determine the attachment point of tendons, the anatomy of a dolphin's fluke is considered. Two tendons run through the mechanism to adjust the stiffness. The fluke becomes stiffer when the tendons are pulled to compress the structure. The thrust generated by a prototype mechanism is measured under different conditions to show that the thrust can be maximized by changing the stiffness. The thrust of the VaSF device can approximately triple at a certain frequency just by changing the stiffness. This VaSF mechanism can be used to improve the efficiency of a bio-inspired underwater robot that uses compliance.
Does Unilateral Oocyte Retrieval due to Transvaginally Inaccessible Ovaries, Contrary to Common Beliefs, Affect IVF/ICSI Treatment Outcomes That Much?

Objective. To investigate in vitro fertilization (IVF) treatment outcomes of unilateral oocyte retrieval in patients with transvaginally inaccessible ovaries. Study Design. Ninety-two women who underwent unilateral oocyte retrieval were retrospectively matched for age, antral follicle count, and body mass index with 184 women who underwent bilateral oocyte retrieval. Each patient in bilateral oocyte retrieval group had the same number of cumulus oophorus complexes (COCs) from single ovary and had comparable number of follicles (±2) on contralateral site where follicular aspiration was performed. Results. The number of COCs, metaphase-2 oocytes, 2-pronuclei, and top-quality embryos was significantly lower in unilateral oocyte retrieval group. However, proportion of patients with an embryo transfer of at least one top-quality embryo was found to be comparable between unilateral and bilateral oocyte retrieval. Subsequently, clinical pregnancy and live birth rates were found to be similar between the groups. The ROC curve analysis revealed (AUC = 0.74, 95% CI 0.63–0.86, p = 0.001) that retrieved COCs ≥ 5 from single ovary had sensitivity of 76.0% and specificity of 64.2% for occurrence of a clinical pregnancy. Conclusion. The patients with unilateral oocyte retrieval have reasonable chance of success with IVF. The retrieval of ≥5 COCs from accessible ovary might result in better treatment outcomes among these patients.
Experimental Varicocele Induces p53-Dependent Germ Cell Apoptosis through Activation of γ-H2AX

Aim: Since DNA damage-related apoptosis is raising concerns regarding abnormal spermatogenesis, we investigated the changes in γ-H2AX during testicular germ cell apoptotic responses in the varicocele model. Materials and Methods: Varicocele was induced by partial ligation of the left renal vein and animals were sacrificed at 1, 3, and 4 weeks after varicocele creation. The levels of activated p53 and γ-H2AX formation were determined by Western blot analysis and immunohistochemistry. Results: γ-H2AX formation was augmented after varicocele creation, while a significant increase in p53 phosphorylation was detected in a time course-dependent manner. Varicocele-dependent nuclear γ-H2AX staining in the primary spermatocytes was prominent as degenerative foci, while little differences could be detected in spermatogonia. Conclusions: These results show that experimental varicocele may induce p53-dependent apoptosis through activation of γ-H2AX in the primary spermatocytes, and suggest that γ-H2AX may be related to apoptotic signal transduction in experimental varicocele.
Mouse fertility is enhanced by oocyte‐specific loss of core 1‐derived O‐glycans

Regulation of the number of eggs ovulated by different mammalian species remains poorly understood. Here we show that oocyte‐specific deletion at the primary follicle stage of core 1 β 1,3‐galactosyl‐transferase (T‐synthase;generates core 1‐derived O‐glycans), leads to a sustained increase in fertility. T‐syn mutant females ovulated 30–50% more eggs and had a sustained increase in litter size compared to controls. Ovarian weights and follicle numbers were greater in mutants, but follicular apoptosis was not decreased. The number of follicles entering the growing pool was unaltered, but 3‐wk mutants ovulated fewer eggs, suggesting that increased fertility results from prolonged follicle development. T‐syn mutant ovaries also contained numerous multiple‐oocyte follicles (MOFs) that appeared to form by adjacent, predominantly preantral, follicles joining — a new mechanism for MOF generation. Ovulation of multiple eggs from MOFs was not the reason for increased fertility based on ovulated egg and corpora lutea numbers. Thus, the absence of T‐synthase caused modified follicular development, leading to the maturation and ovulation of more follicles, to MOF formation at late stages of folliculogenesis, and to increased fertility. These results identify novel roles for glycoproteins from the oocyte as suppressors of fertility and regulators of follicular integrity in the mouse. —Williams, S. A. , Stanley, P. Mouse fertility is enhanced by oocyte‐specific loss of core 1‐ derived O‐glycans. FASEB J. 22, 2273–2284 (2008)