Miracle-dz/UniFAR-FTUs huggingface dataset:
Hyperproduction of tryptophan by Escherichia coli: genetic manipulation of the pathways leading to tryptophan formation

Conversion of glucose and ammonium salts into tryptophan by mutants of Escherichia coli was examined as part of a feasibility study on the manufacture of tryptophan. This involved construction, largely by transduction, or a variety of multiple-mutation strains with defined genotypes. By comparing the properties of these strains, we were able to define in biochemical terms several changes that significantly enhance process productivity, namely (i) release of the first enzyme of the common pathway of aromatic biosynthesis and the first enzyme of the tryptophan pathway (3-deoxy-D-arabino-heptulosonate 7-phosphate synthase and the anthranilate aggregate, respectively) from inhibition by end products, (ii) blockage of the diversion of chorismate to phenylalanine and tyrosine biosynthesis, and (iii) presence of highly elevated tryptophan pathway enzyme levels, such as result from interference with both repression and attenuation, combined with gene amplification. By using strains carrying appropriate mutations to effect all of these changes, high values of specific productivity were obtained in bath culture (approximately 80 mg/g [dry weight] per h). Furthermore, a pronounced decay in the level of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase activity was implicated as a cause of declining process producitivity during stationary phase, emphasizing the value of having derepressed levels of this enzyme.
Acute Oligohydramnios: Antenatal Expression of VURD Syndrome?

Objective: Oligohydramnios (OA) is nowadays regarded as one of the best markers of renal function (RF) impairment in bladder outlet obstruction (BOO) detected in utero. As such, its onset is usually early and progressive because of decline in fetal urine production. A series of acute OA complicating pregnancies with BOO has never been reported. Methods: Over a 7-year period, 5 fetuses with in utero suspicion of BOO exhibited an abrupt decrease of amniotic fluid after the 30th week of gestation. Results: All fetuses were delivered by cesarean section: diagnosis was posterior urethral valves in 3 cases, urethral atresia in 1, and prune-belly syndrome in 1. Urologic work-up demonstrated a unilateral vesicoureteral reflux dysplasia (VURD syndrome) in all 5 fetuses. RF at 1 year was normal in 4 fetuses and impaired in 1. Conclusions: Besides obstetrical reasons, OA may also have acute onset occurring in the presence of anomalies of the urinary tract; although diagnosis is almost always BOO, functional and anatomical characteristics of the urinary tract are those of VURD syndrome with a non-functioning, refluxing renal unit. The associated acute OA/VURD syndrome may represent a milder expression of a pop-off mechanism advocated in this syndrome with a more favorable prognosis than progressive OA detected early in pregnancy.
Functional Analysis of the Cyclin-Dependent Kinase Inhibitor Pho81 Identifies a Novel Inhibitory Domain

ABSTRACT In response to phosphate limitation, Saccharomyces cerevisiae induces transcription of a set of genes important for survival. A phosphate-responsive signal transduction pathway mediates this response by controlling the activity of the transcription factor Pho4. Three components of this signal transduction pathway resemble those used to regulate the eukaryotic cell cycle: a cyclin-dependent kinase (CDK), Pho85; a cyclin, Pho80; and a CDK inhibitor (CKI), Pho81. Pho81 forms a stable complex with Pho80-Pho85 under both high- and low-phosphate conditions, but it only inhibits the kinase when cells are starved for phosphate. Pho81 contains six tandem repeats of the ankyrin consensus domain homologous to the INK4 family of mammalian CKIs. INK4 proteins inhibit kinase activity through an interaction of the ankyrin repeats and the CDK subunits. Surprisingly, we find that a region of Pho81 containing 80 amino acids C terminal to the ankyrin repeats is necessary and sufficient for Pho81's CKI function. The ankyrin repeats of Pho81 appear to have no significant role in Pho81 inhibition. Our results suggest that Pho81 inhibits Pho80-Pho85 with a novel motif.
Fractal dimensions

There are many strange sets that emerge in science. In statistical mechanics, such sets often arise at continuous phase transitions, where self-similar spatial structures arise (Chapter 12). In chaotic dynamical systems, the attractor (the set of points occupied at long times after the transients have disappeared) is often a fractal (called a strange attractor). These sets are often tenuous and jagged, with holes on all length scales, as in percolation (Fig. 1.2). We often try to characterize these strange sets by a dimension. The dimensions of two extremely different sets can be the same; the path exhibited by a random walk (embedded in three or more dimensions) is arguably a two-dimensional set, but does not locally look like a surface. However, if two sets have different spatial dimensions (measured in the same way) they are certainly qualitatively different. There is more than one way to define a dimension. Roughly speaking, strange sets are often spatially inhomogeneous, and what dimension you measure depends upon how you weight different regions of the set. In this exercise, we will calculate the information dimension (closely connected to
Fixation pattern in healthy subjects during microperimetry with the scanning laser ophthalmoscope.

BACKGROUND Visual field (VF) examinations provide important information about diagnosis and follow-up in many ocular and visual pathway disorders. Previous studies have shown that fixation stability can be measured very exactly around the center of the fixation point with SLO. The importance of measuring fixation during microperimetry in the absence of field defects is to learn more about the normal fixation pattern. This is of interest since changes in fixation pattern due to pathology can occur prior to detectable changes in the macula or visual pathway. MATERIAL/METHODS Thirty-one adult subjects with healthy eyes were recruited from the staff of the Section of Ophthalmology and Vision, Department of Clinical Neuroscience, Karolinska Institutet. The fixation pattern in one randomly selected eye from each subject was investigated with the SLO using the fixation control function in the microperimetry technique. RESULTS The results showed that the fixation pattern had a mean center of gravity located at a mean absolute distance of 0.27 degrees from the fixation point (FP) and a directional predominance of the fixation pattern was found in that the fixations were more frequently distributed vertically than horizontally. CONCLUSIONS The computerized fixation control when performing microperimetry with the SLO provides information about the fixation pattern which cannot be obtained with standard clinical perimetry techniques.
Timing of antiretroviral therapy and effects on tuberculosis treatment outcomes in HIV-co-infected patients in Malawi.

SETTING Queen Elizabeth Central Hospital, Blantyre, Malawi. OBJECTIVES To determine 1) the proportion of human immunodeficiency virus (HIV) infected tuberculosis (TB) patients started on antiretroviral therapy (ART), 2) the timing of ART and 3) the effect of the timing on TB treatment outcomes. DESIGN A retrospective record review of HIV-infected TB patients registered from January to December 2009. RESULTS A total of 3376 TB patients were registered, of whom 2665 (79%) were HIV-tested and 2042 (77%) were HIV-infected. A total of 1190 HIV-infected TB patients who were not on ART at the time of starting TB treatment were studied. Of 688 (58%) who started ART, 61% started therapy within 2 months of anti-tuberculosis treatment and 39% started later (≥2 months). Treatment success for patients with TB who started ART within 2 months was higher than for those starting ART later (RR 1.6, 95%CI 1.4-1.8), and death rates were lower (RR 0.25, 95%CI 0.19-0.35). CONCLUSION Under routine programme conditions in Malawi, a higher proportion of HIV-infected TB patients who started ART did so within 2 months of starting TB treatment, and early ART intervention was associated with better treatment outcomes. This confirms recommendations that co-infected TB patients should start ART early.
Information Transparency in B2B Auction Markets: The Role of Winner Identity Disclosure

We study the impact of information transparency in B2B auctions. Specifically, we measure the effect of concealing winners’ identities on auction outcomes using a large-scale, quasi-natural field experiment. Contrary to the conventional wisdom that “the more information, the better,” we find that concealing winners’ identities leads to a significant increase in price by approximately 6%, and such effect holds true across both online and offline channels as well as different types of bidders. We further explore the mechanism that drives the observed effect. The empirical analysis suggests that the price increase may primarily stem from the disruption of imitative bidding which relies on the identification of fellow competitors. Our findings have important implications for the design of auction markets, especially multi-channel B2B markets.
Correction for Analysis of yeast endocytic site formation and maturation through a regulatory transition point

The earliest stages of endocytic site formation and the regulation of endocytic site maturation are not well understood. Here we analyzed the order in which the earliest proteins are detectable at endocytic sites in budding yeast and found that an uncharacterized protein, Pal1p/Ydr348cp, is also present at the initial stages of endocytosis. Because Ede1p (homologue of Eps15) and clathrin are the early-arriving proteins most important for cargo uptake, their roles during the early stages of endocytosis were examined more comprehensively. Ede1p is necessary for efficient recruitment of most early-arriving proteins, but not for the recruitment of the adaptor protein Yap1802p, to endocytic sites. The early-arriving proteins , as well as the later-arriving proteins Sla2p and Ent1/2p (homologues of Hip1R and epsins), were found to have longer lifetimes in CLC1-knockout yeast, which indicates that clathrin light chain facilitates the transition from the intermediate to late coat stages. Cargo also arrives during the early stages of endocytosis, and therefore its effect on endocytic machinery dynamics was investigated. Our results are consistent with a role for cargo in regulating the transition of endocytic sites from the early stages of formation to the late stages during which vesicle formation occurs.
Preventing cognitive decline in sickle cell disease

Among children with sickle cell disease (SCD), 40% of untreated children with elevated transcranial Doppler (TCD) velocities will develop stroke within 3 years.1 In 1998, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) demonstrated that the use of chronic red blood cell transfusions in children with SCD with elevated TCD velocities in the middle cerebral artery decreased the risk of stroke by 92%. 2 STOP, which revolutionized the outlook of children with SCD, relied on the assumption that TCD velocity predicts the risk for developing stenosing arteriopathy prior to the development of irreversible arteriopathy. Cerebral arteriopathy is a potent risk factor for primary and recurrent stroke in childhood, including among children with SCD.3,4
Effect of Highly Active Antiretroviral Therapy on Homocysteine Plasma Concentrations in HIV-1–Infected Patients

Objective:To analyze the effect of antiretroviral therapy on homocysteine levels in HIV-1-infected patients. Design:Observational, prospective study of patients with AIDS. Methods:We included patients with HIV-1 infection naive for antiretroviral drugs. Before and after 6 months of treatment, we evaluated fasting and postoral methionine load plasma homocysteine, serum vitamins B6 and B12, and intraerythrocyte folate levels. Results:We studied 69 patients who began therapy for a 6-month period. Fasting and postoral methionine load plasma homocysteine levels increased significantly after 6 months of antiretroviral therapy with respect to basal values (P < 0.001). Fasting hyperhomocysteinemia was present in 7.3% of patients before treatment and in 89.9% after 6 months of therapy (P = 0.0001). Postoral methionine load hyperhomocysteinemia was found in 4.5% of subjects before therapy vs. 98.5% at the end of study period (P = 0.001). These results were not associated with folate or vitamins B6 or B12 levels. Conclusions:In patients with HIV-1 infection, fasting and postoral methionine load plasma homocysteine levels increased after 6 months of antiretroviral treatment. Nutritional abnormalities were not responsible for hyperhomocysteinemia, suggesting that enzymatic disturbances in the metabolic pathways of homocysteine may occur.
Deaf Children Creating Written Texts: Contributions of American Sign Language and Signed Forms of English

The objectives of this descriptive study were to investigate the ways in which American Sign Language (ASL) and English-based sign allow for comprehension of text content, and to determine how these two avenues of communication might mediate the process of reconstructing "signed meaning" in a written text. The authors argue that comprehensible input in a visual mode is possible in either ASL or English-based sign. They further claim that English-based signing may be an effective means of bridging the gap between inner speech and written text.
A phospholipid-deacylating system of bacteria active in a frozen medium.

A phosphatidylcholine-deacylating system present in a Butyrivibrio species (probably fibrisolvens) shows appreciable activity at low temperatures with a maximum hydrolysis rate at--10 degrees C. 2. The rate at--10 degrees C is higher than at 39 degrees C unless the system at the latter temperature is stimulated by adding oleic acid or sodium dodecyl sulphate. 3. The low-temperature phospholipase activity has an absolute requirement for thiol reagents, e.g. cysteine, dithiothreitol or mercaptoethanol. 4. Ca2+, Mg2+ and Mn2+ stimulate the activity up to 10 mM, but EDTA inhibits; higher concentrations of Ca2+ also inhibit. 5. The enhancement of activity at low temperatures appears not to be associated with a crystalline change in the hydrated phospholipid substrate, but depends on the formation of a solid phase in the incubation medium which brings the substrate and bacterial cells into juxtaposition or causes fusion.
THE NEXT GENERATION VIRGO CLUSTER SURVEY. VII. THE INTRINSIC SHAPES OF LOW-LUMINOSITY GALAXIES IN THE CORE OF THE VIRGO CLUSTER, AND A COMPARISON WITH THE LOCAL GROUP

We investigate the intrinsic shapes of low-luminosity galaxies in the central 300 kpc of the Virgo Cluster using deep imaging obtained as part of the Next Generation Virgo Cluster Survey (NGVS). We build a sample of nearly 300 red-sequence cluster members in the yet-unexplored −14 < Mg < −8 mag range, and we measure their apparent axis ratios, q, through Sérsic fits to their two-dimensional light distribution, which is well described by a constant ellipticity parameter. The resulting distribution of apparent axis ratios is then fit by families of triaxial models with normally distributed intrinsic ellipticities, E = 1 − C/A, and triaxialities, T = (A2 − B2)/(A2 − C2). We develop a Bayesian framework to explore the posterior distribution of the model parameters, which allows us to work directly on discrete data, and to account for individual, surface-brightness-dependent axis ratio uncertainties. For this population we infer a mean intrinsic ellipticity E ¯ ? > = 0.43 - 0.02 + 0.02 ? > and a mean triaxiality T ¯ ? > = 0.16 - 0.06 + 0.07 ? > . This implies that faint Virgo galaxies are best described as a family of thick, nearly oblate spheroids with mean intrinsic axis ratios 1:0.94:0.57. The core of Virgo lacks highly elongated low-luminosity galaxies, with 95% of the population having q > 0.45. We additionally attempt a study of the intrinsic shapes of Local Group (LG) satellites of similar luminosities. For the LG population we infer a slightly larger mean intrinsic ellipticity E ¯ ? > = 0.51 - 0.06 + 0.07 ? > , and the paucity of objects with round apparent shapes translates into more triaxial mean shapes, 1:0.76:0.49. Numerical studies that follow the tidal evolution of satellites within LG-sized halos are in good agreement with the inferred shape distributions, but the mismatch for faint galaxies in Virgo highlights the need for more adequate simulations of this population in the cluster environment. We finally compare the intrinsic shapes of NGVS low-mass galaxies with samples of more massive quiescent systems, and with field, star-forming galaxies of similar luminosities. We find that the intrinsic flattening in this low-luminosity regime is almost independent of the environment in which the galaxy resides, but there is a hint that objects may be slightly rounder in denser environments. The comparable flattening distributions of low-luminosity galaxies that have experienced very different degrees of environmental effects suggest that internal processes are the main drivers of galaxy structure at low masses, with external mechanisms playing a secondary role.
Bromodomain and Extraterminal (BET) Protein Inhibition Suppresses Human T Cell Leukemia Virus 1 (HTLV-1) Tax Protein-mediated Tumorigenesis by Inhibiting Nuclear Factor κB (NF-κB) Signaling*

Background: The HTLV-1 oncoprotein Tax induces sustained NF-κB activation for cell survival and proliferation gene expression. Results: Recruitment of Brd4 to acetylated RelA is essential for Tax-mediated NF-κB target gene expression and cell proliferation. Conclusion: Blocking the binding of Brd4 to acetylated RelA by JQ1 suppresses Tax-mediated NF-κB activation and tumorigenesis. Significance: Inhibiting Brd4 could be a potential therapeutic strategy for diseases associated with HTLV-1 infection. The etiology of human T cell leukemia virus 1 (HTLV-1)-mediated adult T cell leukemia is associated with the ability of viral oncoprotein Tax to induce sustained NF-κB activation and the expression of many NF-κB target genes. Acetylation of the RelA subunit of NF-κB and the subsequent recruitment of bromodomain-containing factor Brd4 are important for the expression of NF-κB target genes in response to various stimuli. However, their contributions to Tax-mediated NF-κB target gene expression and tumorigenesis remain unclear. Here we report that Tax induced the acetylation of lysine 310 of RelA and the binding of Brd4 to acetylated RelA to facilitate Tax-mediated transcriptional activation of NF-κB. Depletion of Brd4 down-regulated Tax-mediated NF-κB target gene expression and cell proliferation. Inhibiting the interaction of Brd4 and acetylated RelA with the bromodomain extraterminal protein inhibitor JQ1 suppressed the proliferation of Tax-expressing rat fibroblasts and Tax-positive HTLV-1-infected cells and Tax-mediated cell transformation and tumorigenesis. Moreover, JQ1 attenuated the Tax-mediated transcriptional activation of NF-κB, triggering the polyubiquitination and proteasome-mediated degradation of constitutively active nuclear RelA. Our results identify Brd4 as a key regulator for Tax-mediated NF-κB gene expression and suggest that targeting epigenetic regulators such as Brd4 with the bromodomain extraterminal protein inhibitor might be a potential therapeutic strategy for cancers and other diseases associated with HTLV-1 infection.
New distribution record of Elysia leucolegnote (Jensen, 1990) (Sacoglossa Plakobranchidae) in mangrove ecosystem of Biak Numfor, Papua - Indonesia

Received 29.10. 2019; accepted 21.02. 2020; published online 20.03. 2020 Elysia leucolegnote (Jensen, 1990) (Sacoglossa Plakobranchidae) was firstly found in Hong Kong and described in 1989. Furthermore, in the past decade, the mangrove leaf-slug, E. leucolegnote, has been found outside Hong Kong, for example in Thailand, India, and Australia, but it is here reported for the first time in Indonesia. Details on the distribution, habitat and external morphology of E. leucolegnote in Biak Numfor, Papua, Indonesia, are here described. This species is found in mangrove ecosystems and has a similar morphological external character with previously reported which are distributed worldwide from East, South and Southeast Asia to Australia. The IUCN redlist category is discussed in this paper.
Ubiquitination of Free Cyclin D1 Is Independent of Phosphorylation on Threonine 286*

Cyclin D1 binds and regulates the activity of cyclin-dependent kinases (CDKs) 4 and 6. Phosphorylation of the retinoblastoma protein by cyclin D1·CDK4/6 complexes during the G1 phase of the cell cycle promotes entry into S phase. Cyclin D1 protein is ubiquitinated and degraded by the 26 S proteasome. Previous studies have demonstrated that cyclin D1 ubiquitination is dependent on its phosphorylation by glycogen synthase kinase 3β (GSK-3β) on threonine 286 and that this phosphorylation event is greatly enhanced by binding to CDK4 (Diehl, J. A., Cheng, M. G., Roussel, M. F., and Sherr, C. J. (1998) Genes Dev. 12, 3499–3511). We now report an additional pathway for the ubiquitination of free cyclin D1 (unbound to CDKs). We show that, when unbound to CDK4, a cyclin D1-T286A mutant is ubiquitinated. Further, we show that a mutant of cyclin D1 that cannot bind to CDK4 (cyclin D1-KE) is also ubiquitinated in vivo. Our results demonstrate that free cyclin D1 is ubiquitinated independently of its phosphorylation on threonine 286 by GSK-3β, suggesting that, as has been shown for cyclin E, distinct pathways of ubiquitination lead to the degradation of free and CDK-bound cyclin D1. The pathway responsible for ubiquitination of free cyclin D1 may be important in limiting the effects of cyclin D1 overexpression in a variety of cancers.
Comprehensive screening of multiple epiphyseal dysplasia mutations in Japanese population

Multiple epiphyseal dysplasia (MED) is among the most genetically heterogeneous skeletal dysplasias. Six genes involved in MED, COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST have been identified; however, the presence of additional disease genes has been reported, and the detection rate for mutations in known genes accounts for no more than 50% of patients with MED in Western populations. Here, we screened the six known disease genes in 35 consecutive Japanese MED patients. We analyzed the entire coding region of each gene, along with flanking intron–exon junctions, by direct sequencing. A total of 19 mutations were identified in COMP, MATN3, COL9A2, COL9A3, and DTDST. The detection rate for known mutations was higher in this study than in previous reports, and we identified a substantially different spectrum of mutations. Mutations in MATN3 were more prevalent among these Japanese patients, whereas no DTDST mutations were detected. Most of the mutations were localized within specific regions of each gene: COMP mutations were found in the calmodulin‐like repeat domains; MATN3 mutations in the von Willebrand factor type A domain; and type IX collagen gene mutations occurred in the third collagenous domains. Based on the integration of clinical and genetic information, we propose an algorithm for detecting mutations in Japanese MED patients. Our study further supports the existence of additional MED gene(s). © 2006 Wiley‐Liss, Inc.