Miracle-dz/UniFAR-FTUs huggingface dataset:
Tom20 Mediates Localization of mRNAs to Mitochondria in a Translation-Dependent Manner

ABSTRACT mRNAs encoding mitochondrial proteins are enriched in the vicinity of mitochondria, presumably to facilitate protein transport. A possible mechanism for enrichment may involve interaction of the translocase of the mitochondrial outer membrane (TOM) complex with the precursor protein while it is translated, thereby leading to association of polysomal mRNAs with mitochondria. To test this hypothesis, we isolated mitochondrial fractions from yeast cells lacking the major import receptor, Tom20, and compared their mRNA repertoire to that of wild-type cells by DNA microarrays. Most mRNAs encoding mitochondrial proteins were less associated with mitochondria, yet the extent of decrease varied among genes. Analysis of several mRNAs revealed that optimal association of Tom20 target mRNAs requires both translating ribosomes and features within the encoded mitochondrial targeting signal. Recently, Puf3p was implicated in the association of mRNAs with mitochondria through interaction with untranslated regions. We therefore constructed a tom20Δ puf3Δ double-knockout strain, which demonstrated growth defects under conditions where fully functional mitochondria are required. Mislocalization effects for few tested mRNAs appeared stronger in the double knockout than in the tom20Δ strain. Taken together, our data reveal a large-scale mRNA association mode that involves interaction of Tom20p with the translated mitochondrial targeting sequence and may be assisted by Puf3p.
The syndromes of frontotemporal dysfunction in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is increasingly recognized to be a complex multisystems disorder both at the level of its pathobiology and in the breadth of non-motor manifestations that can accompany it. Paramount among these are disorders of frontotemporal function which can be associated with syndromes of behavioural, cognitive or executive dysfunction or manifest as a frontotemporal dementia (FTD). While these may occur in isolation and precede the development of motor deficits, more commonly they insidiously onset following the initial neuromuscular dysfunction. The earliest clinical manifestation is a loss of verbal fluency, disproportionate to impairments in oromotor control. There is good correlation between the presence of a syndrome of frontotemporal dysfunction and alterations in brain structure or function as identified with a wide variety of neuroimaging techniques and which reflect a frontotemporal lobar degeneration (FTLD). Although the cause(s) of this process remain to be defined, as with the clinical heterogeneity, there is likely to be significant biochemical heterogeneity. This includes alterations in tau protein metabolism which are present in a proportion of familial and sporadic ALS cases, as well as the western Pacific variant, and recently described alterations in the metabolism of the TAR DNA binding protein 43 (TDP-43).
Localization of Banana bunchy top virus and cellular compartments in gut and salivary gland tissues of the aphid vector Pentalonia nigronervosa

Banana bunchy top virus (BBTV) (Nanoviridae: Babuvirus) is transmitted by aphids of the genus Pentalonia in a circulative manner. The cellular mechanisms by which BBTV translocates from the anterior midgut to the salivary gland epithelial tissues are not understood. Here, we used multiple fluorescent markers to study the distribution and the cellular localization of early and late endosomes, macropinosomes, lysosomes, microtubules, actin filaments, and lipid raft subdomains in the gut and principal salivary glands of Pentalonia nigronervosa. We applied colabeling assays, to colocalize BBTV viral particles with these cellular compartments and structures. Our results suggest that multiple potential cellular processes, including clathrin‐ and caveolae‐mediated endocytosis and lipid rafts, may not be involved in BBTV internalization.
Cancer patients' experience of positive and negative changes due to the illness: relationships with psychological well‐being, coping, and goal reengagement

Objective: Most studies in cancer patients on psychological changes focused on positive changes (so‐called ‘posttraumatic growth’), with surprisingly little attention on the possibility that patients may experience both positive and negative changes. This study investigated the relationship between positive and negative changes, and their association with positive and negative affect. We also examined the correlates of positive and negative changes, specifically the role of coping and goal reengagement.
Prevalence and risk factors of epiretinal membrane in Asian Indians.

PURPOSE To describe the prevalence of epiretinal membrane (ERM) and its risk factors in an Indian population and compare the findings with other populations. METHODS The Singapore Indian Eye Study is a population-based survey of 3400 Asian Indians aged between 40 and 80 years. A comprehensive ophthalmic examination, standardized interviews, and laboratory blood tests were performed. Digital retinal fundus photographs were assessed for the presence of ERM following the definitions used in the Blue Mountains Eye Study (BMES). ERM was classified into a less severe form termed "cellophane macular reflex" (CMR) and a more severe form termed "preretinal macular fibrosis" (PMF) and also as primary and secondary (if it was associated with retinal pathology or cataract surgery). RESULTS A total of 3328 persons (mean age 57.8 ± [SD] 10.1 years, and 50.2% male) provided data in this study. The age-standardized prevalence of ERM was 7.6% (95% confidence interval [CI], 6.8-8.6), CMR 4.1% (95% CI, 3.5-4.9), and PMF 3.5% (95% CI, 2.9-4.2). Older age (odds ratio [OR], 1.09; 95% CI, 1.07-1.11, per year increase), increasing myopic refraction (OR, 1.14; 95% CI, 1.07-1.22, per diopter decrease), and narrower retinal arteriolar diameter (OR, 1.02; 95% CI, 1.00-1.03, per μm decrease) were significantly associated with primary ERM. CONCLUSIONS The age-standardized prevalence of ERM in the Indian population in Singapore was 7.6%. This is similar to Malays in Singapore (8.0%) and higher than the prevalence in whites in Australia (4.7%). Significant factors associated with primary ERM were older age, myopia, and narrower retinal arteriolar diameter.
Schwann cells, neurotrophic factors, and peripheral nerve regeneration

The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), neurotrophin‐4/5 (NT‐4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)‐β and their distant relative, glial cell line–derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors. © 1998 Wiley‐Liss, Inc. MICROSURGERY 18:397–405, 1998
Metaheuristics for Lexicographic Optimization in Industry

In this paper, we highlight the legitimacy of adopting a lexicographic optimization framework for multi-objective problems arising in various industrial contexts such as production, transportation, telecommunication, and supply chain management. We describe the main ingredients of the metaheuristics that are successfully applied to these diverse practical situations.
Microcosm wetlands for wastewater treatment with different hydraulic loading rates and macrophytes.

Constructed wetlands (CW) usually require large land areas for treating wastewater. This study evaluated the feasibility of applying CW with less land requirement by operating a group of microcosm wetlands at a hydraulic retention time (HRT) of less than 4 d in southern Taiwan. An artificial wastewater, simulating municipal wastewater containing 200 mg L(-1) of chemical oxygen demand (COD), 20 mg L(-1) of NH4+-N (AN), and 20 mg L(-1) of PO4(3-)-P (OP), was the inflow source. Three emergent plants [reed, Phragmites australis (Cav.) Trin. ex Steud. ; water primrose, Ludwigia octovalvis (Jacq.) P.H. Raven; and dayflower, Commelina communis L. ] and two floating plants [water spinach, Ipomoea aquatica Forssk. ; and water lettuce, Pistia stratiotes L. ] plants were tested. The planted systems showed more nutrient removal than unplanted systems; however, the type of macrophytes in CW did not make a major difference in treatment. At the HRTs of 2 to 4 d, the planted system maintained greater than 72,80, and 46% removal for COD, AN, and OP, respectively. For AN and OP removal, the highest efficiencies occurred at the HRT of 3 d, whereas maximum removal rates for AN and OP occurred at the HRT of 2 d. Both removal rates and efficiencies were reduced drastically at the HRT of 1 d. Removals of COD, OP, and AN followed first-order reactions within the HRTs of 1 to 4 d. The efficient removals of these constituents obtained with HRT between 2 and 4 d indicated the possibility of using a CW system for wastewater treatment with less land requirement.
Lung cancer in chronic interstitial pneumonia: early manifestation from serial CT observations.

OBJECTIVE The purpose of this study was to use serial CT observations to characterize early-stage lung cancer in patients with chronic interstitial pneumonia. MATERIALS AND METHODS We found 23 lung cancers in 22 patients during routine follow-up of chronic interstitial pneumonia between 1999 and 2010. Patients with lung cancer found at initial CT were excluded. Two radiologists independently reviewed serial CT scans, determined the earliest scan showing lung cancer, and evaluated the tumor shape, size, density, and location. Delay in diagnosis was measured from the time of the earliest scan showing lung cancer and the subsequent clinical diagnosis. RESULTS During the mean follow-up period of 4.1 years, CT scans were obtained eight times on average. The median tumor size at presentation was 11 mm, and at clinical diagnosis was 22 mm. The median delay in diagnosis was 409 days. Fifteen tumors (65.2%) were in the interface between normal and fibrotic lung cysts (honeycomb cysts, paraseptal emphysema, and traction bronchiolectasis), four were in the area of ground-glass opacity, and one was in the midst of honeycomb cysts. Twelve tumors were round or oval, eight tumors had an ill-defined stellate shape, and two had a bandlike shape. One tumor appeared as an area of ill-defined increased lung attenuation. CONCLUSION Nearly one half of the tumors had a stellate or bandlike shape and were difficult to recognize as tumors initially. Most of the tumors were located at the interface between normal lung and fibrotic cysts; only rarely were tumors located in the midst of honeycomb cysts.
H2O2 sensitivity of afferent splanchnic C fiber units in vitro.

1. Single-unit impulse activity evoked by transient, focal application of hydrogen peroxide (H2O2) to identified visceral receptive fields has been characterized in an in vitro rat splanchnic nerve-mesentery preparation. In addition to H2O2 responsiveness, units were characterized in terms of sensitivity to mechanical stimuli, warming, and bradykinin. 2. Mesenteric receptive fields of single splanchnic afferent C fibers in vitro were located with the use of warm (approximately 45 degrees C saline) or mechanical search stimuli. After delimitation of the warm-sensitive and/or mechanosensitive receptive field, units were tested for responsiveness to transient, focal application of H2O2. Microliter volumes (usually 1 microliter) of H2O2 (88-880 mM) evoked responses in 25 of 42 (60%) units with identified warm-sensitive and/or mechanosensitive receptive fields, and in an additional 10 units for which H2O2 was the only effective stimulus. 3. Tachyphylaxis to repeated H2O2 stimulation was observed with interstimulus intervals <30 min, but did not indicate irreversible inactivation of the terminal, because 1) during this period warm and mechanical stimuli elicited responses equal to or greater than those before H2O2 treatment, and 2) H2O2 sensitivity was restored after units were allowed to recover. 4. Eight units unresponsive to an initial dose of H2O2 responded vigorously to a repeated application at the same site, suggesting a potentiating effect of prior H2O2 exposure. 5. Sixty-two percent (8 of 13) of H2O2-responsive units, but no (0 of 6) H2O2-unresponsive units responded to transient, focal bradykinin (9-90 nM) application. 6. An indirect mode of H2O2-evoked afferent excitation in some units was suggested by several observations, including the prolonged (up to 8 min) duration of the response of some units to transient H2O2 application, and the occasionally long (>2 min) response latencies to focal application of H2O2 to defined receptive fields. 7. Excitation of splanchnic neurons by H2O2 may be relevant to the modulation of reactive oxygen species production by immunocompetent cells, because sensory neuropeptides contained in these afferent fibers are known to influence the respiratory burst of macrophages and neutrophils.
Experimental research in evolutionary computation

We present a comprehensive, effective and very efficient methodology for the design and experimental analysis of search heuristics such as evolutionary algorithms, differential evolution, pattern search or even classical methods such as the Nelder-Mead simplex algorithm. Our approach extends the sequential parameter optimization (SPO) method that has been successfully applied as a tuning procedure to numerous heuristics for practical and theoretical optimization problems. The benefit of combining modern and classical statistical methods is demonstrated. Optimization practitioners receive valuable hints for choosing an adequate heuristic for their optimization problems - theoreticians receive guidelines for testing results systematically on real problem instances. We demonstrate how SPO improves the performance of many search heuristics significantly. However, this performance gain is not available for free. Therefore, costs of this tuning process are discussed. Several examples from theory and practice are used to illustrate typical pitfalls in experimentation. Software tools implementing procedures described in this tutorial are freely available.
Digit Recognizer : Classifying Digits Using a Convolutional Neural Network

The need to process handwritten documents still exists today despite growing adoption of electronic communication. For example, the postal service accepts packages and envelopes with handwritten addresses, and it is both impractical and expensive to have humans sort all of the mail. Additionally, many companies continue to provide means by which people can submit handwritten forms and other documentation. As the population and industrial sector continue to grow, so does the amount of handwritten data that needs to be processed. The expenses associated with paying human employees to sort through the data and enter the information manually into a computer becomes increasingly more time-consuming and expensive. Knowing this, it is easy to see that it would be beneficial to automate part or all of the process. Many techniques for automatically recognizing handwritten data have already been developed and tested over the past several years.
The Interferon (IFN)-stimulated Gene Sp100 Promoter Contains an IFN-γ Activation Site and an Imperfect IFN-stimulated Response Element Which Mediate Type I IFN Inducibility*

Expression of the nuclear domain-associated proteins Sp100, PML, and NDP52, is enhanced by interferons (IFNs) on the mRNA and protein level. Increase both of Sp100 and PML mRNA is due to enhanced transcription of the corresponding genes which occurs independently of cellular protein synthesis immediately upon IFN-β addition. Here, we describe the molecular cloning and functional analysis of the Sp100 promoter. DNA sequence analysis revealed potential binding sites for several constitutive and IFN-inducible transcription factors. Consistent with the absence of a TATA box and an initiator element, several transcription initiation sites were found. Transient expression studies identified an imperfect IFN-stimulated response element within the first 100 nucleotides upstream of the major transcription start site. This element rendered a heterologous promoter IFN-β-inducible and bound IFN-stimulated gene factor 2 strongly but IFN-stimulated gene factor 3 only weakly. An IFN-γ activation site approximately 500 base pairs upstream of the IFN-stimulated response element was found to bind three IFN-α/β activation factors upon IFN-β induction and conferred both type I and type II IFN inducibility upon a heterologous promoter. These data demonstrate a novel arrangement of a nonoverlapping IFN-γ activation site and an IFN-stimulated response element mediating type I IFN inducibility, previously not reported for other IFN-stimulable promoters.
Structure of the human lipid-gated cation channel TRPC 3 2 3

19 The TRPC channels are crucially involved in store-operated calcium entry and calcium 20 homeostasis, and they are implicated in human diseases such as neurodegenerative disease, 21 cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human 22 TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 23 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP 24 helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different 25 gating mechanism from other TRP subfamily channels. The third transmembrane helix S3 is 26 remarkably long, shaping a unique transmembrane domain, and constituting an extracellular 27 domain that may serve as a sensor of external stimuli. We identified two lipid binding sites, one 28 being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to 29 the ion-conducting pore, where the conserved LWF motif of the TRPC family is located. 30
Retirement and Unexpected Health Shocks January 2019

Is retirement good for your health? We complement previous studies by exploring the effect of retirement on unexpected health evolution. Using panel data from the Household, Income and Labour Dynamics in Australia survey (2001-2014), we construct measures of the mismatch between individual expected and actual health evolution (hereafter “health shocks”). In our approach, reverse causation running from health shocks to retirement is highly unlikely, because we look at shocks that happen at least a few months after retirement, and those shocks are, by definition, unanticipated. We find that retirement decreases the probability of negative shocks (by approximately 16% to 24% for males and 14% to 23% for females) while increasing the likelihood of positive shocks (by 9% to 14% for males and 10% to 13% for females). This result is robust to the use of different lead-lag structures and of alternative measures of health change. Our findings are thus consistent with a positive impact of retirement on health. We conclude that increasing the official retirement age may postpone the beneficial effect of retirement on health.
Effect of cellular changes and onset of humoral immunity on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs.

Twenty-two 4- to 5-week-old gnotobiotic pigs were intranasally inoculated with 10(6.0) TCID(50) of porcine reproductive and respiratory syndrome virus (PRRSV) (Lelystad) and euthanized at different time intervals post-inoculation (p.i.). Bronchoalveolar lavage (BAL) cell populations were characterized, together with the pattern of virus replication and appearance of antibodies in the lungs. Total BAL cell numbers increased from 140x10(6) at 5 days p.i. to 948x10(6) at 25 days p.i. and remained at high levels until the end of the experiment. The number of monocytes/macrophages, as identified by monoclonal antibodies 74-22-15 and 41D3, increased two- to fivefold between 9 and 52 days p.i. with a maximum at 25 days p.i. Flow cytometry showed that the population of differentiated macrophages was reduced between 9 and 20 days p.i. and that between the same time interval, both 74-22-15-positive and 41D3-negative cells, presumably monocytes, and 74-22-15- and 41D3-double negative cells, presumably non-phagocytes, entered the alveolar spaces. Virus replication was highest at 7 to 9 days p.i. , decreased slowly thereafter and was detected until 40 days p.i. Anti-PRRSV antibodies were detected starting at 9 days p.i. but neutralizing antibodies were only demonstrated in one pig euthanized at 35 days and another at 52 days p.i. The decrease of virus replication in the lungs from 9 days p.i. can be attributed to (i) shortage of susceptible differentiated macrophages, (ii) lack of susceptibility of the newly infiltrated monocytes and (iii) appearance of anti-PRRSV antibodies in the lungs. Neutralizing antibodies may contribute to the clearance of PRRSV from the lungs.
Choline-linked phosphoglycerides. A source of phosphatidic acid and diglycerides in stimulated neutrophils.

Stimulation of human polymorphonuclear leukocytes (PMN) may result in the metabolism of phospholipids other than phosphoinositides to generate second-messenger intermediary metabolites. We investigated agonist-induced breakdown of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (1-O-alkyl-2-acyl-GPC), which constitutes almost half the diradyl-GPC fraction in human PMN (Mueller, H. W., O'Flaherty, J. T., Green, D. G., Samuel, M. P., and Wykle, R. L. (1984) J. Lipid Res. 25: 383-388), in cells prelabeled with 1-O-[3H] alkyl-2-acyl-GPC. We also utilized normal-phase high pressure liquid chromatography to quantitate the accumulation of diradylglycerols (1-O-alkyl-2-acylglycerols and diacylglycerols) in stimulated PMN. Phorbol-12-myristate-13-acetate (PMA), 1-oleoyl-2-acetyl-sn-glycerol-, calcium ionophore A23187-, and f-methionyl-leucyl-phenylalanine (fMLP) stimulation of PMN resulted in a time- and concentration-dependent hydrolysis of 1-O-[3H]alkyl-2-acyl-GPC and the formation of 1-O-[3H]alkyl-2-acyl-phosphatidic acid (PA) and 1-O-[3H]alkyl-2-acylglycerol. In all cases formation of 1-O-[3H]alkyl-2-acyl-PA preceded that of 1-O-[3H]alkyl-2-acylglycerol. The times between addition of stimulus and appearance of 1-O-[3H] alkyl-2-acylglycerol varied for PMA (40 s at 1.6 microM), A23187 (5 min at 5 microM), and fMLP (30 sec at 1 microM). Preincubation of cells with 1 microgram/ml pertussis toxin (PT) inhibited the breakdown of 1-O-[3H]alkyl-2-acyl-GPC in cells stimulated with 1 microM fMLP, indicating a role for a PT-sensitive G protein with this stimulus. Quantitation of diglycerides as diradylglycerobenzoates in PMN stimulated with PMA (10 min), A23187 (10 min), or fMLP demonstrated marked accumulation of both 1-O-alkyl-2-acylglycerols and diacylglycerols. The highest increases over controls were observed for fMLP (33-fold for 1-O-alkyl-2-acylglycerols and 17-fold for diacylglycerols). In stimulated PMN prelabeled with 1-O-[3H]hexadecyl-2-acyl-GPC and 1-O-alkyl-2-acyl-sn-glycero-3-[32P]phosphocholine, the ratio of 3H to 32P in 1-O-alkyl-2-acyl-PA compared to 1-O-alkyl-2-acyl-GPC suggested the involvement of a phospholipase D in the hydrolysis of 1-O-[3H]-alkyl-2-acyl-GPC. Thus, stimulation of human PMN results in the hydrolysis of 1-O-[3H]alkyl-2-acyl-GPC to yield 1-O-[3H] alkyl-2-acyl-PA and 1-O-[3H]alkyl-2-acylglycerol possibly initiated by activation of a phospholipase D. (ABSTRACT TRUNCATED AT 250 WORDS)