Miracle-dz/UniFAR-FTUs huggingface dataset:
The orisome: structure and function

During the cell division cycle of all bacteria, DNA-protein complexes termed orisomes trigger the onset of chromosome duplication. Orisome assembly is both staged and stringently regulated to ensure that DNA synthesis begins at a precise time and only once at each origin per cycle. Orisomes comprise multiple copies of the initiator protein DnaA, which oligomerizes after interacting with specifically positioned recognition sites in the unique chromosomal replication origin, oriC. Since DnaA is highly conserved, it is logical to expect that all bacterial orisomes will share fundamental attributes. Indeed, although mechanistic details remain to be determined, all bacterial orisomes are capable of unwinding oriC DNA and assisting with loading of DNA helicase onto the single-strands. However, comparative analysis of oriCs reveals that the arrangement and number of DnaA recognition sites is surprisingly variable among bacterial types, suggesting there are many paths to produce functional orisome complexes. Fundamental questions exist about why these different paths exist and which features of orisomes must be shared among diverse bacterial types. In this review we present the current understanding of orisome assembly and function in Escherichia coli and compare the replication origins among the related members of the Gammaproteobacteria. From this information we propose that the diversity in orisome assembly reflects both the requirement to regulate the conformation of origin DNA as well as to provide an appropriate cell cycle timing mechanism that reflects the lifestyle of the bacteria. We suggest that identification of shared steps in orisome assembly may reveal particularly good targets for new antibiotics.
Genes Involved in Degradation of para-Nitrophenol Are Differentially Arranged in Form of Non-Contiguous Gene Clusters in Burkholderia sp. strain SJ98

Biodegradation of para-Nitrophenol (PNP) proceeds via two distinct pathways, having 1,2,3-benzenetriol (BT) and hydroquinone (HQ) as their respective terminal aromatic intermediates. Genes involved in these pathways have already been studied in different PNP degrading bacteria. Burkholderia sp. strain SJ98 degrades PNP via both the pathways. Earlier, we have sequenced and analyzed a ~41 kb fragment from the genomic library of strain SJ98. This DNA fragment was found to harbor all the lower pathway genes; however, genes responsible for the initial transformation of PNP could not be identified within this fragment. Now, we have sequenced and annotated the whole genome of strain SJ98 and found two ORFs (viz., pnpA and pnpB) showing maximum identity at amino acid level with p-nitrophenol 4-monooxygenase (PnpM) and p-benzoquinone reductase (BqR). Unlike the other PNP gene clusters reported earlier in different bacteria, these two ORFs in SJ98 genome are physically separated from the other genes of PNP degradation pathway. In order to ascertain the identity of ORFs pnpA and pnpB, we have performed in-vitro assays using recombinant proteins heterologously expressed and purified to homogeneity. Purified PnpA was found to be a functional PnpM and transformed PNP into benzoquinone (BQ), while PnpB was found to be a functional BqR which catalyzed the transformation of BQ into hydroquinone (HQ). Noticeably, PnpM from strain SJ98 could also transform a number of PNP analogues. Based on the above observations, we propose that the genes for PNP degradation in strain SJ98 are arranged differentially in form of non-contiguous gene clusters. This is the first report for such arrangement for gene clusters involved in PNP degradation. Therefore, we propose that PNP degradation in strain SJ98 could be an important model system for further studies on differential evolution of PNP degradation functions.
Simple three-pool model accurately describes patterns of long-term litter decomposition in diverse climates

As atmospheric CO2 increases, ecosystem carbon sequestration will largely depend on how global changes in climate will alter the balance between net primary production and decomposition. The response of primary production to climatic change has been examined using well-validated mechanistic models, but the same is not true for decomposition, a primary source of atmospheric CO2. We used the Long-term Intersite Decomposition Experiment Team (LIDET) dataset and model-selection techniques to choose and parameterize a model that describes global patterns of litter decomposition. Mass loss was best represented by a three-pool negative exponential model, with a rapidly decomposing labile pool, an intermediate pool representing cellulose, and a recalcitrant pool. The initial litter lignin/nitrogen ratio defined the size of labile and intermediate pools. Lignin content determined the size of the recalcitrant pool. The decomposition rate of all pools was modified by climate, but the intermediate pool’s decomposition rate was also controlled by relative amounts of litter cellulose and lignin (indicative of ligninencrusted cellulose). The effect of climate on decomposition was best represented by a composite variable that multiplied a water-stress function by the Lloyd and Taylor variable Q10 temperature function. Although our model explained nearly 70% of the variation in LIDET data, we observed systematic deviations from model predictions. Belowand aboveground material decomposed at notably different rates, depending on the decomposition stage. Decomposition in certain ecosystem-specific environmental conditions was not well represented by our model; this included roots in very wet and cold soils, and aboveground litter in N-rich and arid sites. Despite these limitations, our model may still be extremely useful for global modeling efforts, because it accurately (R 5 0.6804) described general patterns of long-term global decomposition for a wide array of litter types, using relatively minimal climatic and litter quality data.
Evolution and CNO yields of Z = 10-5 stars and possible effects on carbon-enhanced metal-poor production

Aims. Our main goals are to get a deeper insight into the evolution and final fates of intermediate-mass, extremely metal-poor (EMP) stars. We also aim to investigate the C, N, and O yields of these stars. Methods. Using the Monash University Stellar Evolution code MONSTAR we computed and analysed the evolution of stars of metallicity Z = 10-5 and masses between 4 and 9 M? , from their main sequence until the late thermally pulsing (super) asymptotic giant branch, TP-(S)AGB phase. Results. Our model stars experience a strong C, N, and O envelope enrichment either due to the second dredge-up process, the dredge-out phenomenon, or the third dredge-up early during the TP-(S)AGB phase. Their late evolution is therefore similar to that of higher metallicity objects. When using a standard prescription for the mass loss rates during the TP-(S)AGB phase, the computed stars are able to lose most of their envelopes before their cores reach the Chandrasekhar mass (mCh), so our standard models do not predict the occurrence of SNI1/2 for Z = 10-5 stars. However, we find that the reduction of only one order of magnitude in the mass-loss rates, which are particularly uncertain at this metallicity, would prevent the complete ejection of the envelope, allowing the stars to either explode as an SNI1/2 or become an electron-capture SN. Our calculations stop due to an instability near the base of the convective envelope that hampers further convergence and leaves remnant envelope masses between 0.25 M? for our 4 M? model and 1.5 M? for our 9 M? model. We present two sets of C, N, and O yields derived from our full calculations and computed under two different assumptions, namely, that the instability causes a practically instant loss of the remnant envelope or that the stars recover and proceed with further thermal pulses. Conclusions. Our results have implications for the early chemical evolution of the Universe and might provide another piece for the puzzle of the carbon-enhanced EMP star problem.
Learning the Scope of Negation in Biomedical Texts

In this paper we present a machine learning system that finds the scope of negation in biomedical texts. The system consists of two memory-based engines, one that decides if the tokens in a sentence are negation signals, and another that finds the full scope of these negation signals. Our approach to negation detection differs in two main aspects from existing research on negation. First, we focus on finding the scope of negation signals, instead of determining whether a term is negated or not. Second, we apply supervised machine learning techniques, whereas most existing systems apply rule-based algorithms. As far as we know, this way of approaching the negation scope finding task is novel.
Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia

Sequential combination of cytogenetics and RNA-sequencing (RNA-Seq) has been shown to be an efficient approach to detect pathogenetically important fusion genes in neoplasms carrying only one or a few chromosomal rearrangements. We performed RNA-Seq on an acute myeloid leukemia in a 2-year-old girl with the karyotype 46,XX,add(1)(p36), der(2)t(2;3)(q21;q21),del(3)(q21),der(10)t(1;10)(q32;q24),der(16)(2qter-->2q21::16p11-->16q24::16p11-->16pter)[13]/46,XX[2] and identified a cryptic FUS/ERG fusion gene. PCR and direct sequencing verified the presence of the FUS-ERG chimeric transcript in which exon 7 of FUS from 16p11 (nt 904 in sequence with accession number NM_004960 version 3) was fused in frame to exon 8 of ERG from sub-band 21q22.2 (nt 967 in NM_004449 version 4). The FUS-ERG transcript found here has been reported in only two other cases of childhood leukemia, in a 1-year-old boy and an 8-month-old boy, both diagnosed with precursor B cell ALL. The fusion transcript codes for a 497 amino acid residues FUS-ERG protein and, similar to other AML-related FUS-ERG fusion proteins, contains both functional domains (TR1 and TR2) of the transactivation domain of FUS and the ETS domain of ERG. The clinical significance, if any, of the amino acid residues which are coded by the exons 8, 9 and 10 of ERG in the fusion FUS-ERG proteins, remains unclear.
Optical Coherence Tomographic Observation of In-Stent Neoatherosclerosis in Lesions With More Than 50% Neointimal Area Stenosis After Second-Generation Drug-Eluting Stent Implantation

Background—Despite the enhanced properties of the second-generation drug-eluting stent (DES), its association with neoatherosclerosis has not been sufficiently evaluated. Therefore, we sought to evaluate and compare neoatherosclerosis in second-generation DESs to first-generation DESs. Methods and Results—A total of 212 DES-treated patients with >50% percent neointimal cross-sectional area stenosis were retrospectively enrolled from the Korean multicenter optical coherence tomography (OCT) registry. Within this population, 111 patients had a second-generation DES (40 zotarolimus, 36 everolimus, and 35 biolimus) and 101 patients had a first-generation (65 sirolimus and 36 paclitaxel) DES. Neoatherosclerosis on OCT was defined as neointima formation with the presence of lipids or calcification. OCT-determined neoatherosclerosis was identified in 27.4% (58/212) of all DES-treated lesions. The frequency of neoatherosclerosis increased with the stent age. Stent age was shorter in the second-generation DES group (12.4 months versus 55.4 months, P<0.001), and neoatherosclerosis was less frequently observed in that group (10.8% versus 45.5%, P<0.001). However, after adjusting for cardiovascular risk factors, chronic kidney disease (odds ratio, 4.113; 95% confidence interval, 1.086–15.575; P=0.037), >70 mg/dL of low-density cholesterol at follow-up OCT (odds ratio, 2.532; 95% confidence interval, 1.054–6.084; P=0.038), and stent age (odds ratio, 1.710; 95% confidence interval, 1.403–2.084; P<0.001) were all independent predictors for neoatherosclerosis, whereas the type of DES (first- versus second-generation) was not. Patients with neoatherosclerosis showed a higher rate of acute coronary syndrome at follow-up OCT (19.0% versus 3.9%, respectively, P=0.001). Conclusions—The second-generation DES is not more protective against neoatherosclerosis compared with the first-generation DES.
Molecular cloning and characterization of Mustang, a novel nuclear protein expressed during skeletal development and regeneration

Bone regeneration occurs as a series of events that requires temporal and spatial orchestration of numerous cell types guided by the transcriptional activity of thousands of genes, as recently demonstrated by our laboratory. Using the rat femoral fracture model, bioinformatics, cloning, expression assays, fusion proteins, and transfection, we report on the identification and characterization of one such differentially expressed gene, termed Mustang (musculoskeletal temporally activated novel gene). Mustang encodes for an 82 amino acid nuclear protein with no homology to any known protein family. However, other species homologues (mouse, human, cow) were identified within EST (expressed sequence tag) databases. Nuclear localization was confirmed using a GFP‐Mustang fusion protein. Using in situ hybridization, Mustang expression was localized to differentiating periosteal osteogenic cells, proliferating chondrocytes, and osteoblasts of the fracture callus. Unlike adult tissues, developing embryos abundantly express Mustang, especially in mesenchymal condensations of limbs, vertebral perichondrium, and mesenchymal cells of the intervertebral discs. Although the precise function of Mustang is unknown, its unique pattern of expression during bone development and regeneration, absence in adult tissues (except skeletal muscle and tendon), and nuclear localization suggest that Mustang is involved in the development and regeneration of the mammalian musculoskeletal system. —Lombardo, F. , Komatsu, D. , Hadjiargyrou, M. Molecular cloning and characterization of Mustang, a novel nuclear protein expressed during skeletal development and regeneration. —Lombardo, F. , Komatsu, D. , Hadjiargyrou, M. Molecular cloning and characterization of Mustang, a novel nuclear protein expressed during skeletal development and regeneration. FASEB J. 18, 52–61 (2004)
Effect of Seasonal Variation on Adult Clinical Laboratory Parameters in Rwanda, Zambia, and Uganda: Implications for HIV Biomedical Prevention Trials

Objectives To investigate the effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda and determine its implications for HIV prevention and other clinical trials. Methods Volunteers in a cross-sectional study to establish laboratory reference intervals were asked to return for a seasonal visit after the local season had changed from dry to rainy or vice versa. Volunteers had to be clinically healthy, not pregnant and negative for HIV, Hepatitis B and C, and syphilis infection at both visits. At each visit, blood was taken for measurement of hemoglobin, haematocrit, mean corpuscular volume, red blood cells, platelets, total white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, CD4/CD8 T cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin, total immunoglobulin gamma, total protein, creatinine, total amylase, creatine phosphokinase and lactate dehydrogenase (LDH). Consensus dry season reference intervals were applied to rainy season values (and vice versa) and the proportion of ‘out-of-range’ values determined. Percentage differences between dry and rainy season parameter mean values were estimated. Results In this cohort of 903 volunteers, less than 10.0% of consensus parameter (except LDH) values in one season were “out-of-range” in the other. Twenty-two (22) percent of rainy season LDH values fell outside of the consensus dry season interval with the higher values observed in the rainy season. Variability between consensus seasonal means ranged from 0.0% (total WBC, neutrophils, monocytes, basophils, and direct bilirubin) to 40.0% (eosinophils). Within sites, the largest seasonal variations were observed for monocytes (Masaka, 11.5%), LDH (Lusaka, 21.7%), and basophils (Kigali, 22.2%). Conclusions Seasonality had minimal impact on adult clinical laboratory parameter values in Rwanda, Zambia, and Uganda. Seasonal variation may not be an important factor in the evaluation of adult clinical laboratory parameters in HIV prevention and other clinical trials in these countries.
State‐dependent changes in astrocyte regulation of extrasynaptic NMDA receptor signalling in neurosecretory neurons

Non‐technical summary Glutamate is a critical excitatory neurotransmitter in the modulation of hypothalamic neuronal activity and neurosecretion from the posterior pituitary. Still, the precise mechanisms and modalities by which it acts remain to be fully elucidated. We show that in addition to mediating conventional fast synaptic transmission, glutamate persistently activates extrasynaptic NMDA receptors, providing a tonic excitatory drive to hypothalamic neurosecretory neurons. We also show that this tonic excitatory modality is influenced by the neighbouring astrocytes, and is enhanced in dehydrated rats. Knowledge on alternative modalities by which glutamate influences hypothalamic neuronal function increases our understanding of general brain mechanisms regulating neurosecretion and bodily homeostasis.
Target Visibility in the Standing Wave Illusion: Is Mask—Target Shape Similarity Important?

The perceptibility of a flickering central bar can be dramatically reduced by the presence of two flanking bars presented in counterphase. This phenomenon, known as the ‘standing wave illusion’, has been suggested to involve local edge interactions (Macknik et al, 2000 Proceedings of the National Academy of Sciences of the USA 97 7556–7560). High-level re-entrant mechanisms have also been implicated. Enns (2002, Psychonomic Bulletin & Review 9 489–496) reports an association between the reported viability of the centre bar and its similarity in shape with the flanking bars. We find that this relationship between shape similarity and reported visibility seems to be contingent on the degree of experienced apparent motion. When target duration is shortened, so reducing apparent motion, reports of visibility reflect the amount of abutting contour. In a further experiment we find that luminance discriminations of the centre bar are related to the amount of abutting contour not to shape similarity. This is despite experiment 3 being conducted at stimulus durations for which experiment 2 visibility ratings indicated that shape similarity is important and contour is not. We suggest that this perceived motion may be the factor mediating shape ‘effects’ in the reported visibility task. We propose that the absence of such shape effects in the discrimination task may be because the task provides an objective measure of visibility that is immune to bias from perceived motion. We also speculate that while target luminance information may be immune to masking resulting from perceived motion, it may be subject to masking due to lateral inhibition.
Parental social anxiety disorder prospectively predicts toddlers' fear/avoidance in a social referencing paradigm.

BACKGROUND Anxiety runs in families. Observational learning of anxious behavior from parents with anxiety disorders plays an important role in the intergenerational transmission of anxiety. We investigated the link between parental anxiety (parental lifetime anxiety disorders and expressed parental anxiety) and toddler fear/avoidance during social referencing (SR) situations. METHOD Toddlers (N = 117) participated with both parents (with lifetime social anxiety disorder, other nonsocial anxiety disorders, lifetime comorbid social and other anxiety disorders, or without anxiety disorders) in a longitudinal study. Behavioral inhibition (BI) was measured at 12 months via observational tasks. At 30 months, children were confronted with a stranger and a remote-control robot in SR situations, separately with each parent. Children's fear and avoidance, and parents' expressions of anxiety, encouragement, and overcontrol were observed. RESULTS Toddlers of parents with lifetime social anxiety disorder (alone and comorbid with other anxiety disorders) showed more fear/avoidance in SR situations than toddlers of parents without anxiety disorders, while the effect of other anxiety disorders alone was not significant. Although expressed parental anxiety at 30 months in SR situations did not significantly predict toddlers' fear/avoidance, higher levels of expressed anxiety at 12 months in SR situations by parents with comorbid social and other anxiety disorders predicted higher levels of fear/avoidance. BI at 12 months predicted toddlers' fear/avoidance only with mothers, but not with fathers. CONCLUSIONS Parental lifetime social anxiety disorders may be a stronger predictor of children's fear/avoidance than parents' expressions of anxiety in SR situations in toddlerhood. End of infancy may be a sensitive time for learning of anxiety from parents with comorbid lifetime social and nonsocial anxiety disorders in SR situations. Fathers are as important as mothers in the transmission of anxiety via SR. Furthermore, children may act relatively free of their early temperament in SR situations with fathers.
Applied Economics Workshop Business 33610 Autumn Quarter 2012 "forced Coexistence and Economic Development: Evidence from Native American Reservations" Forced Coexistence and Economic Development: Evidence from Native American Reservations

There are large differences in economic development across Native American reservations today. This paper asks whether these differences can be in part explained by the forced integration of historically autonomous sub-tribal bands in the 19th century. To measure forced integration, I combine anthropological data on intra-tribal political integration in pre-reservation times with historical information on the constituent bands of each reservation. Exploring variation in how politically integrated tribes were before reservations and variation in how politically integrated reservations were at the time of their formation, I find that forced integration lowers per capita incomes today by about 30 percent. To account for potential selection into forced integration, I exploit historical mining rushes as a source of exogenous variation in the government's incentive to combine bands onto reservations. The IV strategy confirms the baseline results. I also provide quantitative evidence on the channels through which forced integration affects incomes today. for insightful comments and valuable discussions. I also thank Matthew Baker for sharing the Ethnographic Atlas data and Richard Jantz for sharing the Franz Boas anthropometric data.
Dextran restores albumin-inhibited surface activity of pulmonary surfactant extract.

We examined the effect of dextran (molecular weight 71,000) in counteracting the surfactant inhibitory action of plasma albumin. The surface adsorption time of 0.5 mg/ml modified natural surfactant (MNS; porcine lung extract consisting of phospholipids and hydrophobic surfactant proteins) with 7.5 mg/ml albumin decreased from 681 to 143 s by addition of dextran at a concentration of 10 mg/ml (P < 0.01). The minimum surface tension of 2.0 mg/ml MNS with 30 mg/ml albumin decreased from over 21 mN/m to below 3 mN/m when dextran was added at a concentration of 10 mg/ml (P < 0.01). Surfactant-deficient newborn rabbits given 10 ml/kg of a liquid containing 2.0 mg/ml MNS with 30 mg/ml albumin had a mean tidal volume </=5 ml/kg after 5 min of mechanical ventilation, but, in those animals given the liquid containing 10 mg/ml dextran also, the volume was >13 ml/kg (P < 0.05). Although the underlying mechanism remains to be elucidated, we conclude that dextran restores the albumin-inhibited surface activity of MNS.