Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-phylog: an assembly-free phylogenomic approach for closely related organisms

With the advent of high-throughput sequencing technologies, the rapid generation and accumulation of large amounts of sequencing data pose an insurmountable demand for efficient algorithms for constructing whole-genome phylogenies. The existing phylogenomic methods all use assembled sequences, which are often not available owing to the difficulty of assembling short-reads; this obstructs phylogenetic investigations on species without a reference genome. In this report, we present co-phylog, an assembly-free phylogenomic approach that creates a ‘micro-alignment’ at each ‘object’ in the sequence using the ‘context’ of the object and calculates pairwise distances before reconstructing the phylogenetic tree based on those distances. We explored the parameters’ usages and the optimal working range of co-phylog, assessed co-phylog using the simulated next-generation sequencing (NGS) data and the real NGS raw data. We also compared co-phylog method with traditional alignment and alignment-free methods and illustrated the advantages and limitations of co-phylog method. In conclusion, we demonstrated that co-phylog is efficient algorithm and that it delivers high resolution and accurate phylogenies using whole-genome unassembled sequencing data, especially in the case of closely related organisms, thereby significantly alleviating the computational burden in the genomic era.
Innovation in the collective brain

Innovation is often assumed to be the work of a talented few, whose products are passed on to the masses. Here, we argue that innovations are instead an emergent property of our species' cultural learning abilities, applied within our societies and social networks. Our societies and social networks act as collective brains. We outline how many human brains, which evolved primarily for the acquisition of culture, together beget a collective brain. Within these collective brains, the three main sources of innovation are serendipity, recombination and incremental improvement. We argue that rates of innovation are heavily influenced by (i) sociality, (ii) transmission fidelity, and (iii) cultural variance. We discuss some of the forces that affect these factors. These factors can also shape each other. For example, we provide preliminary evidence that transmission efficiency is affected by sociality—languages with more speakers are more efficient. We argue that collective brains can make each of their constituent cultural brains more innovative. This perspective sheds light on traits, such as IQ, that have been implicated in innovation. A collective brain perspective can help us understand otherwise puzzling findings in the IQ literature, including group differences, heritability differences and the dramatic increase in IQ test scores over time.
Detection of a protein, similar to the sex pilus subunit, in the outer membrane of Escherichia coli cells carrying a derepressed F-like R factor

The outer membranes of Escherichia coli K-12 cells carrying a derepressed F-like R factor contain about 7 times 10-4 molecules per cell of a protein similar to the subunit of the sex pili specified by the R factor. This protein pool is absent in cells carrying the repressed variant of the R factor. The size of the pool is about one-half of the amount of protein incorporated into mature sex pili at the peak of production and is independent of the phase of growth of the culture. The molecular weight of the protein in the pool and of the subunit of the sex pili specified by the cells is 12,500 plus or minus 600.
The organization and connections of somatosensory cortex in marmosets

Microelectrode mapping methods were used to define and describe 3 representations of the body surface in somatosensory cortex of marmosets: S-I proper or area 3b of anterior parietal cortex, S-II, and the parietal ventral area (PV) of the upper bank of the lateral sulcus. In the same animals, injections of anatomical tracers were placed into electrophysiologically determined sites in area 3b or S-II. Mapping results and patterns of connections were later related to architectonic fields that were delimited in sections cut parallel to the surface of manually flattened cortex and stained for myelin. There were several major results. (1) Recordings from area 3b revealed a characteristic somatotopic organization of foot to face in a mediolateral sequence as previously reported in other members of the marmoset family (Carlson et al., 1986). (2) Multiple injections of WGA-HRP in area 3b demonstrated dense, patchy interconnections with ipsilateral S-II, PV, area 3a, and area 1, less dense interconnections with primary motor cortex (M-I), the supplementary motor area (SMA), limbic cortex of the medial wall (L), and rostrolateral parietal cortex of the lateral sulcus (PR), and callosal connections with areas 3b, S-II, and PV. Injections of 3 different tracers into the representation of 3 body regions in area 3b indicated that the connections with areas 3a, 3b, 1, S-II, and PV are topographically organized. (3) Recordings from cortex on the upper bank of the lateral sulcus demonstrated a somatotopic representation of the body surface that matches that of S-II of other mammals. S-II immediately adjoined areas 3b along the dorsal lip of the lateral sulcus. The face representation in S-II was adjacent to the face representation in 3b while the trunk, hindlimb, and forelimb were represented in a caudorostral sequence deeper in the sulcus. (4) Injections in S-II revealed ipsilateral connections with areas 3a, 3b, 1, a presumptive area 2, PV, PR, M-I, SMA, limbic cortex, the frontal eye fields, and the frontal ventral visual area. Dense callosal connections were with S-II and PV. (5) The recordings also revealed a systematic representation just rostral to S-II that has not been previously described in primates. (ABSTRACT TRUNCATED AT 400 WORDS)
Self-Regulation Through Goal Setting

Goals are an important source of motivation. But little is known about why and how people set them. We address these questions in a model based on two stylized facts from psychology and behavioral economics: i) Goals serve as reference points for performance. ii) Present-biased preferences create self-control problems. We show how goals permit self-regulation, but also that they are painful self-disciplining devices. Greater self-control problems therefore lead to stronger self-regulation through goals only up to a certain point. For severely present-biased preferences, the required goal for self-regulation is too painful and the individual rather gives up.
Histone Demethylase Jumonji D3 (JMJD3) as a Tumor Suppressor by Regulating p53 Protein Nuclear Stabilization

Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.
Controlled interplay between trigger loop and Gre factor in the RNA polymerase active centre

The highly processive transcription by multi-subunit RNA polymerases (RNAP) can be interrupted by misincorporation or backtracking events that may stall transcription or lead to erroneous transcripts. Backtracked/misincorporated complexes can be resolved via hydrolysis of the transcript. Here, we show that, in response to misincorporation and/or backtracking, the catalytic domain of RNAP active centre, the trigger loop (TL), is substituted by transcription factor Gre. This substitution turns off the intrinsic TL-dependent hydrolytic activity of RNAP active centre, and exchanges it to a far more efficient Gre-dependent mechanism of RNA hydrolysis. Replacement of the TL by Gre factor occurs only in backtracked/misincorporated complexes, and not in correctly elongating complexes. This controlled switching of RNAP activities allows the processivity of elongation to be unaffected by the hydrolytic activity of Gre, while ensuring efficient proofreading of transcription and resolution of backtracked complexes.
Neuromuscular Activation of the Vastus Intermedius Muscle during Isometric Hip Flexion

Although activity of the rectus femoris (RF) differs from that of the other synergists in quadriceps femoris muscle group during physical activities in humans, it has been suggested that the activation pattern of the vastus intermedius (VI) is similar to that of the RF. The purpose of present study was to examine activation of the VI during isometric hip flexion. Ten healthy men performed isometric hip flexion contractions at 25%, 50%, 75%, and 100% of maximal voluntary contraction at hip joint angles of 90°, 110° and 130°. Surface electromyography (EMG) was used to record activity of the four quadriceps femoris muscles and EMG signals were root mean square processed and normalized to EMG amplitude during an isometric knee extension with maximal voluntary contraction. The normalized EMG was significantly higher for the VI than for the vastus medialis during hip flexion at 100% of maximal voluntary contraction at hip joint angles of 110° and 130° (P < 0.05). The onset of VI activation was 230–240 ms later than the onset of RF activation during hip flexion at each hip joint angle, which was significantly later than during knee extension at 100% of maximal voluntary contraction (P < 0.05). These results suggest that the VI is activated later than the RF during hip flexion. Activity of the VI during hip flexion might contribute to stabilize the knee joint as an antagonist and might help to smooth knee joint motion, such as in the transition from hip flexion to knee extension during walking, running and pedaling.
Primacy of Warmth Versus Competence: A Motivated Bias?

ABSTRACT In line with previous results that challenge the traditional primacy of warmth over competence in outgroup perception, we propose to bridge elements from stereotype content model and social identity theory: Perceivers will use the competence and warmth dimensions differentially when interpreting higher or lower status outgroup members' behavior. We test the hypothesis that the dimension that is less favorable for the outgroup and more favorable for the ingroup will be used. In particular, we investigate whether the warmth dimension would better predict the interpretation of higher status outgroup members' behavior than the competence dimension, whereas the competence dimension would better predict the interpretation of lower status outgroup members' behavior than the warmth dimension. Two studies separately test these effects. Results suggest the existence of a motivated bias in interpreting outgroup members' behavior, especially when there is ingroup identification.
Effect of ceramic-impregnated "thermoflow" gloves on patients with Raynaud's syndrome: randomized, placebo-controlled study.

OBJECTIVE To determine the efficacy of ceramic impregnated gloves in the treatment of Raynaud's syndrome. DESIGN Double-blind, placebo-controlled study. SETTING Teaching hospital outpatient clinic. PARTICIPANTS Ninety-three patients meeting the "Pal" criteria for Raynaud's syndrome. INTERVENTIONS Treatment period of three months with use of ceramic-impregnated gloves. MAIN OUTCOME MEASURES Primary end points: Pain visual analogue scale ratings and diary; Disabilities of the Arm, Shoulder, Hand questionnaire; Jamar grip strength; Purdue board test of hand dexterity. Secondary end points: Infrared skin temperature measurements; seven-point Likert scale rating of treatment. RESULTS In 60 participants with complete data, improvements were noted in the visual analogue scale rating (p=0.001), DASH score (p=0.001), Jamar grip strength (p=0.002), infrared skin fingertip temperature (p=0.003), Purdue hand dexterity test (p=0.0001) and the Likert scale (p=0.001) with ceramic gloves over the placebo cotton gloves. CONCLUSION The ceramic-impregnated "thermoflow" gloves have a clinically important effect in Raynaud's syndrome.
Diagnostic Performance of a Multiple Real-Time PCR Assay in Patients with Suspected Sepsis Hospitalized in an Internal Medicine Ward

ABSTRACT Early identification of causative pathogen in sepsis patients is pivotal to improve clinical outcome. SeptiFast (SF), a commercially available system for molecular diagnosis of sepsis based on PCR, has been mostly used in patients hospitalized in hematology and intensive care units. We evaluated the diagnostic accuracy and clinical usefulness of SF, compared to blood culture (BC), in 391 patients with suspected sepsis, hospitalized in a department of internal medicine. A causative pathogen was identified in 85 patients (22%). Sixty pathogens were detected by SF and 57 by BC. No significant differences were found between the two methods in the rates of pathogen detection (P = 0.74), even after excluding 9 pathogens which were isolated by BC and were not included in the SF master list (P = 0.096). The combination of SF and BC significantly improved the diagnostic yield in comparison to BC alone (P < 0.001). Compared to BC, SF showed a significantly lower contamination rate (0 versus 19 cases; P < 0.001) with a higher specificity for pathogen identification (1.00, 95% confidence interval [CI] of 0.99 to 1.00, versus 0.94, 95% CI of 0.90 to 0.96; P = 0.005) and a higher positive predictive value (1.00, 95% CI of 1.00 to 0.92%, versus 0.75, 95% CI of 0.63 to 0.83; P = 0.005). In the subgroup of patients (n = 191) who had been receiving antibiotic treatment for ≥24 h, SF identified more pathogens (16 versus 6; P = 0.049) compared to BC. These results suggest that, in patients with suspected sepsis, hospitalized in an internal medicine ward, SF could be a highly valuable adjunct to conventional BC, particularly in patients under antibiotic treatment.
Minireview: thyrotropin receptor signaling in development and differentiation of the thyroid gland: insights from mouse models and human diseases.

N 1927, UHLENHUTH (1) demonstrated that the anterior lobe of the pituitary gland of salamanders produces a factor capable of controlling the function of the thyroid. This factor was subsequently called TSH. Forty years later, Pastan and co-workers (2) demonstrated that TSH exerts its effects through a protease-sensitive structure on the thyroid cell plasma membrane, thus postulating the existence of a specific receptor (TSH-R; the current official name is Tshr for mouse genetic locus and TSHR for the human locus). The relevance of the interaction between TSH and its receptor in the physiology and pathology of the thyroid became immediately clear, and indeed in 1968 Stanbury (3) suggested that congenital hypothyroidism in the absence of goiter could be due to an impaired response to TSH. The mechanisms triggered by Tshr upon interaction with the ligand, which regulate both proliferation and function of thyroid cells, have been exhaustively studied mainly in cell culture models. Several comprehensive reviews summarize these aspects of TSH signaling (4 – 8). This review will focus on a different aspect of TSH signaling, its role in the development and differentiation of the thyroid, as determined by the study of alterations in this pathway in both mice and humans. Indeed, these studies have provided important insights about the physiological roles of TSH/Tshr signaling, in some cases underscoring the pivotal role that this system plays in regulating the size and function of the thyroid gland; in others demoting it to, at best, a marginal modulator. Furthermore, the animal models have been useful in discovering new important functions of such signaling systems in extrathyroidal tissues (9), which are beyond the scope of this review. Animal models with impaired TSH/Tshr signaling Several mutant mouse lines that lack either a functional Tshr or TSH have been reported and described. Tshr hyt /Tshr hyt
Mono-Exponential Fitting in T2-Relaxometry: Relevance of Offset and First Echo

Introduction T2 relaxometry has become an important tool in quantitative MRI. Little focus has been put on the effect of the refocusing flip angle upon the offset parameter, which was introduced to account for a signal floor due to noise or to long T2 components. The aim of this study was to show that B1 imperfections contribute significantly to the offset. We further introduce a simple method to reduce the systematic error in T2 by discarding the first echo and using the offset fitting approach. Materials and Methods Signal curves of T2 relaxometry were simulated based on extended phase graph theory and evaluated for 4 different methods (inclusion and exclusion of the first echo, while fitting with and without the offset). We further performed T2 relaxometry in a phantom at 9.4T magnetic resonance imaging scanner and used the same methods for post-processing as in the extended phase graph simulated data. Single spin echo sequences were used to determine the correct T2 time. Results The simulation data showed that the systematic error in T2 and the offset depends on the refocusing pulse, the echo spacing and the echo train length. The systematic error could be reduced by discarding the first echo. Further reduction of the systematic T2 error was reached by using the offset as fitting parameter. The phantom experiments confirmed these findings. Conclusion The fitted offset parameter in T2 relaxometry is influenced by imperfect refocusing pulses. Using the offset as a fitting parameter and discarding the first echo is a fast and easy method to minimize the error in T2, particularly for low to intermediate echo train length.
Selective Inhibition of Selenocysteine tRNA Maturation and Selenoprotein Synthesis in Transgenic Mice Expressing Isopentenyladenosine-Deficient Selenocysteine tRNA

ABSTRACT Selenocysteine (Sec) tRNA (tRNA[Ser]Sec) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein biosynthesis of overexpressing either the wild type or a mutant tRNA[Ser]Sec lacking the modified base, isopentenyladenosine, in its anticodon loop were examined by introducing multiple copies of the corresponding tRNA[Ser]Sec genes into the mouse genome. Overexpression of wild-type tRNA[Ser]Sec did not affect selenoprotein synthesis. In contrast, the levels of numerous selenoproteins decreased in mice expressing isopentenyladenosine-deficient (i6A−) tRNA[Ser]Sec in a protein- and tissue-specific manner. Cytosolic glutathione peroxidase and mitochondrial thioredoxin reductase 3 were the most and least affected selenoproteins, while selenoprotein expression was most and least affected in the liver and testes, respectively. The defect in selenoprotein expression occurred at translation, since selenoprotein mRNA levels were largely unaffected. Analysis of the tRNA[Ser]Sec population showed that expression of i6A− tRNA[Ser]Sec altered the distribution of the two major isoforms, whereby the maturation of tRNA[Ser]Sec by methylation of the nucleoside in the wobble position was repressed. The data suggest that the levels of i6A− tRNA[Ser]Sec and wild-type tRNA[Ser]Sec are regulated independently and that the amount of wild-type tRNA[Ser]Sec is determined, at least in part, by a feedback mechanism governed by the level of the tRNA[Ser]Sec population. This study marks the first example of transgenic mice engineered to contain functional tRNA transgenes and suggests that i6A−tRNA[Ser]Sec transgenic mice will be useful in assessing the biological roles of selenoproteins.
Hospital Dissemination of tst-1-Positive Clonal Complex 5 (CC5) Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA), is one of the most prevalent clinical pathogens isolated from hospital settings, and has increasingly identified in community settings. In China, the SCCmecIII-ST239 strains are disseminated in different geographic regions, accounting for >75% of all MRSA isolates in some national studies. Here we characterized 150 non-duplicate MRSA isolates collected from February 2012 to May 2013 in a tertiary hospital in Suzhou, Eastern China, to explore the molecular epidemiology. All isolates were characterized by spa typing, SCCmec typing, and detection of genes encoding Panton-Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST-1). Representative genotypes were also subjected to multilocus sequence typing (MLST). Antibiotic susceptibility testing was performed using BD Phoenix™ Automated Microbiology System. Molecular typing identified 11 clonal complex (CC) and 28 spa types, with the CC5-spa t002 (29.3%) and CC239-spa t037 (14.7%) being the most prevalent. SCCmec types II, III, IV, and V were identified in 33.3, 21.3, 23.3, and 21.3% of all isolates, respectively. PVL genes (lukF/S-PV) were detected in 11.3% of all isolates and from 6 CCs (5, 8, 59, 88, 239, and 398). The TSST-1 gene (tst) was detected in 18.0% of the all isolates, predominantly in CC5 (96.3%). All the tst-1-positve CC5 isolates were spa t002. Eighteen patients died within 30 days of hospitalization, and the in-hospital 30-day mortality was 12.0%. Multivariable analysis showed that 60 years old (odds ratio [OR] = 7.2, P = 0.026), cancer diagnosis (OR = 9.6, P = 0.022), and MRSA isolate carriage of tst-1 (OR = 62.5, P < 0.001) were independent factors associated with 30-day mortality. Our study revealed unique MRSA dissemination patterns in our hospital in comparison to those of other regions in China. The finding that tst-1-positive CC5 strains were associated with higher mortality highlights the need for strict infection control measures in order to prevent further spread of these strains in our hospital, as well as others.
Reassessing Conceptual Models of ENSO

AbstractThe complex nature of the El Nino–Southern Oscillation (ENSO) is often simplified through the use of conceptual models, each of which offers a different perspective on the ocean–atmosphere feedbacks underpinning the ENSO cycle. One theory, the unified oscillator, combines a variety of conceptual frameworks in the form of a coupled system of delay differential equations. The system produces a self-sustained oscillation on interannual time scales. While the unified oscillator is assumed to provide a more complete conceptual framework of ENSO behaviors than the models it incorporates, its formulation and performance have not been systematically assessed. This paper investigates the accuracy of the unified oscillator through its ability to replicate the ENSO cycle modeled by flux-forced output from the Australian Community Climate and Earth-System Simulator Ocean Model (ACCESS-OM). The anomalous sea surface temperature equation reproduces the main features of the corresponding tendency modeled by ACCE.