Miracle-dz/UniFAR-FTUs huggingface dataset:
Retro-translocation of mitochondrial intermembrane space proteins

Significance Mitochondria contain several hundreds of proteins. The mitochondrial content is regulated by the uptake and degradation of proteins. Stabilization of protein structure by disulfide bonds was proposed to drive protein accumulation in the intermembrane space of mitochondria. However, it remained unknown if structural alterations could lead to protein escape through the physiological barrier formed by the outer mitochondrial membrane. In this work, we present evidence for size-dependent retrograde movement of mitochondrial proteins to the cytosol. We identify the translocase of the outer mitochondrial membrane channel protein Tom40 as an exit route. Our results indicate that the retro-translocation serves as an important surveillance mechanism that regulates the abundance of intermembrane space proteins in response to changes in cellular physiology. The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation. Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding. The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins. Whether the reverse movement of unfolded proteins to the cytosol occurs across the intact outer membrane is unknown. We found that reduced, conformationally destabilized proteins are released from mitochondria in a size-limited manner. We identified the general import pore protein Tom40 as an escape gate. We propose that the mitochondrial proteome is not only regulated by the import and degradation of proteins but also by their retro-translocation to the external cytosolic location. Thus, protein release is a mechanism that contributes to the mitochondrial proteome surveillance.
A Fast Neural Signature of Motivated Attention to Consumer Goods Separates the Sexes

Emotional stimuli guide selective visual attention and receive enhanced processing. Previous event-related potential studies have identified an early (>120 ms) negative potential shift over occipito-temporal regions (early posterior negativity, EPN) presumed to indicate the facilitated processing of survival-relevant stimuli. The present study investigated whether this neural signature of motivated attention is also responsive to the intrinsic significance of man-made objects and consumer goods. To address this issue, we capitalized on gender differences towards specific man-made objects, shoes and motorcycles, for which the Statistical Yearbook 2005 of Germany's Federal Statistical Office (Statistisches Bundesamt, 2005) revealed pronounced differences in consumer behavior. In a passive viewing paradigm, male and female participants viewed pictures of motorcycles and shoes, while their magnetoencephalographic brain responses were measured. Source localization of the magnetic counterpart of the EPN (EPNm) revealed pronounced gender differences in picture processing. Specifically, between 130 and 180 ms, all female participants generated stronger activity in occipito-temporal regions when viewing shoes compared to motorcycles, while all men except one showed stronger activation for motorcycles than shoes. Thus, the EPNm allowed a sex-dimorphic classification of the processing of consumer goods. Self-report data confirmed gender differences in consumer behavior, which, however, were less distinct compared to the brain based measure. Considering the latency of the EPNm, the reflected automatic emotional network activity is most likely not yet affected by higher cognitive functions such as response strategies or social expectancy. Non-invasive functional neuroimaging measures of early brain activity may thus serve as objective measure for individual preferences towards consumer goods.
The Role of Words and Sounds in Infants' Visual Processing: From Overshadowing to Attentional Tuning

Although it is well documented that language plays an important role in cognitive development, there are different views concerning the mechanisms underlying these effects. Some argue that even early in development, effects of words stem from top-down knowledge, whereas others argue that these effects stem from auditory input affecting attention allocated to visual input. Previous research (e.g., Robinson & Sloutsky, 2004a) demonstrated that non-speech sounds attenuate processing of corresponding visual input at 8, 12, and 16 months of age, whereas the current study demonstrates that words attenuate visual processing at 10 months but not at 16 months (Experiment 1). Furthermore, prefamiliarization with non-speech sounds (Experiment 2) resulted in able processing of visual input by 16-month-olds. These findings suggest that some effects of labels found early in development may stem from familiarity with human speech. The possibility of general-auditory factors underlying the effects of words on cognitive development is discussed.
Asymmetric Facial Growth and Deviated Nose: A New Concept

Deviated nose correction is difficult and constitutes a very different issue from septal deviation. When correcting this deformity, traces of asymmetry can be detected. The authors demonstrate facial asymmetry accompanying deviated noses, and such asymmetry is usually ignored by surgeons who typically concentrate only on nose deformities.A total of 5822 pre- and postrhinoplasty photographs related to 547 women and 124 men were reviewed. Out of the total population, the following 3 groups were selected: group A, gross nose and face asymmetry; group B, nose asymmetry with no facial deformity; group C, facial asymmetry with straight nose. Different measurements were applied to the selected photos, presented in Table 1. These included measurement from the lateral canthi to the lateral mouth corners (D1) and from the midface to each most lateral part of the zygomatic arch (D2). Measurements from one side were compared with those from the contralateral side to identify true anatomic differences, as presented in Figure 1.TABLE 1. Selected Groups of PhotosFIGURE 1. Two fixed distances were measured in each photograph and compared with those on the contralateral side.There was a significant difference in the nose and face deformity group, as evidenced by a meaningful difference in both the D1 and D2 measurements.We report a significant growth retardation of the midface and orbit on the concave side of the nose. This impediment may serve as the etiology for many asymmetries of the face and nose.
Resistance of a lowland rain forest to increasing drought intensity in Sabah, Borneo

Occasional strong droughts are an important feature of the climatic environment of tropical rain forest in much of Borneo. This paper compares the response of a lowland dipterocarp forest at Danum, Sabah, in a period of low (LDI) and a period of high (HDI) drought intensity (1986–96, 9.98 y; 1996–99, 2.62 y). Mean annual drought intensity was two-fold higher in the HDI than LDI period (1997 v. 976 mm), and each period had one moderately strong main drought (viz. 1992, 1998). Mortality of ‘all’ trees ≥10 cm gbh (girth at breast height) and stem growth rates of ‘small’ trees 10–<50 cm gbh were measured in sixteen 0.16-ha subplots (half on ridge, half on lower slope sites) within two 4-ha plots. These 10–50-cm trees were composed largely of true understorey species. A new procedure was developed to correct for the effect of differences in length of census interval when comparing tree mortality rates. Mortality rates of small trees declined slightly but not significantly between the LDI and HDI periods (1.53 to 1.48% y−1): mortality of all trees showed a similar pattern. Relative growth rates declined significantly by 23% from LDI to HDI periods (11.1 to 8.6 mm m−1 y−1): for absolute growth rates the decrease was 28% (2.45 to 1.77 mm y−1). Neither mortality nor growth rates were significantly influenced by topography. For small trees, across subplots, absolute growth rate was positively correlated in the LDI period, but negatively correlated in the HDI period, with mortality rate. There was no consistent pattern in the responses among the 19 most abundant species (n≥50 trees) which included a proposed drought-tolerant guild. In terms of tree survival, the forest at Danum was resistant to increasing drought intensity, but showed decreased stem growth attributable to increasing water stress.
Selectivity and Stability via Dendritic Nonlinearity

Inspired by recent studies regarding dendritic computation, we constructed a recurrent neural network model incorporating dendritic lateral inhibition. Our model consists of an input layer and a neuron layer that includes excitatory cells and an inhibitory cell; this inhibitory cell is activated by the pooled activities of all the excitatory cells, and it in turn inhibits each dendritic branch of the excitatory cells that receive excitations from the input layer. Dendritic nonlinear operation consisting of branch-specifically rectified inhibition and saturation is described by imposing nonlinear transfer functions before summation over the branches. In this model with sufficiently strong recurrent excitation, on transiently presenting a stimulus that has a high correlation with feed- forward connections of one of the excitatory cells, the corresponding cell becomes highly active, and the activity is sustained after the stimulus is turned off, whereas all the other excitatory cells continue to have low activities. But on transiently presenting a stimulus that does not have high correlations with feedforward connections of any of the excitatory cells, all the excitatory cells continue to have low activities. Interestingly, such stimulus-selective sustained response is preserved for a wide range of stimulus intensity. We derive an analytical formulation of the model in the limit where individual excitatory cells have an infinite number of dendritic branches and prove the existence of an equilibrium point corresponding to such a balanced low-level activity state as observed in the simulations, whose stability depends solely on the signal-to-noise ratio of the stimulus. We propose this model as a model of stimulus selectivity equipped with self-sustainability and intensity-invariance simultaneously, which was difficult in the conventional competitive neural networks with a similar degree of complexity in their network architecture. We discuss the biological relevance of the model in a general framework of computational neuroscience.
Tuning of EAG K+ channel inactivation: Molecular determinants of amplification by mutations and a small molecule

Ether-à-go-go (EAG) and EAG-related gene (ERG) K+ channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-dependent slow inactivation that is markedly enhanced in rate and extent by 1–10 µM 3-nitro-N-(4-phenoxyphenyl) benzamide, or ICA105574 (ICA). This compound was previously reported to have the opposite effect on ERG1 channels, causing an increase in current magnitude by inhibition of C-type inactivation. The voltage dependence of 2 µM ICA-induced inhibition of EAG1 current was half-maximal at −73 mV, 62 mV negative to the half-point for channel activation. This finding suggests that current inhibition by the drug is mediated by enhanced inactivation and not open-channel block, where the voltage half-points for current inhibition and channel activation are predicted to overlap, as we demonstrate for clofilium and astemizole. The mutation Y464A in the S6 segment also induced inactivation of EAG1, with a time course and voltage dependence similar to that caused by 2 µM ICA. Several Markov models were investigated to describe gating effects induced by multiple concentrations of the drug and the Y464A mutation. Models with the smallest fit error required both closed- and open-state inactivation. Unlike typical C-type inactivation, the rate of Y464A- and ICA-induced inactivation was not decreased by external tetraethylammonium or elevated [K+]e. EAG1 channel inactivation introduced by Y464A was prevented by additional mutation of a nearby residue located in the S5 segment (F359A) or pore helix (L434A), suggesting a tripartite molecular model where interactions between single residues in S5, S6, and the pore helix modulate inactivation of EAG1 channels.
A glance into the uterus during in vitro simulation of embryo transfer.

BACKGROUND The currently low implantation rate after embryo transfer (ET) is partially attributed to technical aspects, such as catheter type, catheter load, placement of catheter tip and physician skills. METHODS Mock ET simulations were conducted with a transparent laboratory model of the uterine cavity. The catheter was loaded with alternating air and coloured liquid media. The transfer procedure was recorded by a digital video camcorder for later analysis. Different sequences of air and liquid volumes, as well as liquids of different viscosity were simulated. RESULTS Injection of liquid with air into the uterus formed an air bubble which blocked the transport of the transferred liquid towards the fundus. The distribution of the transferred matter within the uterine cavity was determined by the composition of the liquid-air sequence and the viscosity ratio between the transferred liquid and the uterine fluid. CONCLUSIONS It is suggested that the catheter load should contain minimal volumes of air in order to enhance the embryos' chances of reaching the site of implantation. The viscosity of the transferred liquid should be as close as possible to that of the uterine fluid in order to avoid transport of embryos towards the cervix.
Morphological Characterization of Mycobacterium tuberculosis

It is more than 100 years since the first Mycobacterium was isolated by Hansen (1874). That was leprosy bacillus, Mycobacterium leprae, which even today is still resisting all attempts to cultivate it in the laboratory. The tubercle bacillus, M. tuberculosis was discovered eight years later by Robert Koch (1882). The Koch discovery was confirmed by more efficient staining models of Ehrlich (1887) and ZiehlNeelsen (1883). Under Light microscope, the tubercle bacilli typically appear as straight or slightly curved rods. According to growth conditions and age of the culture, bacilli may vary in size and shape from coccobacilli to long rods. The dimensions of the bacilli have been reported to be 1-10 μm in length (usually 3-5 μm), and 0.2 -0.6 μm width. The possibility of morphological variations in tubercle bacilli was suggested by few investigators like Malassez and Vignal (1883), Nocard and Roux (1887), Metschnikoff (1888), Lubarsch(1899), Fischel(1893), and Vera and Rettger (1939). They showed under unfavorable conditions, i.e., a limited food supply, or oxygen deprivation, Mycobacterium assumed a swollen appearance without forming the vacuolar or globoid bodies (Vera and Rettger, 1939). These early reports were based on stained preparations and were subjected of severe criticism (Porter and Yegian, 1945). Today with advances in microscopic technique i.e., transmission electron microscope (TEM), scanning electron (SEM) and atomic force microcopy (AFM), almost all of investigators have been agreed that the Koch bacillus does not always manifest itself in the classical rod shape (figure 1). They become shorter in older cultures, filametous within macrophages and ovoid during starvation (Young et al., 2005; Farnia et al., 2010; Shleeva et al., 2011) and they may produce buds (Chauhan et al., 2006) and branches in extensively drug resistance strains (XDR-TB) (Velayati et al 2010; Farnia et al 2010). In the following parts the underlying mechanisms that may help the bacilli to change its morphology was highlighted.
The Hetero-Hexameric Nature of a Chloroplast AAA+ FtsH Protease Contributes to Its Thermodynamic Stability

FtsH is an evolutionary conserved membrane-bound metalloprotease complex. While in most prokaryotes FtsH is encoded by a single gene, multiple FtsH genes are found in eukaryotes. Genetic and biochemical data suggest that the Arabidopsis chloroplast FtsH is a hetero-hexamer. This raises the question why photosynthetic organisms require a heteromeric complex, whereas in most bacteria a homomeric one is sufficient. To gain structural information of the possible complexes, the Arabidopsis FtsH2 (type B) and FtsH5 (type A) were modeled. An in silico study with mixed models of FtsH2/5 suggests that heteromeric hexamer structure with ratio of 4∶2 is more likely to exists. Specifically, calculation of the buried surface area at the interfaces between neighboring subunits revealed that a hetero-complex should be thermodynamically more stable than a homo-hexamer, due to the presence of additional hydrophobic and hydrophilic interactions. To biochemically assess this model, we generated Arabidopsis transgenic plants, expressing epitope-tagged FtsH2 and immuno-purified the protein. Mass-spectrometry analysis showed that FtsH2 is associated with FtsH1, FtsH5 and FtsH8. Interestingly, we found that ‘type B’ subunits (FtsH2 and FtsH8) were 2–3 fold more abundant than ‘type A’ (FtsH1 and FtsH5). The biochemical data corroborate the in silico model and suggest that the thylakoid FtsH hexamer is composed of two ‘type A’ and four ‘type B’ subunits.
Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes.

OBJECTIVE Intra-amniotic inflammation is a major determinant of maternal and neonatal outcome in patients with preterm labor. Matrix metalloproteinase-8 is a sensitive marker of inflammation in body fluids. This study was conducted to examine the value of amniotic fluid matrix metalloproteinase-8 determinations in patients with preterm labor and intact membranes. STUDY DESIGN Amniotic fluid was obtained by transabdominal amniocentesis from 371 patients with preterm labor. Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain examination, white blood cell count, and matrix metalloproteinase-8 (enzyme-linked immunosorbent assay) determination. Nonparametric statistics were used for analysis. RESULTS The rate of preterm delivery was 54% (200/371) and that of intra-amniotic infection was 9.2% (34/371). The median amniotic fluid matrix metalloproteinase-8 concentration was more than 50-fold higher in patients with intra-amniotic infection than in patients with no intra-amniotic infection (median, 605.6 ng/mL; range, 0.65-15,000 ng/mL vs median, 10.6 ng/mL; range, <0.06-16,600 ng/mL, respectively; P <.0001). The matrix metalloproteinase-8 amniotic fluid concentrations were significantly higher in patients who delivered preterm than in patients who delivered at term (median, 19.5 ng/mL; range, <0.06-16,600 ng/mL vs median, 2.1 ng/mL; range, <0.06-500 ng/mL, respectively; P <.001). After exclusion of patients with intra-amniotic infection, patients who delivered preterm had a significantly higher median amniotic fluid matrix metalloproteinase-8 than patients who delivered at term (P <.05). An amniotic fluid matrix metalloproteinase-8 level of >30 ng/mL was an independent predictor for the occurrence of neonatal morbidity (odds ratio, 3.4; 95% CI, 1.9-5.8; P <.01). CONCLUSION Increased amniotic fluid matrix metalloproteinase-8 concentrations identify patients at risk for intra-amniotic infection, impending preterm delivery, and adverse neonatal outcome.
The dark matter haloes of massive, relaxed galaxy clusters observed with Chandra

We use the Chandra X-ray Observatory to study the dark matter halos of 34 massive, dynamically relaxed galaxy clusters, spanning the redshift range 0.06 < z < 0.7. The observed dark matter and total mass (dark-plus-luminous matter) profiles can be approximated by the Navarro Frenk & White (hereafter NFW) model for cold dark matter (CDM) halos; for {approx} 80 percent of the clusters, the NFW model provides a statistically acceptable fit. In contrast, the singular isothermal sphere model can, in almost every case, be completely ruled out. We observe a well-defined mass-concentration relation for the clusters with a normalization and intrinsic scatter in good agreement with the predictions from simulations. The slope of the mass-concentration relation, c {infinity} M{sub vir}{sup a}/(1 + z){sup b} with a = -0.41 {+-} 0.11 at 95 percent confidence, is steeper than the value a {approx} -0.1 predicted by CDM simulations for lower mass halos. With the slope a included as a free fit parameter, the redshift evolution of the concentration parameter, b = 0.54 {+-} 0.47 at 95 percent confidence, is also slower than, but marginally consistent with, the same simulations (b {approx} 1). Fixing a {approx} -0.1 leads to an apparent evolution that is significantly slower, b = 0.20 {+-} 0.45, although the goodness of fit in this case is significantly worse. Using a generalized NFW model, we find the inner dark matter density slope, a, to be consistent with unity at 95 percent confidence for the majority of clusters. Combining the results for all clusters for which the generalized NFW model provides a good description of the data, we measure ? = 0.88 {+-} 0.29 at 95 percent confidence, in agreement with CDM model predictions.
Top and Higgs flavor changing neutral couplings in two Higgs doublets model

We study various channels of top and Higgs flavor changing neutral couplings in the two Higgs doublet model with natural flavor conservation (2HDM-I and 2HDM-II). We update known results about $t\ensuremath{\rightarrow}c\ensuremath{\gamma},cZ,cg$ and comment on $t\ensuremath{\rightarrow}c{h}^{0}$. The decays $t\ensuremath{\rightarrow}c{h}^{0}$ as well as ${{h}^{0},{H}^{0}}\ensuremath{\rightarrow}\overline{t}c$ are sensitive both to the bottom Yukawa coupling as well as to the trilinear scalar couplings ${h}^{0}{H}^{+}{H}^{\ensuremath{-}}$ and ${H}^{0}{H}^{+}{H}^{\ensuremath{-}}$. After imposing unitarity constraints as well as vacuum stability conditions on scalar sector parameters, in 2HDM-II we found that for large $\mathrm{tan}﻿\ensuremath{\beta}\ensuremath{\gtrsim}40$ and rather light charged Higgs mass ${M}_{H\ifmmode\pm\else\textpm\fi{}}\ensuremath{\gtrsim}150\text{ }\text{ }\mathrm{GeV}$, the maximum values allowed for $\mathrm{Br}(t\ensuremath{\rightarrow}c{h}^{0})$, $\mathrm{Br}({H}^{0}\ensuremath{\rightarrow}\overline{t}c)$, and $\mathrm{Br}({h}^{0}\ensuremath{\rightarrow}\overline{t}c)$ are: $8\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$, ${10}^{\ensuremath{-}3}$, and ${10}^{\ensuremath{-}4}$ respectively. For charged Higgs mass in the range $[200,300]\text{ }\text{ }\mathrm{GeV}$, which can accommodate $B\ensuremath{\rightarrow}{X}_{s}\ensuremath{\gamma}$ constraint if one takes into account large theoretical uncertainties, the branching ratio of both ${H}^{0}\ensuremath{\rightarrow}\overline{t}c$ and ${h}^{0}\ensuremath{\rightarrow}\overline{t}c$ can still be slightly larger than ${10}^{\ensuremath{-}5}$. For ${A}^{0}\ensuremath{\rightarrow}\overline{t}c$, its branching ratio is smaller than $\ensuremath{\approx}{10}^{\ensuremath{-}7}$ in both 2HDM-I and 2HDM-II. We study also the top-charm associated production at ${e}^{+}{e}^{\ensuremath{-}}$ colliders and its $\ensuremath{\gamma}\ensuremath{\gamma}$ option as well as at muon colliders. It is found that the cross section of $\ensuremath{\gamma}\ensuremath{\gamma}\ensuremath{\rightarrow}\overline{t}c$ can be of the order $0.01\ensuremath{\rightarrow}0.1\text{ }\text{ }\mathrm{fb}$ near threshold region, while the cross section of ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}\overline{t}c$ is well below ${10}^{\ensuremath{-}2}\text{ }\text{ }\mathrm{fb}$. The situation is slightly better for muon colliders where a few fb cross section can be reached for large $\mathrm{tan}﻿\ensuremath{\beta}$ and low center-of-mass energy $\sqrt{s}\ensuremath{\lesssim}500\text{ }\text{ }\mathrm{GeV}$.