Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetically introduced hydrogen bond interactions reveal an asymmetric charge distribution on the radical cation of the special-pair chlorophyll P680

The special-pair chlorophyll (Chl) P680 in photosystem II has an extremely high redox potential (Em) to enable water oxidation in photosynthesis. Significant positive-charge localization on one of the Chl constituents, PD1 or PD2, in P680+ has been proposed to contribute to this high Em. To identify the Chl molecule on which the charge is mainly localized, we genetically introduced a hydrogen bond to the 131-keto C=O group of PD1 and PD2 by changing the nearby D1-Val-157 and D2-Val-156 residues to His, respectively. Successful hydrogen bond formation at PD1 and PD2 in the obtained D1-V157H and D2-V156H mutants, respectively, was monitored by detecting 131-keto C=O vibrations in Fourier transfer infrared (FTIR) difference spectra upon oxidation of P680 and the symmetrically located redox-active tyrosines YZ and YD, and they were simulated by quantum-chemical calculations. Analysis of the P680+/P680 FTIR difference spectra of D1-V157H and D2-V156H showed that upon P680+ formation, the 131-keto C=O frequency upshifts by a much larger extent in PD1 (23 cm−1) than in PD2 (<9 cm−1). In addition, thermoluminescence measurements revealed that the D1-V157H mutation increased the Em of P680 to a larger extent than did the D2-V156H mutation. These results, together with the previous results for the mutants of the His ligands of PD1 and PD2, lead to a definite conclusion that a charge is mainly localized to PD1 in P680+.
Association of different adverse life events with distinct patterns of depressive symptoms.

OBJECTIVE The authors sought to determine whether, in a general population sample, different categories of adverse life events were associated with different patterns of depressive symptoms. METHOD A total of 4,856 individuals (53% female) who experienced depressive symptoms in the previous year were assessed in up to four waves over a maximum of 12 years. At each wave, participants reported the severity of 12 symptoms disaggregated from the nine DSM-III-R criteria for major depression and the self-identified cause of these symptoms, which were classified into nine categories of adverse life events. RESULTS The patterns of depressive symptoms associated with the nine categories of adverse life events differed significantly. Deaths of loved ones and romantic breakups were marked by high levels of sadness, anhedonia, appetite loss, and (for romantic breakups) guilt. Chronic stress and, to a lesser degree, failures were associated with fatigue and hypersomnia, but less so with sadness, anhedonia, and appetite loss. Those who reported that no adverse life events caused their dysphoric episodes reported fatigue, appetite gain, and thoughts of self-harm, but less sadness or trouble concentrating. These symptom patterns were found in a between-persons analysis of participants who had a single dysphoric episode, and they were replicated in an independent within-persons analysis of episode-specific symptom deviations among individuals with multiple episodes. Similar results were obtained when the sample was restricted to those meeting DSM-III-R diagnostic criteria for major depression. CONCLUSIONS Depression is a pathoplastic syndrome. Different types of life events are related to different depressive symptom profiles. The results from the within-persons analysis suggest that these relationships are causal.
Clinical significance of preoperative platelet-to-lymphocyte ratio in recurrent hepatocellular carcinoma after thermal ablation: A retrospective analysis

Abstract Purpose: The aim of this study was to elucidate the clinical significance of preoperative Platelet-to-lymphocyte ratio (PLR) in recurrent hepatocellular carcinoma (RHCC) patients after thermal ablation. Materials and methods: We retrospectively reviewed 414 patients with RHCC treated with ultrasound-guided thermal ablation percutaneously between January 2010 and March 2014. The correlation of recurrence-free survival (RFS) with 15 clinical parameters was analysed by Cox multivariate proportional hazard model analysis. The best cut-off value of preoperative PLR was determined with time-dependent receiver operating characteristic (ROC) curve analysis. The value of PLR in predicting recurrence was analysed by Kaplan-Meier. Results: Multivariate Cox proportional hazard model analysis showed that tumour differentiation, prothrombin time (PT), absolute lymphocyte count (ALC) and PLR were risk factors for recurrence in RHCC patients. PLR ≥ 87.87 was considered for evaluation (AUROC = 0.667; P < 0.05), and 166 of 414 patients (40.1%) had PLR of more than 87.87. During the follow-up period (12–52 months), the 1- and 3-year recurrence rates were 39.9% and 54.8% in the low PLR group, which were significantly better than those in the high PLR group (56.0% and 79.5%) (P < 0.05). Kaplan-Meier analysis demonstrated that the RFS in the low PLR group was 45.2% which was significantly higher than that of the high PLR group (20.5%) (X2 = 24.019, P < 0.05). This result suggested that preoperative PLR is a predictor for recurrence followed thermal ablation in RHCC patients, and patients with PLR ≥ 87.87 indicated higher RFS, which may improve the clinical management of RHCC patients. Further studies are warranted to validated this finding and test its clinical applicability in RHCC.
Developmental expression of the potassium current IK,n contributes to maturation of mouse outer hair cells

1 The expression of K+ currents in mouse outer hair cells (OHCs) was investigated as a function of developmental age between postnatal day (P) 0 and P26, using whole‐cell patch clamp. 2 During the first postnatal week, a slow outward K+ current (IK,neo) was expressed by all OHCs from the apical coil of the cochlea. The amplitude of this current increased greatly between P0 and P6. Then, at the beginning of the second postnatal week, IK,neo decreased. At the same time, from P8 onwards, IK,n, a K+ current characteristic of mature OHCs, was rapidly expressed. 3 The expression of IK,n coincided with the onset of electromotility of the cell body of the OHCs, which could also be detected from P8 onwards and increased substantially in size thereafter. 4 I K,n was reversibly blocked by linopirdine, an inhibitor of members of the KCNQ family of K+ channels, with a KD of 0.7 μM. In the cochlea, KCNQ4 is only expressed in OHCs and is responsible for a form of non‐syndromic autosomal dominant deafness. Linopirdine had no effect on other OHC K+ currents at concentrations up to 200 μM. We conclude that ion channels underlying IK,n contain the KCNQ4 subunit. 5 In current clamp, depolarizing current injections from the resting potential triggered action potentials in OHCs during the first postnatal week. Thereafter, more rapid and graded voltage responses occurred from more negative resting potentials. Thus, OHCs mature rapidly from P8 onwards, and IK,n contributes to this maturation.
A Comparison of Algorithms for Retrieving Soil Moisture from ENVISAT/ASAR Images

In this paper, we present an intercomparison of algorithms for retrieving soil moisture content (SMC) from ENVIronmental SATtellite (ENVISAT)/Advanced Synthetic Aperture Radar images. The algorithms taken into consideration were a feedforward artificial neural network (ANN) with two hidden layers, a statistical approach based on Bayes' theorem, and an iterative algorithm based on the nelder-mead direct-search method. The comparison was carried out by using both simulated and experimental data. Simulated data were obtained by means of the integral equation model (IEM). Experimental data were collected in an agricultural area in Northern Italy during 2003-2005; they included backscattering coefficient at HH and HV polarizations and at an incidence angle of thetas = 23deg, as well as detailed ground truth measurements of SMC, surface roughness, and vegetation parameters. HH-polarized data were related to SMC, whereas the information of the cross-polarized channel was used to correct the backscatter for the effects of surface roughness. A comparison of the algorithms with experimental data showed that all the tested approaches produced SMC values that are very close to the measured ones. However, the predictions of the ANN were slightly more suitable than the other methods for generating maps in reasonable time. The production of moisture maps carried out at different dates using this algorithm pointed out the feasibility of separating up to six levels of spatial/temporal variations of SMC in the range of 10%-35%.
Sodium Fluorescein Use During Intraoperative Cystoscopy

BACKGROUND: Indigotindisulfonate sodium has been used during cystoscopy to identify the ureteral meatuses and to verify ureteral efflux during pelvic surgery. The U.S. Food and Drug Administration announced the shortage of indigotindisulfonate sodium in June 2014. Surgeons have since been searching for safe alternatives with comparable visualization and an economically favorable profile. METHOD: The recent shortage of indigotindisulfonate sodium prompted our search for alternative options for visualizing ureteral patency during intraoperative cystoscopy. Multiple methods were considered, including instilling the bladder with D50 water, sterile water, or methylene blue-tinged saline and visualizing the contrast in either viscosity or color of the urine against the instilled medium, preoperative oral phenazopyridine, and intravenous methylene blue. Collectively, these methods proved suboptimal. As an alternative, we injected the 10% preparation of sodium fluorescein at 0.25–1 mL intravenously and observed a brilliant yellow ureteral jet minutes after injection (see Video 1). EXPERIENCE: Ten percent sodium fluorescein given intravenously in doses ranging from 0.25 to 1.0 cc results in good visualization of ureteral jets. One patient experienced transient yellowing of the sclera and palms. CONCLUSION: Sodium fluorescein is an effective alternative to indigotindisulfonate sodium for visualization of ureteral jets during intraoperative cystoscopy.
COPPER AND ANGIOGENESIS: UNRAVELLING A RELATIONSHIP KEY TO CANCER PROGRESSION

1 Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti‐angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive. 2 Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron‐derived X‐rays from third‐generation synchrotrons and the technique of high resolution X‐ray fluorescence microprobe (XFM) analysis. 3 Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of regulatory roles that the spatial dynamics of cellular transition metals may play.
Chronic widespread pain: clinical comorbidities and psychological correlates

Abstract Recent studies have provided consistent evidence for a genetic influence on chronic widespread pain (CWP). The aim of this study was to investigate (1) the etiological structure underlying CWP by examining the covariation between CWP and psychological comorbidities and psychoaffective correlates and (2) the decomposition of the covariation into genetic and environmental components. A total of 3266 female twins (mean age 56.6 years) were subject to multivariate analyses. Using validated questionnaires to classify twins as having CWP, the prevalence of CWP was 20.8%. In the multivariate analysis, the most suitable model was the common pathway model. This model revealed 2 underlying latent variables, one common to anxiety, emotional intelligence, and emotional instability (f1) and the other common to depression and CWP (f2), the latter being highly heritable (86%). Both latent variables (f1 and f2) shared an additive genetic and a nonshared environmental factor. In addition, a second additive genetic factor loading only on f2 was found. This study reveals the structure of genetic and environmental influences of CWP and its psychoaffective correlates. The results show that the clustering of CWP and depression is due to a common, highly heritable, underlying latent trait. In addition, we found evidence that CWP, anxiety, emotional instability, and emotional intelligence are influenced by different underlying latent traits sharing the same genetic and nonshared environmental factors. This is the first study to reveal the structure and relative importance of genetic and environmental influences on complex etiological mechanisms of CWP and its correlates.
Structured-Compressed-Sensing-Based Impulsive Noise Cancelation for MIMO Systems

In this paper, the powerful signal processing theory of structured compressed sensing (SCS) is exploited to overcome the challenge of impulsive noise (IN) cancelation in multiple-input multiple-output (MIMO) systems. To the best of the authors’ knowledge, the SCS theory is adopted for the first time for IN elimination, bridging IN mitigation and MIMO systems for its potential applications in vehicular-related communications. In achieving the SCS-based IN cancelation, the measurements matrix of the IN is first obtained from the null subcarriers in the MIMO system specified by the IEEE 802.11 standards series. The SCS optimization framework is then formulated through the proposed spatially multiple measuring method, by fully exploiting the spatial correlation of the IN signals at different receive antennas. To efficiently reconstruct the IN signal, an enhanced SCS-based greedy algorithm, structured a priori aided sparsity adaptive matching pursuit, is proposed, which significantly improves the accuracy and robustness compared with the state-of-the-art methods. Theoretical analysis is presented to guarantee the convergence and the performance error bound of the proposed greedy algorithm. Computer simulations validate that the proposed scheme outperforms the conventional ones over the wireless MIMO channel.
The function of FOXO1 in the late phases of the cell cycle is suppressed by PLK1-mediated phosphorylation

Polo-like kinase 1 (PLK1) plays crucial roles in multiple stages of cell division. Our previous studies suggest that global transcriptional regulation by PLK1 may contribute to its multiple functions. PLK1 depletion is associated with a decrease in cell viability and the induction of apoptosis; however, the underlying mechanisms are not completely understood. Here, we report that forkhead box protein O1 (FOXO1) is a novel physiological substrate of PLK1. FOXO1 is at the interface of crucial cellular processes, orchestrating programs of gene expression that regulate apoptosis, cell cycle progression, and oxidative-stress resistance. PLK1 interacts with and phosphorylates FOXO1, mainly at the G2/M phase of the cell cycle. PLK1-mediated phosphorylation leads to the impairment of FOXO1’s transcriptional activity in an Akt-independent manner. By immunofluorescence staining and subcellular fractionation, we demonstrate that PLK1-induced FOXO1 phosphorylation causes its nuclear exclusion. Furthermore, PLK1-mediated phosphorylation of FOXO1 negatively regulates its pro-apoptotic function and abrogates its ability to delay entry into and progression through G2/M transition. Therefore, our results suggest that PLK1 abrogates the inhibitory effects of FOXO1 on cell growth and survival to ensure timely cell cycle progression. This study not only reveals a novel and major regulatory mechanism of FOXO1 at the late phases of the cell cycle, but also provides new insight into the molecular mechanisms by which PLK1 inhibition leads to growth arrest and cell death.
The DNA‐methyltransferase inhibitor 5‐aza‐2‐deoxycytidine affects Humicola grisea enzyme activities and the glucose‐mediated gene repression

Humicola grisea var. thermoidea (Hgvt) is a thermophilic ascomycete that produces lignocellulolytic enzymes and it is proposed for the conversion of agricultural residues into useful byproducts. Drugs that inhibit the DNA methyltransferases (DNMTs) activity are employed in epigenetic studies but nothing is known about a possible effect on the production of fungal enzymes. We evaluated the effect of 5‐aza‐2′‐deoxycytidine (5‐Aza; a chemical inhibitor of DNMTs activity) on the secreted enzyme activity and on the transcription of cellulase and xylanase genes from Hgvt grown in agricultural residues and in glucose. Upon cultivation on wheat bran (WB), the drug provoked an increase in the xylanase activity at 96 h. When Hgvt was grown in glucose (GLU), a repressor of Hgvt glycosyl hydrolase genes, 5‐Aza led to increased transcript accumulation for the cellobiohydrolases and for the xyn2 xylanase genes. In WB, 5‐Aza enhanced the expression of the transcription factor CreA gene. Growth on WB or GLU, in presence of 5‐Aza, led to a significant increase in transcripts of the pH‐response regulator PacC gene. To our knowledge, this is the first report on the effect of a DNMT inhibitor in the production of fungal plant cell wall degradation enzymes.
Genetic control of a structural polymer of the Neurospora crassa cell wall

The heteropolysaccharide present in fraction 1 of the Neurospora crassa cell wall has been characterized in wild-type and morphological mutant strains of this fungus. Single and double mutations have been studied to determine possible genetic interactions controlling the chemical composition of such heteropolysaccharides . Single mutations studied were peak-2, scumbo ( FGSC 49), ragged ( FGSC 296), and crisp -1 ( FGSC 488). Double mutations studied were peak-2, scumbo ( FGSC 419), and ragged crisp -1. In all these strains, the main constituents of the heteropolysaccharide were glucose, mannose and galactose. Glycosidic linkages binding these neutral sugars have been identified by gas-liquid chromatography. A chemical structure of fraction I heteropolysaccharide is proposed. The results obtained with double mutants suggest the existence of genetic interactions, such as complementation or additive effects of lesions of different genes, to control the chemical composition and structure of the cell wall and the morphology of N. crassa mycelium.
Two‐dimensional knee valgus displacement as a predictor of patellofemoral pain in adolescent females

Patellofemoral pain (PFP) is a prevalent lower limb musculo‐skeletal injury in adolescent females. Female athletes with PFP display increased frontal plane knee joint motion in comparison to control subjects. The current investigation aimed to determine prospectively whether two‐dimensional knee valgus displacement during landing could predict the risk of developing PFP. Seventy‐six injury‐free adolescent female athletes (age = 12.9 ±0.35 years) participated. At baseline participants performed three drop vertical jump trials from a 31‐cm box. A standard video camera was used to record frontal plane knee joint kinematics. Over the 24‐month follow‐up, eight participants developed PFP, as diagnosed by a Chartered Physiotherapist. Knee valgus displacement was significantly increased in those who developed PFP compared to those who did not (mean difference = 7.79°; P = 0.002; partial eta squared = 0.07). Knee valgus displacement ≥10.6° predicted PFP with a sensitivity of 0.75 and specificity of 0.85. The associated positive likelihood ratio was 5. These results have clinical utility suggesting that two‐dimensional analysis could be implemented to screen for increased risk of PFP in adolescent female athletes.
Genetic heterogeneity in Italian families with familial hemiplegic migraine

Objective: To verify linkage to chromosome 19p13, to detect mutations in the CACNA1A gene, and to correlate genetic results to their clinical phenotypes in Italian families with familial hemiplegic migraine (FHM). Background: FHM is an autosomal dominant disease, classified as a subtype of migraine with aura. Only a proportion of FHM patients have been associated with chromosome 19p13. Among these, four missense mutations within the CACNA1A gene in five unrelated families have been described. Methods: A linkage study was performed in 19 patients affected by FHM from five families by studying microsatellite markers associated with the 19p13 region. All familial and seven additional sporadic patients with FHM were analyzed to search for mutations within the CACNA1A gene by applying the double gradient–denaturant gradient electrophoresis technique. Results: Lod score values did not establish significantly linkage to chromosome 19. However, seven new genetic variants were detected: six were new polymorphisms. The seventh was a missense mutation present in family 1, and it was associated with a hemiplegic migraine phenotype without unconsciousness and cerebellar ataxia. Because this missense mutation is absent in the general population and cosegregates with the disease, it may be a pathologic mutation. Conclusions: Genetic heterogeneity of FHM has been shown in familial and sporadic FHM patients of Italian origin. The new missense mutation—G4644T—is associated with milder clinical features compared with typical FHM.
Recruitment of cortexillin into the cleavage furrow is controlled by Rac1 and IQGAP‐related proteins

Cytokinesis in eukaryotic organisms is under the control of small GTP‐binding proteins, although the underlying molecular mechanisms are not fully understood. Cortexillins are actin‐binding pro teins whose activity is crucial for cytokinesis in Dictyostelium. Here we show that the IQGAP‐related and Rac1‐binding protein DGAP1 specifically interacts with the C‐terminal, actin‐bundling domain of cortexillin I. Like cortexillin I, DGAP1 is enriched in the cortex of interphase cells and translocates to the cleavage furrow during cytokinesis. The activated form of the small GTPase Rac1A recruits DGAP1 into a quaternary complex with cortexillin I and II. In DGAP1− mutants, a complex can still be formed with a second IQGAP‐related protein, GAPA. The simultaneous elimination of DGAP1 and GAPA, however, prevents complex formation and localization of the cortexillins to the cleavage furrow. This leads to a severe defect in cytokinesis, which is similar to that found in cortexillin I/II double‐null mutants. Our observations define a novel and functionally significant signaling pathway that is required for cytokinesis.