Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetics of DNA uptake during transformation provide evidence for a translocation ratchet mechanism

Significance Transport of macromolecules through nanometer-sized membrane pores is a ubiquitous theme in cell biology. Examples include the linear import of precurser proteins into mitochondria and DNA transport during bacterial gene transfer. However, little is known about the biophysical mechanisms that bias the direction of macromolecular movement within membrane pores. Here, we used a single-molecule approach for studying a key step of bacterial gene transfer, the import of macromolecular DNA from the environment into the periplasm of the bacterial pathogen Neisseria gonorrhoeae. We show that the force-dependent kinetics of DNA uptake are in remarkable agreement with a translocation ratchet model, whereby the periplasmic ComE protein acts as a chaperone that rectifies DNA diffusion through the outer membrane by reversible binding. Horizontal gene transfer can speed up adaptive evolution and support chromosomal DNA repair. A particularly widespread mechanism of gene transfer is transformation. The initial step to transformation, namely the uptake of DNA from the environment, is supported by the type IV pilus system in most species. However, the molecular mechanism of DNA uptake remains elusive. Here, we used single-molecule techniques for characterizing the force-dependent velocity of DNA uptake by Neisseria gonorrhoeae. We found that the DNA uptake velocity depends on the concentration of the periplasmic DNA-binding protein ComE, indicating that ComE is directly involved in the uptake process. The velocity–force relation of DNA uptake is in very good agreement with a translocation ratchet model where binding of chaperones in the periplasm biases DNA diffusion through a membrane pore in the direction of uptake. The model yields a speed of DNA uptake of 900 bp⋅s−1 and a reversal force of 17 pN. Moreover, by comparing the velocity–force relation of DNA uptake and type IV pilus retraction, we can exclude pilus retraction as a mechanism for DNA uptake. In conclusion, our data strongly support the model of a translocation ratchet with ComE acting as a ratcheting chaperone.
MEG Responses to the Perception of Global Structure within Glass Patterns

Background The perception of global form requires integration of local visual cues across space and is the foundation for object recognition. Here we used magnetoencephalography (MEG) to study the location and time course of neuronal activity associated with the perception of global structure from local image features. To minimize neuronal activity to low-level stimulus properties, such as luminance and contrast, the local image features were held constant during all phases of the MEG recording. This allowed us to assess the relative importance of striate (V1) versus extrastriate cortex in global form perception. Methodology/Principal Findings Stimuli were horizontal, rotational and radial Glass patterns. Glass patterns without coherent structure were viewed during the baseline period to ensure neuronal responses reflected perception of structure and not changes in local image features. The spatial distribution of task-related changes in source power was mapped using Synthetic Aperture Magnetometry (SAM), and the time course of activity within areas of maximal power change was determined by calculating time-frequency plots using a Hilbert transform. For six out of eight observers, passive viewing of global structure was associated with a reduction in 10–20 Hz cortical oscillatory power within extrastriate occipital cortex. The location of greatest power change was the same for each pattern type, being close to or within visual area V3a. No peaks of activity were observed in area V1. Time-frequency analyses indicated that neural activity was least for horizontal patterns. Conclusions We conclude: (i) visual area V3a is involved in the analysis of global form; (ii) the neural signature for perception of structure, as assessed using MEG, is a reduction in 10–20 Hz oscillatory power; (iii) different neural processes may underlie the perception of horizontal as opposed to radial or rotational structure; and (iv) area V1 is not strongly activated by global form in Glass patterns.
PRIS: A multiple-item scale for measuring perceived risk of Internet shopping

The purpose of this study is to report the development of a scale to measure perceived risk associated with online shopping. This research identified a model of perceived risks consisting of four components: financial risk, product performance risk, time/convenience risk and privacy/security risk. Exploratory and confirmatory factor analyses were used, and convergent and discriminant validity were assessed in the scale development procedures to support the Perceived Risk of Internet Shopping (PRIS) scale as a reliable and valid instrument. Nomological net constructed for the validity of PRIS scale empirically supported the relationships among perceived risk, familiarity and knowledge of Internet and computer, Internet experience, prior remote shopping behavior, trust in-e-store, and domain-specific innovativeness. This PRIS scale will contribute to the investigation and understanding of the nature and consequences of perceived risk in the online shopping environment. It provides a reliable and wellvalidated scale to compare the academic studies and move the research forward.
Compensatory T-Cell Regulation in Unaffected Relatives of SLE Patients, and Opposite IL-2/CD25-Mediated Effects Suggested by Coreferentiality Modeling

In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4+CD25bright T-cells that were regularly 70–90% Foxp3+. We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.
Extraction of honey from underground bee nests by central African chimpanzees (Pan troglodytes troglodytes) in Loango National Park, Gabon: Techniques and individual differences

A detailed analysis of tool use behaviors can disclose the underlying cognitive traits of the users. We investigated the technique used by wild chimpanzees to extract the underground nests of stingless bees (Meliplebeia lendliana), which represent a hard‐to‐reach resource given their highly undetectable location. Using remote‐sensor camera trap footage, we analyzed 151 visits to 50 different bee nests by 18 adult chimpanzees of both sexes. We quantified the degree of complexity and flexibility of this technique by looking at the behavioral repertoire and at its structural organization. We used Generalized Linear Mixed Models to test whether individuals differed in their action repertoire sizes and in their action sequencing patterns, as well as in their preferences of use of different behavioral elements (namely, actions, and grip types). We found that subjects showed non‐randomly organized sequences of actions and that the occurrence of certain actions was predicted by the type of the previous action in the sequences. Subjects did not differ in their repertoire sizes, and all used extractive actions involving tools more often than manual digging. As for the type of grip employed, the grip involving the coordinated use of hands and feet together was most frequently used by all subjects when perforating, and we detected significant individual preferences in this domain. Overall, we describe a highly complex and flexible extractive technique, and propose the existence of inter‐individual variation in it. We discuss our results in the light of the evolution of higher cognitive abilities in the human lineage.
The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Yersinia pseudotuberculosis is a Gram-negative bacterium and zoonotic pathogen responsible for a wide range of diseases, ranging from mild diarrhea, enterocolitis, lymphatic adenitis to persistent local inflammation. The Y. pseudotuberculosis invasin D (InvD) molecule belongs to the invasin (InvA)-type autotransporter proteins, but its structure and function remain unknown. In this study, we present the first crystal structure of InvD, analyzed its expression and function in a murine infection model, and identified its target molecule in the host. We found that InvD is induced at 37 °C and expressed in vivo 2–4 days after infection, indicating that InvD is a virulence factor. During infection, InvD was expressed in all parts of the intestinal tract, but not in deeper lymphoid tissues. The crystal structure of the C-terminal adhesion domain of InvD revealed a distinct Ig-related fold that, apart from the canonical β-sheets, comprises various modifications of and insertions into the Ig-core structure. We identified the Fab fragment of host-derived IgG/IgA antibodies as the target of the adhesion domain. Phage display panning and flow cytometry data further revealed that InvD exhibits a preferential binding specificity toward antibodies with VH3/VK1 variable domains and that it is specifically recruited to a subset of B cells. This finding suggests that InvD modulates Ig functions in the intestine and affects direct interactions with a subset of cell surface-exposed B-cell receptors. In summary, our results provide extensive insights into the structure of InvD and its specific interaction with the target molecule in the host.
Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology

Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of serious neonatal infections. GBS is an opportunistic commensal constituting a part of the intestinal and vaginal physiologic flora and maternal colonization is the principal route of GBS transmission. GBS is a pathobiont that converts from the asymptomatic mucosal carriage state to a major bacterial pathogen causing severe invasive infections. At present, as many as 10 serotypes (Ia, Ib, and II–IX) are recognized. The aim of the current review is to shed new light on the latest epidemiological data and clonal distribution of GBS in addition to discussing the most important colonization determinants at a molecular level. The distribution and predominance of certain serotypes is susceptible to variations and can change over time. With the availability of multilocus sequence typing scheme (MLST) data, it became clear that GBS strains of certain clonal complexes possess a higher potential to cause invasive disease, while other harbor mainly colonizing strains. Colonization and persistence in different host niches is dependent on the adherence capacity of GBS to host cells and tissues. Bacterial biofilms represent well-known virulence factors with a vital role in persistence and chronic infections. In addition, GBS colonization, persistence, translocation, and invasion of host barriers are largely dependent on their adherence abilities to host cells and extracellular matrix proteins (ECM). Major adhesins mediating GBS interaction with host cells include the fibrinogen-binding proteins (Fbs), the laminin-binding protein (Lmb), the group B streptococcal C5a peptidase (ScpB), the streptococcal fibronectin binding protein A (SfbA), the GBS immunogenic bacterial adhesin (BibA), and the hypervirulent adhesin (HvgA). These adhesins facilitate persistent and intimate contacts between the bacterial cell and the host, while global virulence regulators play a major role in the transition to invasive infections. This review combines for first time epidemiological data with data on adherence and colonization for GBS. Investigating the epidemiology along with understanding the determinants of mucosal colonization and the development of invasive disease at a molecular level is therefore important for the development of strategies to prevent invasive GBS disease worldwide.
Higher prevalence and increased severity of sleep‐disordered breathing in male patients with chronic tinnitus: Our experience with 173 cases

Tinnitus and sleep are closely related. One of the most important aspects of tinnitus is its association with sleep disturbance. According to the literature, up to 71% of patients with tinnitus report sleep problems (1); furthermore, insomnia is also associated with more distressing tinnitus (2). Conversely, sleep disturbance was proposed as one of the causes of chronic tinnitus (3). The relationship of tinnitus with sleep-disordered breathing (SDB) and obstructive sleep apnea (OSAS) has rarely been mentioned (4). In a recent population-based case-control study, the risk of tinnitus was found to increase 1.36 times in patients with OSAS. However, no detailed grading or severity of SDB (or OSAS) and tinnitus was provided. The purpose of this study was to investigate the exact relationship between tinnitus and SDB and delineate the incidence and severity of SDB in patients with chronic tinnitus; moreover, our study reports the preliminary outcome of tinnitus after intervention with continuous positive airway pressure (CPAP) in selected patients with moderate to severe SDB. This article is protected by copyright. All rights reserved.
Biological variation and diagnostic accuracy of dehydration assessment markers.

BACKGROUND Well-recognized markers for static (one time) or dynamic (monitoring over time) dehydration assessment have not been rigorously tested for their usefulness in clinical, military, and sports medicine communities. OBJECTIVE This study evaluated the components of biological variation and the accuracy of potential markers in plasma, urine, saliva, and body mass (B(m)) for static and dynamic dehydration assessment. DESIGN We studied 18 healthy volunteers (13 men and 5 women) while carefully controlling hydration and numerous preanalytic factors. Biological variation was determined over 3 consecutive days by using published methods. Atypical values based on statistical deviations from a homeostatic set point were examined. Measured deviations in body fluid were produced by using a separate, prospective dehydration experiment and evaluated by receiver operating characteristic (ROC) analysis to quantify diagnostic accuracy. RESULTS All dehydration markers displayed substantial individuality and one-half of the dehydration markers displayed marked heterogeneity of intraindividual variation. Decision levels for all dehydration markers were within one SD of the ROC criterion values, and most levels were nearly identical to the prospective group means after volunteers were dehydrated by 1.8-7.0% of B(m). However, only plasma osmolality (P(osm)) showed statistical promise for use in the static dehydration assessment. A diagnostic decision level of 301 plusmn 5 mmol/kg was proposed. Reference change values of 9 mmol/kg (P(osm)), 0.010 [urine specific gravity (U(sg))], and 2.5% change in B(m) were also statistically valid for dynamic dehydration assessment at the 95% probability level. CONCLUSIONS P(osm) is the only useful marker for static dehydration assessment. P(osm), U(sg), and B(m) are valid markers in the setting of dynamic dehydration assessment.
Cloning of a Novel Protein Interacting with BRS-3 and Its Effects in Wound Repair of Bronchial Epithelial Cells

Bombesin receptor subtype 3 (BRS-3), the orphan bombesin receptor, may play a role in the regulation of stress responses in lung and airway epithelia. Bombesin receptor activated protein (BRAP )is a novel protein we found in our previous study which interacts with BRS-3. This study was designed to observe the subcellular location and wound repair function of BRAP in human bronchial epithelial cells (HBECs). BRAP ORF was amplified by RT-PCR and ligated to pEGFP-C1 vector, and then the recombinant plasmid pEGFP-C1-BRAP was transfected into Hela cells. The location of BRAP protein was observed by laser confocal microscope, and the expression of it was analyzed by Western-blot. At the same time,we built the recombinant plasmid pcDNA3.1(+)-BRAP, transfected it into HBECs and observed its impact on cell cycle and wound repair of HBECs. The results showed that BRAP locates in membrane and cytoplasm and increases significantly in transfected cells. Flow cytometry results demonstrated that the recombinant plasmid increases S phase plus G2 phase of cell cycle by 25%. Microscopic video analysis system showed that the repair index of wounded HBECs increases by 20% through stable expression of BRAP. The present study demonstrated that BRAP locates in the membrane and cytoplasm, suggesting that this protein is a cytoplasm protein, which promotes cell cycle and wound repair of HBECs.
The effect of dispersal on rates of cumulative cultural evolution

The ability to develop cultural adaptations to local environments is critical to the biological success of humans. Although overall population size and connectedness are thought to play an important role in increasing the rate of cumulative cultural evolution, the independent effect of dispersal rules on rates of cultural evolution has not been examined. Here, a computational model is used to explore the effect of dispersal on the rate of cultural evolution in traits transmitted patrilineally (from father to son), matrilineally (mother to daughter) and bilineally (through both sexes). Two dispersal conditions are modelled: patrilocality (where females disperse and males stay) and bilocality (where either sex may disperse). The results suggest that when only females disperse, the capacity for cumulative cultural evolution in traits shared only among males is severely constrained. This occurs even though overall rates of dispersal and the number of cultural models available to males and females are identical in both dispersal conditions. The constraints on the evolution of patrilineally inherited traits could be considered to represent a process of ‘cultural inbreeding', analogous to genetic inbreeding.
Exploring the Connection Between Self-Efficacy and Effective Diabetes Self-f Management

PURPOSE the purpose of this study was to review the existing empirical evidence about factors that contribute to effective diabetes self-management as indicated by healthy outcomes in persons with the disease, with a specific focus on self-efficacy, to determine the link between learned self-efficacy and effective diabetes self-management in adults. METHODS A systematic review was conducted of the extant literature from 1985-2001 that described factors related to effective self-management of diabetes. The review included theoretical and empirical articles. The search engines included CINAHL, MEDLINE, PUBMED, and COCHRANE. RESULTS Empirical evidence supports the following factors to improve the education outcomes for adults with diabetes: involve people with diabetes in their own care, guide them in actively learning about the disease, explore their feelings about having the disease, and teach them the skills necessary to adjust their behavior to control their own health outcomes. Thus, the goal for educating people with diabetes is to improve their individual self-efficacy and, accordingly, their self-management ability. CONCLUSIONS Education sessions need to involve fewer lectures and more practical, interactive exercises that focus on developing specific skills. Follow-up contact is a valuable method for helping people make a healthy adjustment to living with diabetes.
Remote Ischemic Postconditioning Improves Myocardial Dysfunction Via the Risk and Safe Pathways in a Rat Model of Severe Hemorrhagic Shock

Introduction: Patients who have been resuscitated after severe hemorrhagic shock still have a high mortality rate. Previously published literature has suggested that remote ischemic postconditioning (RIPostC) has a cardioprotective effect, but few studies have focused on RIPostC performed after severe hemorrhagic shock. In this study, we aim to explore the effects and mechanism of RIPostC on myocardial ischemia and reperfusion injuries after hemorrhagic shock. Methods: Fifty male rats were randomized into four groups: sham, control, remote ischemic per-conditioning (RIPerC), and RIPostC. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume. Remote ischemic conditioning (RIC) was induced by four cycles of limb ischemia for 5 min followed by 5 min of reperfusion, during and after resuscitation for the RIPerC and RIPostC groups, respectively. Myocardial function, survival rate, IL-6, IL-10, and SOD were detected. Myocardial damage was histopathologically analyzed, and proteins related to the reperfusion injury salvage kinase (RISK) pathway (Akt, MEK, ERK1/2) and the survival activating factor enhancement (SAFE) pathway (STAT-3 and STAT5) were measured. Results: Compared with the control group, the ejection fraction and myocardial performance indexes were significantly better in both RIC groups 2 h after resuscitation. Myocardial damage was attenuated and survival time increased significantly in the RIC groups. IL-6 and cardiac troponin I (cTnI) levels were notably reduced in both RIC groups. Only RIPostC had significantly increased levels of SOD and IL-10. The SAFE and RISK pathways were activated by RIPostC, whereas the effect of RIPerC was not significant. Conclusions: RIPostC attenuated myocardial dysfunction and survival outcomes via the activation of the SAFE and RISK pathways in this rat model of hemorrhagic shock. RIPerC improves myocardial dysfunction, but might not do so via the SAFE and RISK pathways.