Bacteria-Responsive Self-Assembly of Antimicrobial Peptide Nanonets for Trap-and-Kill of Antibiotic-Resistant Strains

Bacterial trapping using nanonets is a ubiquitous immune defense mechanism against infectious microbes. These nanonets can entrap microbial cells, effectively arresting their dissemination and rendering them more vulnerable to locally secreted microbicides. Inspired by this evolutionarily conserved anti-infective strategy, a series of 15 to 16 residue-long synthetic β-hairpin peptides is herein constructed with the ability to self-assemble into nanonets in response to the presence of bacteria, enabling spatiotemporal control over microbial killing. Using amyloid-specific K114 assay and confocal microscopy, the membrane components lipoteichoic acid and lipopolysaccharide are shown to play a major role in determining the amyloid-nucleating capacity as triggered by Gram-positive and Gram-negative bacteria respectively. These nanonets displayed both trapping and killing functionalities, hence offering a direct improvement from the trap-only biomimetics in literature. By substituting a single turn residue of the non-amyloidogenic BTT1 peptide, the nanonet-forming BTT1-3A analog is produced with comparable antimicrobial potency. With the same sequence manipulation approach, BTT2-4A analog modified from BTT2 peptide showed improved antimicrobial potency against colistin-resistant clinical isolates. The peptide nanonets also demonstrated robust stability against proteolytic degradation, and promising in vivo efficacy and biosafety profile. Overall, these bacteria-responsive peptide nanonets are promising clinical anti-infective alternatives for circumventing antibiotic resistance.     

Iron enhances generation of fibrin fibers in human blood: Implications for pathogenesis of stroke

Stroke is associated with the intracerebral formation of fibrin clots which may lead to irreversible brain damage. Thrombolytic therapies employ a variety of natural and/or recombinant plasminogen activators to initiate fibrinolytic degradation of cerebral thrombi. However, such therapies when installed beyond 4‐ to 6‐h window, may fail to achieve the expected outcome. This is due to the hydroxyl radical‐induced modification of fibrin(ogen) molecules rendering them refractory to fibrinolytic degradation, but no cause of the increased free radical generation in stroke was offered. Here, we show by means of electron microscopy that iron ions added to human blood dramatically enhances fibrin fibers formation with thrombin, and significantly delays fibrinolysis during spontaneous clotting of native blood. Iron ions caused the appearance dense matted fibrin deposits, similar, if not identical, to those observed in plasma of patients with stroke. These results may explain a known relationship between thrombotic diseases and the increased body concentrations of free iron and/or hemoglobin derivatives. We conclude that any action resulting in the inhibition of hemostatic abnormalities, as well as in the reduction of body free iron and scavenging of hydroxyl radicals (e.g., by polyphenols) can potentially prevent pathological reactions associated with consequences of stroke. Microsc. Res. Tech. 75:1185–1190, 2012. © 2012 Wiley Periodicals, Inc.     

Negative emotional and cognitive responses to being unfriended on Facebook: An exploratory study

We consider Facebook unfriending as a form of relationship termination with negative emotional and cognitive consequences. Specifically, ruminative and negative emotional responses are examined via an online survey of adult Facebook users who were unfriended. These responses were positively related to each other and to Facebook intensity. Rumination was positively predicted by using Facebook to connect with existing contacts and was more likely when the unfriender was a close partner. Participants also responded with greater rumination and negative emotion when they knew who unfriended them, when they thought they were unfriended for Facebook-related reasons, and when participants initiated the Facebook friend request. The contribution of these exploratory findings to our growing understanding of negative relational behaviors on Facebook are discussed.     

A longitudinal observational study of the dynamics of Mycoplasma bovis antibodies in naturally exposed and diseased dairy cows

Mycoplasma bovis is an important pathogen causing disease and substantial economic losses in cattle. However, knowledge of the dynamics of antibody responses in individual cows in the face of an outbreak is currently extremely limited. The use of commercial antibody tests to support clinical decision-making and for surveillance purposes is therefore challenging. Our objective was to describe the dynamics of M. bovis antibody responses in 4 Danish dairy herds experiencing an acute outbreak of M. bovis-associated disease, and to compare the antibody dynamics between dairy cows with different disease manifestations. A total of 120 cows were examined using a standardized clinical protocol and categorized into 4 disease groups: “mastitis,” “systemic,” “nonspecific,” and “none.” Paired blood and milk samples were collected and tested using a commercial M. bovis antibody–detecting ELISA. Plots of raw data and generalized additive mixed models with cow and herd as random effects were used to describe serum and milk antibody dynamics relative to the estimated time of onset of clinical disease. Cows with mastitis had high optical density measurement (ODC%) of antibodies in both milk and serum at disease onset. The estimated mean ODC% in milk was below the manufacturer's cut-off for the other groups for the entire study period. The estimated mean serum ODC% in the “systemic” group was high at onset of disease and stayed above the cut-off until 65 d after disease onset. However, the lower 95% confidence interval (CI) for the mean ODC% was only above the manufacturer's cut-off between 7 and 17 d after onset of disease. The CI of the “systemic” and “none” groups did not overlap at any time between the day of disease onset and 65 d after disease onset, and the estimated mean ODC% for both the “nonspecific” and “none” groups were generally below the cut-off for the majority of the study period. In conclusion, the serum antibody responses were highly dynamic and showed a high level of variation between individual cows. This strongly suggests that serology is unlikely to be useful for individual diagnosis of M. bovis-associated disease in dairy cows. However, it might still be useful for herd- or group-level diagnosis. Antibodies in milk were only increased in cows with M. bovis mastitis, indicating that milk antibody measurements only have diagnostic utility for cows with mastitis.     

Group psychotherapy focusing on self-concept change following acquired brain injury: A pilot investigation.

Objective: The current study explored the effectiveness of a group therapy intervention that was focused specifically on self-concept changes following acquired brain injury (ABI). Method: Eighteen individuals in the postacute phase of recovery underwent a 6-week group therapy intervention and were administered a self-concept measure before and after the intervention. Results: Group members showed a significant increase (improvement) in self-concept ratings at the end of the group intervention. Conclusions: Although the results of this study suggest that this intervention may be helpful in improving self-concept following ABI, further exploration is clearly warranted. Future research is needed to investigate the impact of self-concept on emotional adjustment, participation in rehabilitation activities, and functional outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of person and job stereotypes on two personnel decisions.

Two studies investigated whether the effects of incumbent age on personnel decisions are different in a stereotypically older job than in a stereotypically younger job. In Exp I, 19 26–52 yr old managers were asked to make awards recommendations and overall evaluations for 18 hypothetical employees in 3 jobs that varied in age stereotype. Hypothetical employees varied in age and exhibited either a stereotypically older performance pattern or a stereotypically younger pattern of performance. Significant Job?×?Performance Pattern and Target Age?×?Pattern interactions were found in the awards exercises. In Exp II, 19 26–62 yr old managers were asked to make promotion decisions for 18 hypothetical employees in 3 jobs. Again, the Job?×?Pattern interaction was significant. Overall results suggest that when the pattern of performance is inconsistent with the age stereotype of the job, employees receive lower ratings than when behavior is consistent with the job stereotype. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protease-induced aggregation of bovine alpha-lactalbumin: identification of the primary associating fragment

Details in the hydrolysis of alpha-lactalbumin known to result in formation of highly ordered nanotubules, was investigated by incubation of solutions with 10 g alpha-lactalbumin/l with a specific protease from Bacillus licheniformis (BLP). After 50 min of incubation, soluble aggregates were formed, the concentration of which increased until precipitation occurred after 200 min. The latter aggregates were dissolved in urea or at low pH, like the nanotubules characteristic of gels formed by the action of BLP on alpha-lactalbumin at 100 g/l. On the molecular level, alpha-lactalbumin was initially cleaved into two large hydrophobic fragments with masses of 11.6 and 11.3 kDa, which in turn were cleaved in a stepwise manner into the ultimate fragment of 8.8 kDa. This fragment was the predominating component in the insoluble aggregates, and was identified as the sequences 26-37 and 50-113 of alpha-lactalbumin linked together by a disulphide bond. Cleavage of alpha-lactalbumin into this fragment probably created new hydrophobic surfaces and new calcium binding sites allowing its association into ordered structures.     

Analysis of the low molecular weight fraction of serum by LC-dual ESI-FT-ICR mass spectrometry: precision of retention time, mass, and ion abundance

This study quantifies the experimental uncertainty for LC retention time, mass measurement precision, and ion abundance obtained from replicate nLC-dual ESI-FT-ICR analyses of the low molecular weight fraction of serum. We used ultrafiltration to enrich the < 10-kDa fraction of components from the high-abundance proteins in a pooled serum sample derived from ovarian cancer patients. The THRASH algorithm for isotope cluster detection was applied to five replicate nLC-dual ESI-FT-ICR chromatograms. A simple two-level grouping algorithm was applied to the more than 7000 isotope clusters found in each replicate and identified 497 molecular species that appeared in at least four of the replicates. In addition, a representative set of 231 isotope clusters, corresponding to 188 unique molecular species, were manually interpreted to verify the automated algorithm and to set its tolerances. For nLC retention time reproducibility, 95% of the 497 species had a 95% confidence interval of the mean of +/- 0.9 min or less without the use of chromatographic alignment procedures. Furthermore, 95% of the 497 species had a mass measurement precision of < or = 3.2 and < or = 6.3 ppm for internally and externally calibrated spectra, respectively. Moreover, 95% of replicate ion abundance measurements, covering an ion abundance range of approximately 3 orders of magnitude, had a coefficient of variation of less than 62% without using any normalization functions. The variability of ion abundance was independent of LC retention time, mass, and ion abundance quartile. These measures of analytical reproducibility establish a statistical rationale for differentiating healthy and disease patient populations for the elucidation of biomarkers in the low molecular fraction of serum.     

Voces abriendo caminos (voices foraging paths): A qualitative study of the career development of notable Latinas.

This study used qualitative methodology to investigate the career development of 20 notable Latinas. The emergent theory proposed that Latina career development is influenced by sociopolitical, cultural, contextual, and personal variables. Results suggested that (a) career paths tended to be unplanned and nonlinear; (b) background variables, socioeconornic status, and educational experiences influenced the participants' sense of self and career motivation; (c) family, culture, and cultural identity werr influential; (d) relational support systems, particularly those that involved extended family, spouses, and mentors, were important; and (e) the participants' optimism, persistence, passion, and capacity for cognitive reframing helped them cope with challenges and remain true to their values, beliefs, and sense of self. (PsycINFO Database Record (c) 2010 APA, all rights reserved)