Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers

It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects

Cues for Early Social Skills: Direct Gaze Modulates Newborns' Recognition of Talking Faces

Previous studies showed that, from birth, speech and eye gaze are two important cues in guiding early face processing and social cognition. These studies tested the role of each cue independently; however, infants normally perceive speech and eye gaze together. Using a familiarization-test procedure, we first familiarized newborn infants (n = 24) with videos of unfamiliar talking faces with either direct gaze or averted gaze. Newborns were then tested with photographs of the previously seen face and of a new one. The newborns looked longer at the face that previously talked to them, but only in the direct gaze condition. These results highlight the importance of both speech and eye gaze as socio-communicative cues by which infants identify others. They suggest that gaze and infant-directed speech, experienced together, are powerful cues for the development of early social skills

Integration and fusion of standard automated perimetry and optical coherence tomography data for improved automated glaucoma diagnostics

<p>Abstract</p> <p>Background</p> <p>The performance of glaucoma diagnostic systems could be conceivably improved by the integration of functional and structural test measurements that provide relevant and complementary information for reaching a diagnosis. The purpose of this study was to investigate the performance of data fusion methods and techniques for simple combination of Standard Automated Perimetry (SAP) and Optical Coherence Tomography (OCT) data for the diagnosis of glaucoma using Artificial Neural Networks (ANNs).</p> <p>Methods</p> <p>Humphrey 24-2 SITA standard SAP and StratusOCT tests were prospectively collected from a randomly selected population of 125 healthy persons and 135 patients with glaucomatous optic nerve heads and used as input for the ANNs. We tested commercially available standard parameters as well as novel ones (fused OCT and SAP data) that exploit the spatial relationship between visual field areas and sectors of the OCT peripapillary scan circle. We evaluated the performance of these SAP and OCT derived parameters both separately and in combination.</p> <p>Results</p> <p>The diagnostic accuracy from a combination of fused SAP and OCT data (95.39%) was higher than that of the best conventional parameters of either instrument, i.e. SAP Glaucoma Hemifield Test (p < 0.001) and OCT Retinal Nerve Fiber Layer Thickness ≥ 1 quadrant (p = 0.031). Fused OCT and combined fused OCT and SAP data provided similar Area under the Receiver Operating Characteristic Curve (AROC) values of 0.978 that were significantly larger (p = 0.047) compared to ANNs using SAP parameters alone (AROC = 0.945). On the other hand, ANNs based on the OCT parameters (AROC = 0.970) did not perform significantly worse than the ANNs based on the fused or combined forms of input data. The use of fused input increased the number of tests that were correctly classified by both SAP and OCT based ANNs.</p> <p>Conclusions</p> <p>Compared to the use of SAP parameters, input from the combination of fused OCT and SAP parameters, and from fused OCT data, significantly increased the performance of ANNs. Integrating parameters by including a priori relevant information through data fusion may improve ANN classification accuracy compared to currently available methods.</p

The developmental trajectory of attentional orienting to socio-biological cues.

It has been proposed that the orienting of attention in the same direction as another’s point of gaze relies on innate brain mechanisms which are present from birth, but direct evidence relating to the influence of eye gaze cues on attentional orienting in young children is limited. In two experiments, 137 children aged 3–10 years old performed an adapted pro-saccade task with centrally presented uninformative eye gaze, finger pointing and arrow pre-cues which were either congruent or incongruent with the direction of target presentations. When the central cue overlapped with presentation of the peripheral target (Experiment 1), children up to 5 years old had difficulty disengaging fixation from central fixation in order to saccade to the target. This effect was found to be particularly marked for eye gaze cues. When central cues were extinguished simultaneously with peripheral target onset (Experiment 2), this effect was greatly reduced. In both experiments finger pointing cues (image of pointing index finger presented at fixation) exerted a strong influence on saccade reaction time to the peripheral stimulus for the youngest group of children (<5 years). Overall the results suggest that although young children are strongly engaged by centrally presented eye gaze cues, the directional influence of such cues on overt attentional orienting is only present in older children, meaning that the effect is unlikely to be dependent upon an innate brain module. Instead, the results are consistent with the existence of stimulus–response associations which develop with age and environmental experience

Isolation and Mutagenesis of a Capsule-Like Complex (CLC) from Francisella tularensis, and Contribution of the CLC to F. tularensis Virulence in Mice

BACKGROUND: Francisella tularensis is a category-A select agent and is responsible for tularemia in humans and animals. The surface components of F. tularensis that contribute to virulence are not well characterized. An electron-dense capsule has been postulated to be present around F. tularensis based primarily on electron microscopy, but this specific antigen has not been isolated or characterized. METHODS AND FINDINGS: A capsule-like complex (CLC) was effectively extracted from the cell surface of an F. tularensis live vaccine strain (LVS) lacking O-antigen with 0.5% phenol after 10 passages in defined medium broth and growth on defined medium agar for 5 days at 32°C in 7% CO₂. The large molecular size CLC was extracted by enzyme digestion, ethanol precipitation, and ultracentrifugation, and consisted of glucose, galactose, mannose, and Proteinase K-resistant protein. Quantitative reverse transcriptase PCR showed that expression of genes in a putative polysaccharide locus in the LVS genome (FTL_1432 through FTL_1421) was upregulated when CLC expression was enhanced. Open reading frames FTL_1423 and FLT_1422, which have homology to genes encoding for glycosyl transferases, were deleted by allelic exchange, and the resulting mutant after passage in broth (LVSΔ1423/1422_P10) lacked most or all of the CLC, as determined by electron microscopy, and CLC isolation and analysis. Complementation of LVSΔ1423/1422 and subsequent passage in broth restored CLC expression. LVSΔ1423/1422_P10 was attenuated in BALB/c mice inoculated intranasally (IN) and intraperitoneally with greater than 80 times and 270 times the LVS LD₅₀, respectively. Following immunization, mice challenged IN with over 700 times the LD₅₀ of LVS remained healthy and asymptomatic. CONCLUSIONS: Our results indicated that the CLC may be a glycoprotein, FTL_1422 and -FTL_1423 were involved in CLC biosynthesis, the CLC contributed to the virulence of F. tularensis LVS, and a CLC-deficient mutant of LVS can protect mice against challenge with the parent strain

Structural Basis for Type VI Secretion Effector Recognition by a Cognate Immunity Protein

The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three effector proteins, type VI secretion exported 1–3 (Tse1–3), to recipient Gram-negative cells. The Tse2 protein is a cytoplasmic effector that acts as a potent inhibitor of target cell proliferation, thus providing a pronounced fitness advantage for P. aeruginosa donor cells. P. aeruginosa utilizes a dedicated immunity protein, type VI secretion immunity 2 (Tsi2), to protect against endogenous and intercellularly-transferred Tse2. Here we show that Tse2 delivered by the T6SS efficiently induces quiescence, not death, within recipient cells. We demonstrate that despite direct interaction of Tsi2 and Tse2 in the cytoplasm, Tsi2 is dispensable for targeting the toxin to the secretory apparatus. To gain insights into the molecular basis of Tse2 immunity, we solved the 1.00 Å X-ray crystal structure of Tsi2. The structure shows that Tsi2 assembles as a dimer that does not resemble previously characterized immunity or antitoxin proteins. A genetic screen for Tsi2 mutants deficient in Tse2 interaction revealed an acidic patch distal to the Tsi2 homodimer interface that mediates toxin interaction and immunity. Consistent with this finding, we observed that destabilization of the Tsi2 dimer does not impact Tse2 interaction. The molecular insights into Tsi2 structure and function garnered from this study shed light on the mechanisms of T6 effector secretion, and indicate that the Tse2–Tsi2 effector–immunity pair has features distinguishing it from previously characterized toxin–immunity and toxin–antitoxin systems

The Development of Criminal Style in Adolescence and Young Adulthood: Separating the Lemmings from the Loners

Despite broad consensus that most juvenile crimes are committed with peers, many questions regarding developmental and individual differences in criminal style (i.e., co-offending vs. solo offending) remain unanswered. Using prospective 3-year longitudinal data from 937 14- to 17-year-old serious male offenders, the present study investigates whether youths tend to offend alone, in groups, or a combination of the two; whether these patterns change with age; and whether youths who engage in a particular style share distinguishing characteristics. Trajectory analyses examining criminal styles over age revealed that, while most youth evinced both types of offending, two distinct groups emerged: an increasingly solo offender trajectory (83%); and a mixed style offender trajectory (17%). Alternate analyses revealed (5.5%) exclusively solo offenders (i.e., only committed solo offenses over 3 years). There were no significant differences between groups in individuals’ reported number of friends, quality of friendships, or extraversion. However, the increasingly solo and exclusively solo offenders reported more psychosocial maturity, lower rates of anxiety, fewer psychopathic traits, less gang involvement and less self reported offending than mixed style offenders. Findings suggest that increasingly and exclusively solo offenders are not loners, as they are sometimes portrayed, and that exclusively solo offending during adolescence, while rare and previously misunderstood, may not be a risk factor in and of itself

Research into the Health Benefits of Sprint Interval Training Should Focus on Protocols with Fewer and Shorter Sprints

Over the past decade, it has been convincingly shown that regularly performing repeated brief supramaximal cycle sprints (sprint interval training [SIT]) is associated with aerobic adaptations and health benefits similar to or greater than with moderate-intensity continuous training (MICT). SIT is often promoted as a time-efficient exercise strategy, but the most commonly studied SIT protocol (4–6 repeated 30-s Wingate sprints with 4 min recovery, here referred to as ‘classic’ SIT) takes up to approximately 30 min per session. Combined with high associated perceived exertion, this makes classic SIT unsuitable as an alternative/adjunct to current exercise recommendations involving MICT. However, there are no indications that the design of the classic SIT protocol has been based on considerations regarding the lowest number or shortest duration of sprints to optimise time efficiency while retaining the associated health benefits. In recent years, studies have shown that novel SIT protocols with both fewer and shorter sprints are efficacious at improving important risk factors of noncommunicable diseases in sedentary individuals, and provide health benefits that are no worse than those associated with classic SIT. These shorter/easier protocols have the potential to remove many of the common barriers to exercise in the general population. Thus, based on the evidence summarised in this current opinion paper, we propose that there is a need for a fundamental change in focus in SIT research in order to move away from further characterising the classic SIT protocol and towards establishing acceptable and effective protocols that involve minimal sprint durations and repetitions