A Secondary Metabolic Enzyme Functioned as an Evolutionary Seed of a Primary Metabolic Enzyme.

The antibiotic alaremycin has a structure that resembles that of 5-aminolevulinic acid (ALA), a universal precursor of porphyrins, and inhibits porphyrin biosynthesis. Genome sequencing of the alaremycin-producing bacterial strain and enzymatic analysis revealed that the first step of alaremcyin biosynthesis is catalysed by the enzyme, AlmA, which exhibits a high degree of similarity to 5-aminolevulinate synthase (ALAS) expressed by animals, protozoa, fungi, and α-proteobacteria. Site-directed mutagenesis of AlmA revealed that the substitution of two amino acids residues around the substrate binding pocket transformed its substrate specificity from that of alaremycin precursor synthesis to ALA synthesis. To estimate the evolutionary trajectory of AlmA and ALAS, we performed an ancestral sequence reconstitution analysis based on a phylogenetic tree of AlmA and ALAS. The reconstructed common ancestral enzyme of AlmA and ALAS exhibited alaremycin precursor synthetic activity, rather than ALA synthetic activity. These results suggest that ALAS evolved from an AlmA-like enzyme. We propose a new evolutionary hypothesis in which a non-essential secondary metabolic enzyme acts as an 'evolutionary seed' to generate an essential primary metabolic enzyme.

Ketamine Does Not Change Natural Killer Cell Cytotoxicity in Patients Undergoing Cancer Surgery: Basic Experiment and Clinical Trial.

Background: The natural killer cell cytotoxicity (NKCC) suppressed by nociceptive stimuli, systemic inflammation, and drugs used during cancer surgery may be associated with poor outcomes. We investigated the potential modulation of ketamine on NKCC in vitro and in a clinical setting during cancer surgery. Subjects and Methods. The NK cell line KHYG1 was cultured for the in vitro experiments. The NK cells were treated with 3 and 10 µM ketamine (the ketamine groups) or without ketamine (the control) for 4, 24, and 48 h. The posttreatment NKCC was measured with a lactate dehydrogenase assay and compared among the treatment groups. For the clinical study, lung cancer patients (n = 38) and prostate cancer patients (n = 60) who underwent radical cancer surgeries at a teaching hospital were recruited. The patients received propofol and remifentanil superposed with or without ketamine (ketamine group, n = 47; control group, n = 51). The primary outcome was the difference in NKCC between these groups. Results: In the in vitro experiment, the cytotoxicity of NK cells was similar with or without ketamine at all of the incubation periods. The patients' NKCC was also not significantly different between the patients who received ketamine and those who did not, at the baseline (36.6 ± 16.7% vs. 38.5 ± 15.4%, p = 0.56) and at 24 h (25.6 ± 12.9% vs. 27.7 ± 13.5%, respectively, p = 0.49). Conclusion: Ketamine does not change NKCC in vitro or in the clinical setting of patients who undergo cancer surgery. This trial is registered with UMIN000021231.

Response inhibition deficits are positively associated with trait rumination, but attentional inhibition deficits are not: aggressive behaviors and interpersonal stressors as mediators.

Previous findings on relationships between inhibition that is a core executive function, and trait rumination have been inconsistent. This inconsistency could be overcome by investigating the association between rumination and the two subcomponents of inhibition: response inhibition and attentional inhibition. This study examined whether and how response inhibition and attentional inhibition were related to rumination as well as worry. University students in Japan (N = 213) conducted the Go/No-Go Task and the Modified Stroop Task. They also completed self-report measures of depression, trait rumination, trait worry, stressors, and aggressive behaviors. Results indicated that response inhibition deficits were positively associated with trait rumination, and this association was mediated by increases in aggressive behaviors and interpersonal stressors. The associations between these variables remained significant even after controlling for depression level. There were no significant direct or indirect associations between attentional inhibition deficits and rumination. These results suggest that response inhibition deficits, among the subcomponents of inhibition, have an indirect positive association with rumination through interpersonal processes. Results also showed nonsignificant differences between rumination and worry in the magnitude of correlation coefficients with the two subcomponents of inhibition. Therefore, it remains unclear whether the positive association with response inhibition is unique to rumination.

Repeated retrieval of generalized memories can impair specific autobiographical recall: A retrieval induced forgetting account.

Overgeneral autobiographical memory (OGM) refers to the tendency toward increased general memory and reduced specific memory recall, observed in various psychiatric disorders. Previous studies have suggested that inhibitory processes involved in resolving competition between competing memories may reduce memory specificity via retrieval-induced forgetting (RIF). However, it remains unclear whether the repeated retrieval of general memories can induce forgetting of specific memories. We adapted the RIF paradigm to address this question across three experiments. Participants first generated specific memories in response to positively and negatively valenced cue words. They then generated and repeatedly retrieved general memories for half of the cue words. Recall for all of the original specific memories was later tested. Experiment 1 showed that the retrieval practice of general memories reduced the recall of associated specific memories, regardless of cue valence. Experiment 2 demonstrated that this forgetting effect was cue independent, occurring even when novel retrieval cues were used on the final test. Experiment 3 suggested that this effect was competition dependent, finding a greater RIF effect following practice of general memories (high competition) than following a cue-color association task (low competition). These results suggest that repeated retrieval of general memories suppressed specific memory representations through RIF. These findings are discussed in relation to hierarchical models of autobiographical memory, mechanisms that maintain overgeneral memory tendencies, and the role of retrieval in shaping autobiographical memory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Do shorter inter-stimulus intervals in the go/no-go task enable better assessment of response inhibition?

Young, Sutherland, and McCoy indicated that a Go/No-Go Task (GNG) becomes more difficult as the inter-stimulus intervals (ISIs) becomes shorter. However, is the number of commission errors under extremely short ISIs a useful metric for assessing response inhibition? This study challenges the assumption that a shorter ISI in the GNG enables better assessment of response inhibition. University students (N = 213) completed the GNG, the Conners Continuous Performance Test 3rd Edition (CCPT), and the Modified Stroop Task. The GNG comprised four blocks of 400, 600, 800, and 1000 ms ISIs, whereas the stimulus presentation was fixed at 250 ms. Consistent with Young et al., shorter ISIs in the GNG resulted in more commission errors. In the block with the shortest ISI, participants also failed more frequently in responses in go trials than in the other blocks, which appears to increase in error variance of commission errors. Consistent with this interpretation, the association between the number of commission errors in the block with 400 ms ISI and CCPT performance was weaker than those between the number of commission errors in other blocks and CCPT performance. It is concluded that using the number of commission errors in the condition with extremely short ISIs in the GNG might be inappropriate for assessing response inhibition.

Immunomodulation by ketamine as an adjunct to total intravenous anesthesia in patients undergoing minimally invasive radical prostatectomy: A randomized pilot trial.

Post-surgery immunomodulation, including reduced natural killer cell cytotoxicity (NKCC), is recognized as a predictor of poor outcomes in patients following cancer surgery. The present study investigated direct immunomodulation via ketamine as an anesthetic adjuvant in patients undergoing cancer surgery. The present non-double blinded randomized trial was conducted at Hirosaki University Hospital with 60 patients who underwent minimally invasive robotic radical prostatectomy to minimize the immunomodulation due to surgical stress. Patients received total intravenous anesthesia using propofol and remifentanil, with ketamine as an anesthetic adjuvant (the ketamine group) or without ketamine (the control group). The primary outcome was the difference in NKCC between these groups. The secondary outcomes were the differences in neutrophil-lymphocyte ratio (NLR) and levels of interleukin (IL)-6, IL-1ß, IL-10 and tumor necrosis factor-alpha (TNF-α). NKCC and cytokines were measured before anesthesia (baseline) and at 6 and 24 h after baseline measurements were recorded. NLR was determined on the last day before admission and at 48 h post-baseline. NKCC values were similar in each group at 6 h when compared with respective baseline results (baseline control, 36.9±15.6%; 6 h control, 38.3±13.4%; baseline ketamine, 36.1±17.0%; 6 h ketamine, 36.6±16.4%) but significantly decreased at 24 h (control, 26.5±12.2%; ketamine, 24.1±12.7%; P<0.001). There were no significant differences in NKCC between the ketamine and control groups (P=0.64) at any of the assessed time points. NLR, IL-1ß, IL-10 and TNF-α levels were also similar between two groups. In contrast, IL-6 at 24 h was significantly lower in the ketamine group compared with the control group (mean difference, -7.3 pg ml-1; 95% confidence interval, -14.4 to -0.2; P=0.04). Ketamine as an anesthetic adjuvant did not provide direct immunomodulation in patients who underwent cancer surgery.

Successful respiratory management of a Marshall-Smith syndrome patient with a tracheo-innominate artery fistula.

BACKGROUND: Tracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF. CASE PRESENTATION: A 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications. CONCLUSIONS: A cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult.

Negative item memory and associative memory: Influences of working memory capacity, anxiety sensitivity, and looming cognition.

BACKGROUND AND OBJECTIVES: Traumatic or negative stimuli facilitate item memory but impair associated context memory. Vulnerability factors related to the maintenance and onset of posttraumatic stress disorder (PTSD), such as anxiety sensitivity, looming cognitive style, dissociation, and low working memory capacity, have been identified. However, little is known about how these factors influence negative item or associative memory. METHODS: Eighty-five undergraduates completed self-report questionnaires, the operation span with words (OSPAN) task, and an item and associative memory task in which incidental encoding of negative and neutral items and context information (Day 1) was followed by an unexpected retrieval test (Day 2). RESULTS: The results showed greater Hit rates and False Alarms on item memory and lower accuracy on context memory with negative stimuli than with neutral stimuli, replicating previous findings. Low working memory capacity and high dissociation were correlated with low negative item memory. Under low working memory capacity, high levels of anxiety sensitivity and looming cognitive style predicted high dissociation levels and low accuracy for negative item memory. There were no individual differences involving associative memory. LIMITATIONS: A nonclinical sample was used, which limits the generalizability of our results to clinical samples. CONCLUSIONS: Dissociation could be a coping strategy for reducing negative item memory. Anxiety sensitivity and looming cognitive style facilitate dissociative coping; however, working memory capacity buffers against these vulnerabilities.

Spontaneous Activation of Event Details in Episodic Future Simulation.

Episodic future simulation is supported by both the retrieval and recombination of episodic details. It remains unclear, however, how individuals retrieve episodic details from memory to construct possible future scenarios; for this people must use details related to the planned future events appropriately. A potentially relevant cognitive process is the spontaneous activation of intention observed in prospective memory (i.e., the intention superiority effect). Previous studies on prospective memory have shown that the approximation of retrieval opportunities for future intentions activate related information, suggesting that the intention superiority effect is context-sensitive. We hypothesized that the same cognitive process underlies future simulation-that is, details related to future events should spontaneously become activated at the appropriate moment of future simulation to make that simulation plausible. In Experiment 1, participants took part in future experiments and formed intentions to perform particular actions for the next experiments. Subsequently, they imagined events that could occur up until they arrived at the experimental room on the day of the next experiment. During this exercise, they did not imagine engaging in the required experimental task. We measured the conceptual activation of intention-related information via a recognition task using intended action words as targets. The results showed the intention superiority effect-concepts related to participants' future intentions became active when envisioning future events approaching the next experiment. In Experiments 2 and 3, we ensured that the intention superiority effect in future simulation was context-sensitive by adding a control condition that required participants to imagine events other than the approaching future experiments. These results indicated that concepts related to the intended actions were spontaneously activated when imagined future events became both temporally and spatially close to the future simulation. Our finding suggests that spontaneous activation of details approaching the context of a future simulation helps in constructing plausible future scenarios.

Preoperative cerebral and renal oxygen saturation and clinical outcomes in pediatric patients with congenital heart disease.

We examined the predictability of preoperative cerebral and renal rSO2 values for outcomes in pediatric patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). Patients who underwent pediatric cardiac surgery under CPB between September 2015 and September 2017 were enrolled in this study. Patients monitored with both cerebral and renal rSO2 at the beginning of surgery were included. The primary outcome was the prediction of outcomes after pediatric cardiac surgery. Outcome was defined as any of: (1) death within 30 days after surgery, or the need for (2) renal replacement therapy or (3) extracorporeal membrane oxygenation, (4) shorten mechanical ventilator-free day,(5) shorten ICU-free survival day. We included 59 patients: cyanotic n = 31; non-cyanotic n = 28. Among all patients, 15 (25%) had poor outcomes, including three deaths. The cerebral and renal rSO2 values were significantly lower in the cyanotic patients with poor outcomes compared to those without poor outcomes (cerebral: 59 ± 11 vs. 50 ± 5, p = 0.021; renal: 59 ± 15 vs. 51 ± 14, p = 0.015) but only the renal rSO2 value was significantly lower in the non-cyanotic patients (77 ± 10 vs. 61 ± 14, p = 0.011). The cut-off value (51%) of cerebral rSO2 were associated with risk of mechanical ventilator-free day and ICU-free survival day [ORs of 22.8 (95% CI 2.21-235.0, p = 0.0087) and 15.8 (95% CI 1.53-164.0, p = 0.0204), respectively] in the cyanotic patients. The cut-off value (66%) of cerebral rSO2 value was associated with risk of mechanical ventilator-free day [OR of 11.3 (95% CI 1.05-25.3, p = 0.0456)] and the cut-off value (66%) of renal rSO2 value was associated with risk of ICU-free survival day [ORs of 33.0 (95% CI 2.25-484.0, p = 0.0107)] in the noncyanotic patients. The preoperative low rSO2 values were associated with outcomes including 30-day mortality and might be reflective of the severity of cardiopulmonary function. Further studies are needed to confirm our results.

Patent ductus arteriosus closure and somatic regional oxyhemoglobin saturation.

The authors report a case of a 14-day-old infant patient with patent ductus arteriosus (PDA) with pulmonary hypertension. Accidental clipping of the left pulmonary artery (LPA) during intended PDA closure was revealed, and subsequent urgent PDA closure and releasing a clip of the LPA were conducted. During surgeries we measured somatic regional oxyhemoglobin saturation (rSO2) values and change in those might be a key for early diagnosis of accidental clipping of the LPA. These findings suggest that we should understand the risk of accidental closure of the LPA during PDA surgery and somatic rSO2 values will provide information for early diagnosis of critical complication.

An Extension of a Parallel-Distributed Processing Framework of Reading Aloud in Japanese: Human Nonword Reading Accuracy Does Not Require a Sequential Mechanism.

Humans can pronounce a nonword (e.g., rint). Some researchers have interpreted this behavior as requiring a sequential mechanism by which a grapheme-phoneme correspondence rule is applied to each grapheme in turn. However, several parallel-distributed processing (PDP) models in English have simulated human nonword reading accuracy without a sequential mechanism. Interestingly, the Japanese psycholinguistic literature went partly in the same direction, but it has since concluded that a sequential parsing mechanism is required to reproduce human nonword reading accuracy. In this study, by manipulating the list composition (i.e., pure word/nonword list vs. mixed list), we demonstrated that past psycholinguistic studies in Japanese have overestimated human nonword reading accuracy. When the more fairly reevaluated human performance was targeted, a newly implemented Japanese PDP model simulated the target accuracy as well as the error patterns. These findings suggest that PDP models are a more parsimonious way of explaining reading across various languages.

People Like Logical Truth: Testing the Intuitive Detection of Logical Value in Basic Propositions.

Recent studies on logical reasoning have suggested that people are intuitively aware of the logical validity of syllogisms or that they intuitively detect conflict between heuristic responses and logical norms via slight changes in their feelings. According to logical intuition studies, logically valid or heuristic logic no-conflict reasoning is fluently processed and induces positive feelings without conscious awareness. One criticism states that such effects of logicality disappear when confounding factors such as the content of syllogisms are controlled. The present study used abstract propositions and tested whether people intuitively detect logical value. Experiment 1 presented four logical propositions (conjunctive, biconditional, conditional, and material implications) regarding a target case and asked the participants to rate the extent to which they liked the statement. Experiment 2 tested the effects of matching bias, as well as intuitive logic, on the reasoners' feelings by manipulating whether the antecedent or consequent (or both) of the conditional was affirmed or negated. The results showed that both logicality and matching bias affected the reasoners' feelings, and people preferred logically true targets over logically false ones for all forms of propositions. These results suggest that people intuitively detect what is true from what is false during abstract reasoning. Additionally, a Bayesian mixed model meta-analysis of conditionals indicated that people's intuitive interpretation of the conditional "if p then q" fits better with the conditional probability, q given p.

Involvement of the Ventrolateral Prefrontal Cortex in Learning Others' Bad Reputations and Indelible Distrust.

A bad reputation can persistently affect judgments of an individual even when it turns out to be invalid and ought to be disregarded. Such indelible distrust may reflect that the negative evaluation elicited by a bad reputation transfers to a person. Consequently, the person him/herself may come to activate this negative evaluation irrespective of the accuracy of the reputation. If this theoretical model is correct, an evaluation-related brain region will be activated when witnessing a person whose bad reputation one has learned about, regardless of whether the reputation is deemed valid or not. Here, we tested this neural hypothesis with functional magnetic resonance imaging (fMRI). Participants memorized faces paired with either a good or a bad reputation. Next, they viewed the faces alone and inferred whether each person was likely to cooperate, first while retrieving the reputations, and then while trying to disregard them as false. A region of the left ventrolateral prefrontal cortex (vlPFC), which may be involved in negative evaluation, was activated by faces previously paired with bad reputations, irrespective of whether participants attempted to retrieve or disregard these reputations. Furthermore, participants showing greater activity of the left ventrolateral prefrontal region in response to the faces with bad reputations were more likely to infer that these individuals would not cooperate. Thus, once associated with a bad reputation, a person may elicit evaluation-related brain responses on their own, thereby evoking distrust independently of their reputation.

[Development of the Japanese version of the Thought Control Ability Questionnaire and evaluation of its reliability and validity].

Intrusive thoughts and difficulty in controlling thoughts are common, not only for people with psychological disorders, but also for healthy people. Individual differences in thought control ability may underlie such problems. The Thought Control Ability Questionnaire (TCAQ), which consists of 25 items, was developed by Luciano et al. (2005) in order to measure individual differences in the perceived ability to control unwanted intrusive thoughts. The purpose of the present study was to develop the Japanese version of the TCAQ and evaluate its reliability and validity. We translated the English version of the TCAQ into Japanese. We also conducted confirmatory factor analysis with a one factor solution, similar to the previous study. Based on the analysis, we excluded items whose factor loadings were lower than .30, resulting in 22 items for the Japanese version of the TCAQ. The model exhibited acceptable goodness-of-fit. The Japanese version of the TCAQ also demonstrated good reliability as well as evidence of construct validity. Thus, the development of the Japanese version of the TCAQ was successful.

[Remembering past events activates temporal concepts of future].

The cognitive function to project oneself into the specific past or future is labeled mental time travel (MTT). MTT to the past is considered "episodic memory" and the future is termed "episodic future thinking". Remembering the past and imaging the future during MTT both draw on information stored in episodic memory: a process that enables integration of episodic information into a coherent event representation. Recent studies suggested that episodic information in past/future event representations varies with temporal distance from the present to the event. However, it is unclear whether the influence on temporal distance is actually caused by the function of episodic memory retrieval. The present study investigated the relationship between episodic memory and temporal concepts with a lexical decision task. The results indicate that remembering the past activated temporal concepts of the near future more than that of the far future. This finding suggests that the rich information derived from episodic memory modulates the subjective sense of time in episodic future thinking.

Why Verbalization of Non-Verbal Memory Reduces Recognition Accuracy: A Computational Approach to Verbal Overshadowing.

Verbal overshadowing refers to a phenomenon whereby verbalization of non-verbal stimuli (e.g., facial features) during the maintenance phase (after the target information is no longer available from the sensory inputs) impairs subsequent non-verbal recognition accuracy. Two primary mechanisms have been proposed for verbal overshadowing, namely the recoding interference hypothesis, and the transfer-inappropriate processing shift. The former assumes that verbalization renders non-verbal representations less accurate. In contrast, the latter assumes that verbalization shifts processing operations to a verbal mode and increases the chance of failing to return to non-verbal, face-specific processing operations (i.e., intact, yet inaccessible non-verbal representations). To date, certain psychological phenomena have been advocated as inconsistent with the recoding-interference hypothesis. These include a decline in non-verbal memory performance following verbalization of non-target faces, and occasional failures to detect a significant correlation between the accuracy of verbal descriptions and the non-verbal memory performance. Contrary to these arguments against the recoding interference hypothesis, however, the present computational model instantiated core processing principles of the recoding interference hypothesis to simulate face recognition, and nonetheless successfully reproduced these behavioral phenomena, as well as the standard verbal overshadowing. These results demonstrate the plausibility of the recoding interference hypothesis to account for verbal overshadowing, and suggest there is no need to implement separable mechanisms (e.g., operation-specific representations, different processing principles, etc.). In addition, detailed inspections of the internal processing of the model clarified how verbalization rendered internal representations less accurate and how such representations led to reduced recognition accuracy, thereby offering a computationally grounded explanation. Finally, the model also provided an explanation as to why some studies have failed to report verbal overshadowing. Thus, the present study suggests it is not constructive to discuss whether verbal overshadowing exists or not in an all-or-none manner, and instead suggests a better experimental paradigm to further explore this phenomenon.

Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.

PURPOSE: The purpose of this study was to investigate the latency and amplitude of trigeminal somatosensory evoked potentials to clarify how nerve function on the contralateral side is affected after cervical sympathetic block (CSB). METHODS: Subjects comprised 16 volunteers. For CSB, the tip of a needle was contacted with the transverse process of the sixth cervical vertebra on the right side, and lidocaine was injected. Trigeminal somatosensory evoked potentials were recorded bilaterally from C5/C6 scalp positions. Pupil diameters were also measured. Electrical stimulations were applied to the left-side lower lip, and trigeminal somatosensory evoked potentials waveforms derived from both sides of the scalp were recorded. Then, electrical stimulations were applied to the right-side of the lower lip, and recording was again performed. Recordings were performed at 5, 15, and 30 minutes after CSB. RESULTS: On the CSB side, pupil diameter decreased at 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials at contralateral stimulation showed a prolongation of the latency in both P20 and N25 components on bilateral recording sites 5 and 15 minutes after CSB. Trigeminal somatosensory evoked potentials' amplitude at contralateral stimulation was smaller than at ipsilateral stimulation 5 minutes after CSB. CONCLUSIONS: Cervical sympathetic block prolongs the latency and reduces the amplitude of trigeminal somatosensory evoked potentials on the contralateral side.