Patient-reported cognitive impairments and objective neuropsychological deficits in young sarcoma patients undergoing chemotherapy and its comparison to healthy controls: A tertiary health care study from India.

The study aims to investigate the patient-reported cognitive deficits and objective neuropsychological functions in younger adult (YA) sarcoma patients (16-40 years of age). Ninety patients and 30 age-matched healthy controls from a single tertiary healthcare hospital, were recruited into four groups: Pre-chemotherapy (Pre Cx), During chemotherapy (During Cx), Post-chemotherapy (Post Cx) and Controls. Neurocognitive functions were assessed subjectively using FACT-Cog v3 questionnaire; objectively using ACE-III and neuropsychological tests (NPT). FACT-Cog scores of During Cx (P = .041) and Post Cx (P = .008) groups were significantly lower than Pre Cx group. ACE-III scores of During Cx (P = .048) and Post Cx (P = .043) groups were lower as compared to Pre Cx group. In addition, reaction times and accuracies of the NPT (Flanker's, Sternberg's and Emotional Stroop tests) were worse (P < .05) in During Cx and Post Cx groups as compared to either Pre Cx or control groups. In the Post Cx group, the dose of chemotherapy showed significant negative correlation with the Sternberg reaction time (P = .040) as well as the scores of language (P = .047), and attention (P = .044) domains of ACE-III. Observations demonstrate that cancer/chemotherapy-related neurocognitive deficits fail to improve even after cessation of treatment, and high dosage of chemotherapy used, could be an underlying factor. This emphasizes the need for developing 'model of care' in these patients for monitoring the side effects, and possible titration in the therapeutic regimen for sarcoma in YA.

Postoperative complications after surgery for lumbar spinal stenosis, assessment using two different data sources.

PURPOSE: Lumbar spinal stenosis (LSS) is a prevalent disorder, and surgery for LSS is a common procedure. Postoperative complications occur after any surgery and impose costs for society and costs and additional morbidity for patients. Since complications are relatively rare, medical registries of large populations may provide valuable knowledge. However, recording of complications in registries can be incomplete. To better estimate the true prevalence of complications after LSS surgery, we reviewed two different sources of data and recorded complications for a sample of Norwegian LSS patients. METHODS: 474 patients treated surgically for LSS during 2015 and 2016 at four hospitals reported to a national spine registry (NORspine). Postoperative complications were recorded by patients in NORspine, and we cross-referenced complications documented in NORspine with the patients´ electronic patient records (EPR) to re-test the complication rates. We performed descriptive statistics of complication rates using the two different data sources above, and analyzed the association between postoperative complications and clinical outcome with logistic regression. RESULTS: The mean (95%CI) patient age was 66.3 (65.3-67.2) years, and 254 (53.6%) were females. All patients were treated with decompression, and 51 (10.7%) received an additional fusion during the index surgery. Combining the two data sources, we found a total rate for postoperative complications of 22.4%, the NORspine registry reported a complication rate of 15.6%, and the EPR review resulted in a complication rate of 16.0%. However, the types of complications were inconsistent across the two data sources. According to NORspine, the frequency of reoperation within 90 days was 0.9% and according to EPR 3.4%. The rates of wound infection were for NORspine 3.1% and EPR review 2.1%. There was no association between postoperative complication and patient reported outcome. CONCLUSION: Postoperative complications occurred in 22% of LSS patients. The frequency of different postoperative complications differed between the two data sources.

Pten associates with important gene regulatory network to fine-tune Müller glia-mediated zebrafish retina regeneration.

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. The induction of MGPC through Müller glia-reprograming involves several cellular, genetic and biochemical events soon after a retinal injury. Despite the knowledge on the importance of Phosphatase and tensin homolog (Pten), which is a dual-specificity phosphatase and tumor suppressor in the maintaining of cellular homeostasis, its importance during retina regeneration remains unknown. Here, we explored the importance of Pten during zebrafish retina regeneration. The Pten gets downregulated upon retinal injury and is absent from the MGPCs, which is essential to trigger Akt-mediated cellular proliferation essential for retina regeneration. We found that the downregulation of Pten in the post-injury retina accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that expression of Pten is fine-tuned through Mycb/histone deacetylase1 and Tgf-ß signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.

Characteristics and outcomes of patients who did not respond to a national spine surgery registry.

BACKGROUND: Loss to follow-up may bias outcome assessments in medical registries. This cohort study aimed to analyze and compare patients who failed to respond with those that responded to the Norwegian Registry for Spine Surgery (NORspine). METHODS: We analyzed a cohort of 474 consecutive patients operated for lumbar spinal stenosis at four public hospitals in Norway during a two-year period. These patients reported sociodemographic data, preoperative symptoms, and Oswestry Disability Index (ODI), numerical rating scales (NRS) for back and leg pain to NORspine at baseline and 12 months postoperatively. We contacted all patients who did not respond to NORspine after 12 months. Those who responded were termed responsive non-respondents and compared to 12 months respondents. RESULTS: One hundred forty (30%) did not respond to NORspine 12 months after surgery and 123 were available for additional follow-up. Sixty-four of the 123 non-respondents (52%) responded to a cross-sectional survey done at a median of 50 (36-64) months after surgery. At baseline, non-respondents were younger 63 (SD 11.7) vs. 68 (SD 9.9) years (mean difference (95% CI) 4.7 years (2.6 to 6.7); p = < 0.001) and more frequently smokers 41 (30%) vs. 70 (21%) RR (95%CI) = 1.40 (1.01 to 1.95); p = 0.044. There were no other relevant differences in other sociodemographic variables or preoperative symptoms. We found no differences in the effect of surgery on non-respondents vs. respondents (ODI (SD) = 28.2 (19.9) vs. 25.2 (18.9), MD (95%CI) = 3.0 ( -2.1 to 8.1); p = 0.250). CONCLUSION: We found that 30% of patients did not respond to NORspine at 12 months after spine surgery. Non-respondents were somewhat younger and smoked more frequently than respondents; however, there were no differences in patient-reported outcome measures. Our findings suggest that attrition bias in NORspine was random and due to non-modifiable factors.

Planning and implementation of participant-centric group activity on research methodology: perceptions of postgraduate medical students in physiology.

Knowledge about the key steps in "research methodology" is necessary for all postgraduate students who are enrolled in the medical profession. The objective of the present study was to plan, design, and implement a participant-centric postgraduate skill development activity to inculcate the key principles and components of research methodology. It included 3 goal-oriented component group exercises, namely, 1) framing a research question, 2) critiquing a research article, and 3) writing a research protocol. Out of 25 eligible postgraduate students of our department, 20 participated in all three component group exercises, and they were included in the study. Feedback was obtained from them on a five-point Likert scale after the group exercises. In addition, students were also asked to provide open-ended comments for further improvement of the session. Data from participants' feedback suggested that the majority of the participants expressed satisfaction regarding the plan, conduct, and learning experience of the postgraduate activity. Therefore, participant-centric group activity could be an innovative approach in postgraduate medical education to inculcate the basics of research methodology. It can provide additional emphasis on the components of self-directed learning through individual exercises and unsupervised group dynamics. Supervised group dynamics can inculcate skills in critical thinking, acceptance, communication skills, and teamwork.NEW & NOTEWORTHY Postgraduate medical education is underpinned by supervised and unsupervised learning processes. The current study incorporates an innovative approach to inculcate the basic skills of "research methodology" through three goal-oriented participant-centric group exercises, namely, 1) framing a research question, 2) critiquing a research article, and 3) writing a research protocol. The activities encompass components of self-directed learning through unsupervised group dynamics. They focus on critical thinking, acceptance, communication skills, and teamwork during supervised group dynamics.

Water quality of springs and lakes in the Kumaon Lesser Himalayan Region of Uttarakhand, India.

The scarcity of drinking water has become a bitter reality in many countries. The gap between demand and supply of water has been increasing exponentially year by year. Deforestation, vigorous use of groundwater for agricultural practices, and pollution of our present water resources such as rivers, lakes, and wells are triggering the freshwater scarcity problem. Ninety percent of people in Uttarakhand depend on springs for their daily life activities. In such a case, the quality and quantity of spring water should be a prime topic to be focussed on. In the Kumaon region of Uttarakhand, spring water quality is good but there is an issue with its availability, especially in summer. This review paper details the studies that have been conducted on nutrient status, hardness, heavy metals, and the presence of microbiological diversity in spring water. It also uncovers information on some critical springs, geological settings of their aquifers, and the steps that have been adopted to rejuvenate the spring. Some other measures have been carried out by the government and local communities for springs' revival and their improvement in discharge rate, including the construction of percolation pits, contour trenches, check dams, and improvement of water resources. It has been observed among the analyzed sample that the Kumaon region is dominated by arsenic, cadmium, chromium, and lead, whereas aluminum, barium, cobalt, and manganese are more in the Garhwal region. Apart from springs, this review paper also reveals the physicochemical characteristics of the spring-fed rivers and lakes of the Kumaon region.

Accuracy and agreement of national spine register data for 474 patients compared to corresponding electronic patient records.

PURPOSE: Data quality is essential for all types of research, including health registers. However, data quality is rarely reported. We aimed to assess the accuracy of data in a national spine register (NORspine) and its agreement with corresponding data in electronic patient records (EPR). METHODS: We compared data in NORspine registry against data in (EPR) for 474 patients operated for spinal stenosis in 2015 and 2016 at four public hospitals, using EPR as the gold standard. We assessed accuracy using the proportion correctly classified (PCC) and sensitivity. Agreement was quantified using Kappa statistics or interaclass correlation coefficient (ICC). RESULTS: The mean age (SD) was 66 (11) years, and 54% were females. Compared to EPR, surgeon-reported perioperative complications displayed weak agreement (kappa (95% CI) = 0.51 (0.33-0.69)), PCC of 96%, and a sensitivity (95% CI) of 40% (23-58%). ASA classification had a moderate agreement (kappa (95%CI) = 0.73 (0.66-0.80)). Comorbidities were underreported in NORspine. Perioperative details had strong to excellent agreements (kappa (95% CI) ranging from 0.76 ( 0.68-0.84) to 0.98 (0.95-1.00)), PCCs between 93% and 99% and sensitivities (95% CI) between 92% (0.84-1.00%) and 99% (0.98-1.00%). Patient-reported variables (height, weight, smoking) had excellent agreements (kappa (95% CI) between 0.93 (0.89-0.97) and 0.99 (0.98-0.99)). CONCLUSION: Compared to electronic patient records, NORspine displayed weak agreement for perioperative complications, moderate agreement for ASA classification, strong agreement for perioperative details, and excellent agreement for height, weight, and smoking. NORspine underreported perioperative complications and comorbidities when compared to EPRs. Patient-recorded data were more accurate and should be preferred when available.

Frontal activation as a key for deciphering context congruity and valence during visual perception: An electrical neuroimaging study.

The object-context associations and the valence are two important stimulus attributes that influence visual perception. The current study investigates the neural sources associated with schema congruent and incongruent object-context associations within positive, negative, and neutral valence during an intermittent binocular rivalry task with simultaneous high-density EEG recording. Cortical sourceswere calculated using the sLORETA algorithm in 150 ms after stimulus onset (Stim + 150) and 400 ms before response (Resp-400) time windows. No significant difference in source activity was found between congruent and incongruent associations in any of the valence categories in the Stim + 150 ms window indicating that immediately after stimulus presentation the basic visual processing remains the same for both. In the Resp-400 ms window, different frontal regions showed higher activity for incongruent associations with different valence such as the superior frontal gyrus showed significantly higher activations for negative while the middle and medial frontal gyrus showed higher activations for neutral and finally, the inferior frontal gyrus showed higher activations for positive valence. Besides replicating the previous knowledge of frontal activations in response to context congruity, the current study provides further evidence for the sensitivity of the frontal lobe to the valence associated with the incongruent stimuli.

Electroencephalography-based cortical sources of working memory in the subjects with opioid addiction: A pilot study.

Background & objectives: Working memory impairments in the subjects of opioid addiction may stem from an aberrant cortical activity in the executive areas, and may help in early identification of individuals with addictive tendencies and may also be used as a neurofeedback mechanism in adjunct to the existing therapeutics. Methods: Electrical neuroimaging via 128-channel electroencephalography (EEG) recording was done in 15 male subjects with opioid addiction (29.45±5.6 yr) during the performance of Sternberg Working Memory Task. EEG data were acquired and analyzed for cortical sources during task as compared to resting (baseline) condition. Results: Working memory deficits were manifested as decrease in accuracy percentage in the subjects with opioid addiction, while no significant difference was seen in reaction time, on comparison with laboratory-acquired matched controls. Standardized low-resolution brain electromagnetic tomography (sLORETA)-based EEG source analysis revealed higher cortical activity in the anterior cingulate cortex, inferior, middle and superior temporal gyri, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule and precuneus, whereas significant lower activity was seen in superior and middle frontal gyri, parietal lobule, cingulate cortex and pre- and postcentral gyri when the task was compared to baseline in the subjects with opioid addiction. Further, a negative correlation was seen between the accuracy of task performance and activation ratio for the significant gyri in the subjects with opioid addiction. Interpretation & conclusions: EEG cortical sources revealed the failure of deactivation of default-mode network (DMN) during the task amongst the subjects with opioid addiction. In addition, there was a decrease in the executive function areas in the subjects with opioid addiction. This lack of sufficiently active executive network and persistence of DMN during the task (as compared to baseline) may potentially form the basis of functional impairments in the subjects with opioid addiction.

Student perceptions on synchronous virtual versus face-to-face teaching for leader-centered and participant-centered postgraduate activities during COVID-19.

Consequent to the unprecedented COVID-19 pandemic, pedagogic changes were introduced in postgraduate courses in Physiology, where face-to-face teaching was replaced with synchronous virtual mode for leader-centered (seminar, symposium) and participant-centered (journal club, group discussion) academic activities. We hypothesized that the effectiveness of virtual and face-to-face modes as perceived by postgraduate students in terms of facilitating their overall learning may differ across the spectrum of leader-centered and participant-centered activities. To assess the same, we designed and administered a comprehensive, structured, and validated feedback questionnaire. Postgraduate students (n = 29) rated virtual sessions significantly more convenient, but less attentive and comprehensible, and reported better audiovisual experience during face-to-face sessions. Students rated flexibility to attend, self-paced learning, ability to revise, lookup for information in real time, and accessibility to distant expertise as important features of virtual sessions and instant feedback, eye-to-eye contact, and ability to interact in the group for face-to-face sessions. Virtual and face-to-face sessions were perceived as equally effective in facilitating their overall learning for the conduct of leader-centered seminars and symposia. However, face-to-face sessions were considered more effective for the conduct of participant-centered group discussions and journal clubs. During the pandemic, students perceive the synchronous virtual mode as an equally effective alternative for the conduct of leader-centered academic activities, but face-to-face teaching is still preferred for the conduct of participant-centered academic activities.

Adaptive strategies to conduct participant-centric structured virtual group discussions for postgraduate students in the wake of the COVID-19 pandemic.

In the wake of COVID-19, the postgraduate activities in physiology were shifted from live (face-to-face teaching) to virtual mode. This transition posed a challenge to postgraduate students and faculty moderators, especially for participant-centric group discussion, wherein face-to-face interaction contributes significantly to active learner engagement. To bridge the gap between live group discussion (GD) and virtual GD in the conventional format (VGD), we implemented an innovative yet feasible multistep approach of conducting structured virtual group discussion (sVGD). It involved priming of students during the preparatory phase and incorporation of the Tuckman model of group dynamics, which consists of sequential substages of forming, storming, norming, and performing into the virtual format. Unsupervised synchronous and asynchronous, as well as supervised synchronous interactions within and in between the minigroups in a structured way, led to active engagement of students with one another and the moderator, despite the constraints imposed by the virtual format. After establishing the feasibility of the approach during the first GD (sVGD-1), sVGD-2 was conducted, further refining the approach, and feedback was obtained from the postgraduate students. Pre-GD feedback revealed that the live session was preferred over virtual for the conduct of GD, whereas both live GD and sVGD were perceived to be more effective than VGD in the post-GD feedback. Such pedagogical innovations may also help to address the challenges posed in traditional teaching across the undergraduate and postgraduate courses in medical education and beyond during such unforeseeable circumstances.

Comparison of two formats of journal club for postgraduate students at two centers in developing critical appraisal skills.

Journal club (JC) is an integral part of postgraduate medical education. Although several innovations have been attempted to improve its effectiveness, the influence of the number of sessions remains unexplored. The current study investigated the effect of the number of sessions (one vs. four) of conduction of journal club on critical appraisal skills of postgraduate students at two institutions. A quasi-experimental study was conducted comparing the effectiveness of JC in a one- versus four-session JC format using two objective tests: Critical Appraisal Skills Test (CAST) and Population, Intervention, Comparison, Outcome (PICO) score. The degree of changes (pre-JC vs. post-JC session) after each format exposure, association of prescores to postscores, and correlation between the CAST and PICO scores were discerned. CAST score was higher in the four-session format (P = 0.03), whereas PICO score increased in the single-session format of JC (P = 0.03). Also, the change in CAST score was higher in the four-session versus single-session JC format (P = 0.04). We conclude that a four-session format of JC is more effective in augmenting critical appraisal skills of postgraduate students, whereas a single session is sufficient for improving factual knowledge.

Does valence influence perceptual bias towards incongruence during binocular rivalry?

The efficient processing of complex visual environments is essential for effective functioning. In the natural environment, processing the context is as important as the processing of the target object since no object can be found in isolation. Congruent object-context associations in a visual scene facilitate object recognition, whereas incongruent associations decrease performance accuracy. Although there is a performance reduction, incongruent scenes are reported to have a perceptual bias due to the reallocation of the attentional resources towards the associated semantic conflict. Another key attribute that prepares the visual system to identify the important aspects of the environment is valence, and any visual scene can be classified into one of the three valence categories. Hence, the current study was designed to investigate how valence influences the perceptual bias towards incongruent object-context associations. An intermittent binocular rivalry task was used to measure the perceptual bias across valence categories. The results revealed a significant predominance of incongruent pictures when the associated valence was negative and neutral and remained unbiased for positive valence. We propose a valence-congruency interaction in which perceptual bias towards incongruence is greatly influenced by valence.

Admission Serum Chloride Levels as Predictor of Stay Duration in Acute Decompensated Heart Failure.

OBJECTIVE: Recent studies have shown that lower serum chloride is associated with diuretic resistance and increased mortality in heart failure. Impact of lower admission chloride on duration of stay in acute decompensated heart failure (ADHF) has not been studied previously. METHODS: In this retrospective analysis, we studied the effect of admission serum chloride on the duration of hospital stay in patients admitted with ADHF. A total of 167 patients were studied. Serum chloride levels were divided into tertiles - <96 meq/L (tertile 1), 96-101 meq/L (tertile 2), and >101 meq/L (tertile 3) based on the distribution of serum chloride levels in our patients. RESULTS: The median lengths of hospital stay in tertiles 1, 2, and 3 were 8(Interquartile range :6 -11), 7 (Interquartile range :5 -10.50), and 6 days(Interquartile range :4.25 - 8), respectively (p = 0.011). Admission serum chloride levels were inversely associated with duration of stay (R2 linear = 0.074, p = 0.001). On multiple linear regression analysis, serum chloride remained independent predictor of increased hospital stay (p=0.003) while association with serum sodium was not significant (p=0.07). 1 unit increase in chloride level was associated with 1.3% (p=0.003) decrease in hospital stay (95% CI: 2.2% to 0.5%). CONCLUSION: This retrospective analysis suggests that admission serum chloride levels are independently and inversely associated with increased duration of stay. This is independent of admission sodium levels. Thus serum chloride, rather than sodium, is an important poor prognostic marker in heart failure patients.

Wnt proteins synergize to activate ß-catenin signaling.

Wnt ligands are involved in diverse signaling pathways that are active during development, maintenance of tissue homeostasis and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. Here, we studied the effect of co-expression of Wnts on the ß-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate ß-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate ß-catenin signaling in multiple cell types. WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK. Unexpectedly, this synergistic signaling occurs downstream of ß-catenin stabilization, and is correlated with increased lysine acetylation of ß-catenin. Wnt synergy provides a general mechanism to confer increased combinatorial control over this important regulatory pathway.

Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements.

Rett syndrome is rarely suspected in males because of the X-linked dominant inheritance. In the literature, only six male patients have been reported with methyl-CpG-binding protein 2 (MECP2) mosaicism. Next-generation sequencing (NGS) methods have enabled better detection of somatic mosaicism compared to conventional Sanger sequencing; however, mosaics can still be difficult to detect. We present clinical and molecular findings in two males mosaic for a pathogenic MECP2 variant. Both have been reexamined using deep sequencing of DNA isolated from four different cell tissues (blood, muscle, fibroblasts and oral mucosa). Deep sequencing of the different tissues revealed that the variants were present in all tissues. In one patient, the molecular diagnosis could only be established by reexamination after a normal whole exome sequencing, and the other case is an example of reverse genetic diagnostics. Rett syndrome should be considered in males with neurodevelopmental delay and stereotypical hand movements. Subsequent to clinical diagnosis males should be investigated with NGS-based technologies of MECP2 with high read depth and a low threshold for variant calls. If the initial analysis on full blood derived DNA fails to confirm the suspicion, we recommend repeating the analysis on another tissue, preferentially fibroblasts to increase the diagnostic yield.

Expression and characterization of Flavikunin: A Kunitz-type serine protease inhibitor identified in the venom gland cDNA library of Bungarus flaviceps.

Trancriptomic analysis of the venom gland cDNA library of Bungarus flaviceps revealed Kunitz-type serine protease inhibitor as one of the major venom protein families with three groups A, B, C. One of the group B isoforms named Flavikunin, which lacked an extra cysteine residue involved in disulfide bond formation in ß-bungarotoxin, was synthesized, cloned, and overexpressed in Escherichia coli. To decipher the structure-function relationship, the P1 residue of Flavikunin, histidine, was mutated to alanine and arginine. Purified wild-type and mutant Flavikunins were screened against serine proteases-thrombin, factor Xa, trypsin, chymotrypsin, plasmin, and elastase. The wild-type and mutant Flavikunin (H∆R) inhibited plasmin with an IC 50 of 0.48 and 0.35 µM, respectively. The in-silico study showed that P1 residue of wild-type and mutant (H∆R) Flavikunin interacted with S1' and S1 site of plasmin, respectively. Thus, histidine at the P1 position was found to be involved in plasmin inhibition with mild anticoagulant activity.

Special AT-rich Sequence-binding Protein 1 (SATB1) Functions as an Accessory Factor in Base Excision Repair.

Base excision repair is initiated by DNA glycosylases that recognize specific altered bases. DNA glycosylases for oxidized bases carry both a glycosylase activity that removes the faulty base and an apyrimidinic/apurinic lyase activity that introduces a single-strand DNA incision. In particular, the CUT domains within the CUX1 and CUX2 proteins were recently shown to interact with the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic activities. SATB1, which contains two CUT domains, was originally characterized as a T cell-specific genome organizer whose aberrant overexpression in breast cancer can promote tumor progression. Here we investigated the involvement of SATB1 in DNA repair. SATB1 knockdown caused a delay in DNA repair following exposure to H2O2, an increase in OGG1-sensitive oxidized bases within genomic DNA, and a decrease in 8-oxoG cleavage activity in cell extracts. In parallel, we observed an increase in phospho-CHK1 and γ-H2AX levels and a decrease in DNA synthesis. Conversely, ectopic expression of SATB1 accelerated DNA repair and reduced the levels of oxidized bases in genomic DNA. Moreover, an enhanced GFP-SATB1 fusion protein was rapidly recruited to laser microirradiation-induced DNA damage. Using purified proteins, we showed that SATB1 interacts directly with OGG1, increases its binding to 8-oxoG-containing DNA, promotes Schiff base formation, and stimulates its glycosylase and apyrimidinic/apurinic lyase enzymatic activities. Structure/function analysis demonstrated that CUT domains, but not the homeodomain, are responsible for the stimulation of OGG1. Together, these results identify another CUT domain protein that functions both as a transcription factor and an accessory factor in base excision repair.

Attentional processes, not implicit mentalizing, mediate performance in a perspective-taking task: Evidence from stimulation of the temporoparietal junction.

Mentalizing is a fundamental process underpinning human social interaction. Claims of the existence of 'implicit mentalizing' represent a fundamental shift in our understanding of this important skill, suggesting that preverbal infants and even animals may be capable of mentalizing. One of the most influential tasks supporting such claims in adults is the dot perspective-taking task, but demonstrations of similar performance on this task for mentalistic and non-mentalistic stimuli have led to the suggestion that this task in fact measures domain-general processes, rather than implicit mentalizing. A mentalizing explanation was supported by fMRI data claiming to show greater activation of brain areas involved in mentalizing, including right temporoparietal junction (rTPJ), when participants made self-perspective judgements in a mentalistic, but not in a non-mentalistic condition, an interpretation subsequently challenged. Here we provide the first causal test of the mentalizing claim using disruptive transcranial magnetic stimulation of rTPJ during self-perspective judgements. We found no evidence for a distinction between mentalistic and non-mentalistic stimuli: stimulation of rTPJ impaired performance on all self-perspective trials, regardless of the mentalistic/non-mentalistic nature of the stimulus. Our data support a domain-general attentional interpretation of performance on the dot perspective-taking task, a role which is subserved by the rTPJ.