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Sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose) is a sulfosugar that is the anionic head group of plant, algal, and cyanobacterial sulfolipids: sulfoquinovosyl diacylglycerols. SQ is produced within photosynthetic tissues, forms a major terrestrial reservoir of biosulfur, and is an important species within the biogeochemical sulfur cycle. A major pathway for SQ breakdown is the sulfoglycolytic Embden-Meyerhof-Parnas pathway, which involves cleavage of the 6-carbon chain of the intermediate sulfofructose-1-phosphate (SFP) into dihydroxyacetone and sulfolactaldehyde, catalyzed by class I or II SFP aldolases. While the molecular basis of catalysis is understood for class I SFP aldolases, comparatively little is known about class II SFP aldolases. Here, we report the molecular architecture and biochemical basis of catalysis of two metal-dependent class II SFP aldolases from Hafnia paralvei and Yersinia aldovae. 3D X-ray structures of complexes with substrate SFP and product dihydroxyacetone phosphate reveal a dimer-of-dimers (tetrameric) assembly, the sulfonate-binding pocket, two metal-binding sites, and flexible loops that are implicated in catalysis. Both enzymes were metal-dependent and exhibited high K M values for SFP, consistent with their role in a unidirectional nutrient acquisition pathway. Bioinformatic analysis identified a range of sulfoglycolytic Embden-Meyerhof-Parnas gene clusters containing class I/II SFP aldolases. The class I and II SFP aldolases have mututally exclusive occurrence within Actinobacteria and Firmicutes phyla, respectively, while both classes of enzyme occur within Proteobacteria. This work emphasizes the importance of SQ as a nutrient for diverse bacterial phyla and the different chemical strategies they use to harvest carbon from this sulfosugar., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays there are numerous studies on the occurrence of cognitive dysfunction in late-life depression (LLD). The role of executive dysfunctions in the psychopathology of depression is particularly emphasized and needs further examination. The aim was to assess cognitive functions and their relation to depressive symptoms in elders with LLD, previously depressed, and patients without the history of depressive episodes. The study consisted of 824 older adults who underwent a neuropsychological evaluation (97 currently depressed, 114 previously depressed and 613 patients without the history of depressive episodes). LLD patients performed poorer in ACE-III and AVLT and poorer in TMT-B than those previously depressed and never depressed. The LLD group also performed significantly poorer than the previously depressed on Digit Span Forward. Results of a multiple regression analysis indicated that performance on measures of executive functioning was associated with depression severity in LLD (β =.227, P =.024). The results of this study suggest that executive functions are the most impaired in the elderly with LLD. Furthermore, there is a relationship between executive dysfunction and the severity of depression in LLD. Executive dysfunction appears to be the core neurocognitive deficit in LLD.

Background: Empathy plays the key role in the doctor - patient relationship. The research of empathy determinants plays an important role in formulating practical guidelines for the education of medical students. The aim of this study was to analyse personality characteristics of empathy profiles among students of medicine, with consideration of chief personality factors and their subdimensions according to the FFM model., Methods: During workshops in Clinical Psychological Skills, 153 students (M = 57, F = 96; mean age 23 years) analysed their psychological functioning styles by examining their personality profiles and empathy indicators. Empathic Sensitiveness Scale (ESS) and Personality Inventory (NEO-PI-R) were applied for this purpose. The analyses of empathy indicators were presented by means of cluster analysis. Variance analysis with post hoc Tukey-b test was performed for differences between clusters and to differentiate between personality factors and their components in empathy clusters. This study was approved by the Jagiellonian University Bioethics Committee (approval number: 1072.6120.175.2018 date: 28.06.2018)., Results: The first cluster included students who presented high empathetic concern for others, understood their perspective and needs characterised by medium level of Neuroticism, high levels of other dimensions The second group included students who could understand others very well, yet with lower tendency to react emotionally to suffering, characterised by medium level of Neuroticism, Extraversion, Openness, high Conscientiousness and low Agreeableness. The third cluster included students who react strongly to painful and unpleasant reactions of others, characterised by high Neuroticism and Agreeableness, low Extraversion., Conclusions: Each empathy profile is manifested in relations with patients in a specific way. Medical education in empathy holds great potential to reduce anxiety, stress, and burnout associated with the medical profession. Discussion of individual results with students, gives an opportunity to talk about how their empathy and personality characteristics may influence their everyday medical practice., (© 2022. The Author(s).)

Sulfoquinovose (SQ) is the anionic headgroup of the ubiquitous plant sulfolipid, sulfoquinovosyl diacylglycerol (SQDG). SQDG can undergo delipidation to give sulfoquinovosyl glycerol (SQGro) and further glycoside cleavage to give SQ, which can be metabolized through microbial sulfoglycolytic pathways. Exogenous SQDG metabolites are imported into bacteria through membrane spanning transporter proteins. The recently discovered sulfoglycolytic sulfoquinovose monooxygenase (sulfo-SMO) pathway in Agrobacterium tumefaciens features a periplasmic sulfoquinovosyl glycerol binding protein, SmoF, and an ATP-binding cassette (ABC) transporter. Here, we use X-ray crystallography, differential scanning fluorimetry and isothermal titration calorimetry to study SQ glycoside recognition by SmoF. This work reveals that in addition to SQGro, SmoF can also bind SQ, a simple methyl glycoside and even a short-chain SQDG analogue. Molecular recognition of these substrates is achieved through conserved interactions with the SQ-headgroup together with more plastic interactions with the aglycones. This suggests that the solute binding protein of A. tumefaciens, and related SQ-binding proteins from other sulfoglycolytic pathways, can provide their host organisms direct access to most of the SQ metabolites known to be produced by phototrophs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Catabolism of sulfoquinovose (SQ; 6-deoxy-6-sulfoglucose), the ubiquitous sulfosugar produced by photosynthetic organisms, is an important component of the biogeochemical carbon and sulfur cycles. Here, we describe a pathway for SQ degradation that involves oxidative desulfurization to release sulfite and enable utilization of the entire carbon skeleton of the sugar to support the growth of the plant pathogen Agrobacterium tumefaciens SQ or its glycoside sulfoquinovosyl glycerol are imported into the cell by an ATP-binding cassette transporter system with an associated SQ binding protein. A sulfoquinovosidase hydrolyzes the SQ glycoside and the liberated SQ is acted on by a flavin mononucleotide-dependent sulfoquinovose monooxygenase, in concert with an NADH-dependent flavin reductase, to release sulfite and 6-oxo-glucose. An NAD(P)H-dependent oxidoreductase reduces the 6-oxo-glucose to glucose, enabling entry into primary metabolic pathways. Structural and biochemical studies provide detailed insights into the recognition of key metabolites by proteins in this pathway. Bioinformatic analyses reveal that the sulfoquinovose monooxygenase pathway is distributed across Alpha- and Betaproteobacteria and is especially prevalent within the Rhizobiales order. This strategy for SQ catabolism is distinct from previously described pathways because it enables the complete utilization of all carbons within SQ by a single organism with concomitant production of inorganic sulfite., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

The issues of personality and its relations with the level of empathetic sensibility of medical doctors are broadly discussed in the literature. The aim of this study was an assessment of personality related predictors of empathy indicators in female and male students of medicine with consideration of gender differences. Methods applied were Empathic Sensitiveness Scale (ESS) and Personality Inventory (NEO-PI-R). The study included 153 participants, who were students of the fifth year of medical studies. Students filled in questionnaires during workshops in clinical psychological skills. Participation in the study was voluntary and anonymous. The statistical analysis was performed using Statistica 13 PL and PS IMAGO PRO (SPSS). Linear regression analysis with the interaction component was performed to explore the relationship between personality factors and gender and their interaction with the variable dependent level of empathy. The analysis showed that Extraversion, Openness and Agreeableness are associated with the level of Empathic Concern. Neuroticism, Extraversion, Agreeableness and Conscientiousness are associated with the level of Personal Distress. Extraversion, Openness, Agreeableness and Conscientiousness are associated with the level of Perspective-taking. The regression analysis with the interactive component showed that there is no relationship between gender and the level of empathy, therefore the interactions were insignificant. Empathetic sensibility is related to personality dimensions of the students of medicine. Although there has been no interaction among chief personality dimensions, empathy indicators and gender, detailed analysis of personality dimensions' components has shown differences between men and women., Competing Interests: The authors have declared that no competing interests exist.

The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on Earth and is metabolized by bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolizes SQ to produce dihydroxyacetone phosphate and sulfolactaldehyde and is analogous to the classical Embden-Meyerhof-Parnas glycolysis pathway for the metabolism of glucose-6-phosphate, though the former only provides one C3 fragment to central metabolism, with excretion of the other C3 fragment as dihydroxypropanesulfonate. Here, we report a comprehensive structural and biochemical analysis of the three core steps of sulfoglycolysis catalyzed by SQ isomerase, sulfofructose (SF) kinase, and sulfofructose-1-phosphate (SFP) aldolase. Our data show that despite the superficial similarity of this pathway to glycolysis, the sulfoglycolytic enzymes are specific for SQ metabolites and are not catalytically active on related metabolites from glycolytic pathways. This observation is rationalized by three-dimensional structures of each enzyme, which reveal the presence of conserved sulfonate binding pockets. We show that SQ isomerase acts preferentially on the β-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a derepressor for the transcriptional repressor CsqR that regulates SQ-utilization. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex modulation by the metabolites SQ, SLA, AMP, ADP, ATP, F6P, FBP, PEP, DHAP, and citrate, and we show that SFP aldolase reversibly synthesizes SFP. This body of work provides fresh insights into the mechanism, specificity, and regulation of sulfoglycolysis and has important implications for understanding how this biochemistry interfaces with central metabolism in prokaryotes to process this major repository of biogeochemical sulfur., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Rhizobia are nitrogen-fixing bacteria that engage in symbiotic relationships with plant hosts but can also persist as free-living bacteria in the soil and rhizosphere. Here, we show that free-living Rhizobium leguminosarum SRDI565 can grow on the sulfosugar sulfoquinovose (SQ) or the related glycoside SQ-glycerol using a sulfoglycolytic Entner-Doudoroff (sulfo-ED) pathway, resulting in production of sulfolactate (SL) as the major metabolic end product. Comparative proteomics supports the involvement of a sulfo-ED operon encoding an ABC transporter, sulfo-ED enzymes, and an SL exporter. Consistent with an oligotrophic lifestyle, proteomics data revealed little change in expression of the sulfo-ED proteins during growth on SQ versus mannitol, a result confirmed through biochemical assay of sulfoquinovosidase activity in cell lysates. Metabolomics analysis showed that growth on SQ involves gluconeogenesis to satisfy metabolic requirements for glucose-6-phosphate and fructose-6-phosphate. Metabolomics analysis also revealed the unexpected production of small amounts of sulfofructose and 2,3-dihydroxypropanesulfonate, which are proposed to arise from promiscuous activities of the glycolytic enzyme phosphoglucose isomerase and a nonspecific aldehyde reductase, respectively. The discovery of a rhizobium isolate with the ability to degrade SQ builds our knowledge of how these important symbiotic bacteria persist within soil. IMPORTANCE Sulfonate sulfur is a major form of organic sulfur in soils but requires biomineralization before it can be utilized by plants. Very little is known about the biochemical processes used to mobilize sulfonate sulfur. We show that a rhizobial isolate from soil, Rhizobium leguminosarum SRDI565, possesses the ability to degrade the abundant phototroph-derived carbohydrate sulfonate SQ through a sulfoglycolytic Entner-Doudoroff pathway. Proteomics and metabolomics demonstrated the utilization of this pathway during growth on SQ and provided evidence for gluconeogenesis. Unexpectedly, off-cycle sulfoglycolytic species were also detected, pointing to the complexity of metabolic processes within cells under conditions of sulfoglycolysis. Thus, rhizobial metabolism of the abundant sulfosugar SQ may contribute to persistence of the bacteria in the soil and to mobilization of sulfur in the pedosphere., (Copyright © 2020 American Society for Microbiology.)

Sulfoglycolysis is a metabolic pathway dedicated to the catabolism of the sulfosugar sulfoquinovose (SQ) into smaller organosulfur fragments. An estimated 10 billion tonnes of SQ fluxes through sulfoglycolysis pathways each year, making it a significant aspect of the biogeochemical sulfur cycle. Delineating the molecular details of sulfoglycolysis requires authentic samples of the various metabolites in these pathways. To this end, we have established chemical and chemoenzymatic methods for the synthesis of the key organosulfur metabolites sulfoquinovosylglycerol, SQ (also in 13 C 6 -labeled form), sulfofructose, sulfofructose-1-phosphate, sulfolactaldehyde, and 2,3-dihydroxypropanesulfonate, as well as an improved route to the chromogenic sulfoquinovosidase substrate 4-nitrophenyl α-sulfoquinovoside.

Objective: Introduction: Cognitive limitations are a serious health and social problem, which concerns elderly people. Effective prevention and treatment of cognitive dysfunction is one of the challenges of modern medicine. There is not enough consistent data in the literature to indicate to indicate the relationship between various clinical and demographic factors with cognitive functioning in different age ranges. The aim: To analyze clinical and demographic predictors of mild cognitive impairment by age group., Patients and Methods: Material and methods: The analysis included 817 participants (669 with normal cognitive function and 148 people with MCI). The evaluation of the level of depressive symptoms was measured by the Short Form Geriatric Depression Scale. All participants were screened for cognitive functioning using the Mini-Mental State Examination and Addenbrooke's Cognitive Examination-III. Different cognitive domains were evaluated with different neuropsychological tools: the Rey Auditory Verbal Learning test, Clock Drawing test, Verbal Fluency test, Digit Span Test and Trail Making test., Results: Results: It has been shown that independently associated with MCI ware age (OR = 1.09, 95% CI: 1.05-1.13) and level of education (OR = 0.75, 95% CI: 0.69-0.81). Depending on the age, it turned out that in the younger MCI group, age, education and depression were significant, and the age and level of education were significant in the older MCI group., Conclusion: Conclusions: The identification of cognitive dysfunctions is an important element of the diagnostic and therapeutic process.

Developing the empathic attitude is one of the tasks of medical education as it affects the quality of therapeutic contact in the relationship between the doctor and the participant, conditioning the treatment process. According to Davis's concept, empathy is defined as an affective-cognitive reaction in the context of the other person's experience., Aim: Analysis of profiles of empathic sensitivity in students of medicine. Group: Male and female students of the fifth year of medicine who agreed to participate in an anonymous study (n = 153; M = 57, F = 96; mean age: 23 years). Tools: The Empathetic Sensitivity Scale (EES), which is the Polish tool for Davis's Interpersonal Reactivity Index (IRI) was used. The ESS includes three sub-scales: Empathic Care (EC), Personal Distress (PD) and Adopting Perspective (AP)., Results: The raw results were converted into sten scores and for sten scores for all three dimensions of empathetic sensitivity no differences were found between male and female students. Three clusters (1: n = 33%, 2: n = 39%, 3: n = 28%), which differ in terms of each distinguished indicator, were identified., Conclusions: The first cluster characterizes empathetic people, both in the affective and cognitive spheres, and those dealing well with unpleasant emotions in situations difficult to others. The second cluster characterizes participants with the ability to recognize the needs of others and to take into account their perspectives; the third cluster includes participants with a tendency to focus on own experiences emerging in response to other people's suffering but with the ability to understand a situation and show empathic concern for the other person. The most favourable profile - for a future doctor as well as for his participants - is the first cluster because the doctor, with his empathic sensitivity directed towardsthe other man, can deal with his own unpleasant emotions.

Unlabelled: AIM : The relationships between obesity and bipolar spectrum disorders (BSD) are unclear. Thus, the aim of our study were to approximate the prevalence of soft bipolar features in patients seeking treatment for obesity., Methods: We performed a nested case-control study (cases: 90 patients with the mean BMI=38.1±7.0 [range: 30.1-62.5]; controls: 70 healthy volunteers with the mean BMI=21.6±2.1 [range: 18.5-24.9]). The participants were screened for the BSD symptoms with the Mood Disorder Questionnaire., Results: Patients with obesity were significantly more likely to score ≥7 pts. on the MDQ 25.6% vs. 8.6%; p=0.01). In comparison to non-obese individuals, the obese patients scored significantly higher in MDQ section I and on the MDQ items referring to the 'irritability-racing thoughts' dimension of hypomania. The multiple logistic regression analysis revealed that obesity had been significantly related to the odds of obtaining ≥7 pts. on the MDQ section 1 (odds ratio [OR] = 2.07; 95% confidence interval [CI]: 1.17-3.63), and marginally significantly related to experiencing periods of 'ups' and 'downs'(OR = 1.67; 95% CI: 1.00-2.81)., Conclusions: Our study adds to previous suggestions that obesity may be significantly related to the BSD. However, the clinical implications of this finding need to be determined in further studies, performed in accordance with the paradigm of evidence based medicine (EBM).

Aim: The subject of the research presented in this paper was to analyze the relationships between bipolar disorder (BD) and the profile of moral reasoning according to the concept of James Rest., Material and Methods: 86 persons took part in the research, including 43 bipolar patients and 43 healthy individuals. To measure the severity of depression and mania symptoms the following scales were used: Hamilton Rating Scale for Depression (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS) and Young Rating Scale for Mania (YMRS). Profile of moral reasoning was defined on the basis of the results obtained in the Defining Issue Test (DIT) by James Rest., Results: Statistical analysis showed that there is a relationship between bipolar disorder (and its phases) and the profile of moral reasoning: bipolar patients significantly less often than healthy individuals chose answers indicating the postconventional thinking (p = 0.000) - and more often - answers indicating stage 3 and those belonging to the anti-institutional thinking index (p = 0.000). There was also a relationship shown between the development of moral reasoning and the phase of bipolar disorder: patients in mania less often than persons in euthymia chose answers indicating the final stage of moral thinking (p = 0.050). There were no significant differences between the results of patients with a depressive episode and the results of patients in mania and between the results of patients with a depressive episode and the results of patients in euthymia., Conclusions: The results suggest that the psychological state of the individual may have an impact on the process of moral reasoning - bipolar disorder may to some extent influence the way of thinking about moral dilemmas. The collected data also seem to emphasize the specificity of the manic phase which is especially worth exploration when conducting further studies.

The differentiation of precursor cells into neurons has been shown to be influenced by both the Notch signaling pathway and growth factor stimulation. In this study, the regulation of neuronal differentiation by these mechanisms was examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By downregulating Notch1 expression and by the addition of a Delta1 fusion protein (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron differentiation in the NEP cells, in vitro. The expression of two of the Notch receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells was found to be influenced by a number of different growth factors, indicating a potential interaction between growth factors and Notch signaling. Interestingly, none of the growth factors examined promoted neuron differentiation; however, the fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1 and FGF2 upregulated the expression of Notch and decreased expression of Delta1 in the NEP cells. In addition, the inhibitory response of the cells to the FGFs could be overcome by downregulating Notch1 expression and by disrupting Notch cleavage and signaling by the ablation of the Presenilin1 gene. These results indicate that FGF1 and FGF2 act via the Notch pathway, either directly or indirectly, to inhibit differentiation. Thus, signaling through the Notch receptor may be a common regulator of neuronal differentiation within the developing forebrain.

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB., (Copyright 2000 Wiley-Liss, Inc.)