Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI

<p>Abstract</p> <p>Background</p> <p>The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of <it>AGRP </it>gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).</p> <p>Methods</p> <p>We determined the complete sequence of the <it>AGRP </it>gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m²). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database.</p> <p>Results</p> <p>The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m²(mean, SE) as compared to 30.97 ± 1.03 kg/m²for the CT genotype. No association was found between rs5030980 and BMI.</p> <p>Conclusion</p> <p>This study presents an association of rare allele of <it>AGRP </it>polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.</p

Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle

Abstract Background The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. In addition, circulating miRNA biomarkers offer significant potential towards improving the productivity of livestock species, however, such potential has been hampered by the absence of information on the nature and source of circulating miRNA populations in these species. In addition, many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and thus to actually have limited biomarker utility. In this study, we comprehensively analysed miRNA profiles in plasma and cell fractions of blood from cattle with the aim to identify tissue-derived miRNAs which may be useful as biomarkers of tissue function in this important food animal species. Results Using small RNA sequencing, we identified 92 miRNAs with significantly higher expression in plasma compared to paired blood cell samples (n = 4 cows). Differences in miRNA levels between plasma and cell fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows). Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR-133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for other species. Profiling of additional miRNAs across different tissues identified the human homologue, miR-802, as highly enriched specifically in liver. Conclusions These results provide novel information on the source of bovine circulating miRNAs and could significantly facilitate the identification of production-relevant tissue biomarkers in livestock. In particular, miR-802, a circulating miRNA not previously identified in cattle, can reportedly regulate insulin sensitivity and lipid metabolism, and thus could potentially provide a specific biomarker of liver function, a key parameter in the context of post-partum negative energy balance in dairy cows

Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury

[EN] Objectives Acquired brain injury (ABI) can lead to the emergence of several disabilities and is commonly associated with high rates of anxiety and depression symptoms. Self-related constructs, such as self-esteem and self-compassion, might play a key role in this distressing symptomatology. Low explicit (i.e., deliberate) self-esteem is associated with anxiety and depression after ABI. However, implicit (i.e., automatic) self-esteem, explicit-implicit self-discrepancies, and self-compassion could also significantly contribute to this symptomatology. The purpose of the present study was to examine whether implicit self-esteem, explicit-implicit self-discrepancy (size and direction), and self-compassion are related to anxious and depressive symptoms after ABI in adults, beyond the contribution of explicit self-esteem. Methods The sample consisted 38 individuals with ABI who were enrolled in a long-term rehabilitation program. All participants completed the measures of explicit self-esteem, implicit self-esteem, self-compassion, anxiety, and depression. Pearson's correlations and hierarchical regression models were calculated. Results Findings showed that both self-compassion and implicit self-esteem negatively accounted for unique variance in anxiety and depression when controlling for explicit self-esteem. Neither the size nor direction of explicit-implicit self-discrepancy was significantly associated with anxious or depressive symptomatology. Conclusions The findings suggest that the consideration of self-compassion and implicit self-esteem, in addition to explicit self-esteem, contributes to understanding anxiety and depression following ABI.Lorena Desdentado is supported by a FPU doctoral scholarship (FPU18/01690) from the Spanish Ministry of Universities. This work was supported by CIBEROBN, an initiative of the ISCIII (ISC III CB06 03/0052).Desdentado, L.; Cebolla, A.; Miragall, M.; Llorens Rodríguez, R.; Navarro, MD.; Baños, RM. (2021). Exploring the Role of Explicit and Implicit Self-Esteem and Self-Compassion in Anxious and Depressive Symptomatology Following Acquired Brain Injury. Mindfulness. 12(4):899-910. https://doi.org/10.1007/s12671-020-01553-wS899910124Anson, K., & Ponsford, J. (2006). Coping and emotional adjustment following traumatic brain injury. The Journal of Head Trauma Rehabilitation, 21(3), 248–259. https://doi.org/10.1097/00001199-200605000-00005.Baños, R. M., & Guillén, V. (2000). Psychometric characteristics in normal and social phobic samples for a Spanish version of the Rosenberg Self-Esteem Scale. Psychological Reports, 87(1), 269–274. https://doi.org/10.2466/pr0.2000.87.1.269.Beadle, E. J., Ownsworth, T., Fleming, J., & Shum, D. (2016). The impact of traumatic brain injury on self-identity: a systematic review of the evidence for self-concept changes. The Journal of Head Trauma Rehabilitation, 31(2), E12–E25. https://doi.org/10.1097/HTR.0000000000000158.Beck, A. T. (1979). Cognitive therapy of depression. New York: Guilford Press.Beevers, C. G. (2005). Cognitive vulnerability to depression: A dual process model. Clinical Psychology Review, 25(7), 975–1002. https://doi.org/10.1016/j.cpr.2005.03.003.Bos, A. E. R., Huijding, J., Muris, P., Vogel, L. R. R., & Biesheuvel, J. (2010). Global, contingent and implicit self-esteem and psychopathological symptoms in adolescents. Personality and Individual Differences, 48(3), 311–316. https://doi.org/10.1016/j.paid.2009.10.025.Bowerman, B. L., & O’Connell, R. T. (1990). Linear statistical models: An applied approach (2nd ed.). Belmont, CA: Duxbury.Brenner, R. E., Heath, P. J., Vogel, D. L., & Credé, M. (2017). Two is more valid than one: examining the factor structure of the self-compassion scale (SCS). Journal of Counseling Psychology, 64(6), 696–707. https://doi.org/10.1037/cou0000211.Brysbaert, M. (2019). How many participants do we have to include in properly powered experiments? A tutorial of power analysis with reference tables. Journal of Cognition, 2(1), 1–38. https://doi.org/10.5334/joc.72.Carroll, E., & Coetzer, R. (2011). Identity, grief and self-awareness after traumatic brain injury. Neuropsychological Rehabilitation, 21(3), 289–305. https://doi.org/10.1080/09602011.2011.555972.Corrigan, P. W., & Watson, A. C. (2002). The paradox of self-stigma and mental illness. Clinical Psychology: Science and Practice, 9(1), 35–53. https://doi.org/10.1093/clipsy/9.1.35.Creemers, D. H. M., Scholte, R. H. J., Engels, R. C. M. E., Prinstein, M. J., & Wiers, R. W. (2012). Implicit and explicit self-esteem as concurrent predictors of suicidal ideation, depressive symptoms, and loneliness. Journal of Behavior Therapy and Experimental Psychiatry, 43(1), 638–646. https://doi.org/10.1016/j.jbtep.2011.09.006.Creemers, D. H. M., Scholt, R. H. J., Engels, R. C. M. E., Prinstein, M. J., & Wiers, R. W. (2013). Damaged self-esteem is associated with internalizing problems. Frontiers in Psychology, 4, 152. https://doi.org/10.3389/fpsyg.2013.00152.Curvis, W., Simpson, J., & Hampson, N. (2018). Factors associated with self-esteem following acquired brain injury in adults: a systematic review. Neuropsychological Rehabilitation, 28(1), 142–183. https://doi.org/10.1080/09602011.2016.1144515.Elbaum, J., & Benson, D. (Eds.). (2007). Acquired brain injury: an integrative neuro-rehabilitation approach. New York: Springer. https://doi.org/10.1007/978-0-387-37575-5.Faul, F., Erdfelder, E., Buchner, A., & Lang, A.-G. (2009). Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41(4), 1149–1160. https://doi.org/10.3758/BRM.41.4.1149.FEDACE. (2015). Las personas con daño cerebral adquirido en España. Ministerio de Sanidad, Servicios Sociales e Igualdad. Retrieved May 21, 2020, from: https://fedace.org/index.php?V_dir=MSC&V_mod=download&f=2016-9/26-16-4-11.admin.Informe_FEDACE_RPD_para_DDC-1.pdf.Feigin, V. L., Forouzanfar, M. H., Krishnamurthi, R., Mensah, G. A., Connor, M., Bennett, D. A., Moran, A. E., Sacco, R. L., Anderson, L., Truelsen, T., O’Donnell, M., Venketasubramanian, N., Barker-Collo, S., Lawes, C. M. M., Wang, W., Shinohara, Y., Witt, E., Ezzati, M., & Naghavi, M. (2014). Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. The Lancet, 383(9913), 245–254. https://doi.org/10.1016/S0140-6736(13)61953-4.Fennell, M. J. V. (1997). Low self-esteem: a cognitive perspective. Behavioural and Cognitive Psychotherapy, 25(1), 1–26. https://doi.org/10.1017/s1352465800015368.Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. https://doi.org/10.1016/0022-3956(75)90026-6.Garcia-Campayo, J., Navarro-Gil, M., Andrés, E., Montero-Marin, J., López-Artal, L., Marcos, M., & Demarzo, P. (2014). Validation of the Spanish versions of the long (26 items) and short (12 items) forms of the Self-Compassion Scale (SCS). Health and Quality of Life Outcomes, 12(4). https://doi.org/10.1186/1477-7525-12-4.GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. (2018). Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 18(1), 56–87. https://doi.org/10.1016/S1474-4422(18)30415-0.Gould, K. R., Ponsford, J. L., Johnston, L., & Schönberger, M. (2011). Relationship between psychiatric disorders and 1-year psychosocial outcome following traumatic brain injury. The Journal of Head Trauma Rehabilitation, 26(1), 79–89. https://doi.org/10.1097/HTR.0b013e3182036799.Gracey, F., Palmer, S., Rous, B., Psaila, K., Shaw, K., O’Dell, J., Cope, J., & Mohamed, S. (2008). “Feeling part of things”: personal construction of self after brain injury. Neuropsychological Rehabilitation, 18(5–6), 627–650. https://doi.org/10.1080/09602010802041238.Gracey, F., Evans, J. J., & Malley, D. (2009). Capturing process and outcome in complex rehabilitation interventions: a “Y-shaped” model. Neuropsychological Rehabilitation, 19(6), 867–890. https://doi.org/10.1080/09602010903027763.Greenwald, A. G., & Farnham, S. D. (2000). Using the Implicit Association Test to measure self-esteem and self-concept. Journal of Personality and Social Psychology, 79(6), 1022–1038. https://doi.org/10.1037/0022-3514.79.6.1022.Greenwald, A. G., McGhee, D. E., & Schwartz, J. L. K. (1998). Measuring individual differences in implicit cognition: the Implicit Association Test. Journal of Personality and Social Psychology, 74(6), 1464–1480. https://doi.org/10.1037/0022-3514.74.6.1464.Greenwald, A. G., Nosek, B. A., & Banaji, M. R. (2003). Understanding and using the Implicit Association Test: I. An improved scoring algorithm. Journal of Personality and Social Psychology, 85(2), 197–216. https://doi.org/10.1037/0022-3514.85.2.197.Hackett, M. L., Yapa, C., Parag, V., & Anderson, C. S. (2005). Frequency of depression after stroke: a systematic review of observational studies. Stroke, 36(6), 1330–1340. https://doi.org/10.1161/01.STR.0000165928.19135.35.Haeffel, G. J., Abramson, L. Y., Brazy, P. C., Shah, J. Y., Teachman, B. A., & Nosek, B. A. (2007). Explicit and implicit cognition: a preliminary test of a dual-process theory of cognitive vulnerability to depression. Behaviour Research and Therapy, 45(6), 1155–1167. https://doi.org/10.1016/j.brat.2006.09.003.Ingram, R. E. (1984). Toward an information-processing analysis of depression. Cognitive Therapy and Research, 8(5), 443–477. https://doi.org/10.1007/BF01173284.Izuma, K., Kennedy, K., Fitzjohn, A., Sedikides, C., & Shibata, K. (2018). Neural activity in the reward-related brain regions predicts implicit self-esteem: a novel validity test of psychological measures using neuroimaging. Journal of Personality and Social Psychology, 114(3), 343–357. https://doi.org/10.1037/pspa0000114.Khan-Bourne, N., & Brown, R. G. (2003). Cognitive behaviour therapy for the treatment of depression in individuals with brain injury. Neuropsychological Rehabilitation, 13(1–2), 89–107. https://doi.org/10.1080/09602010244000318.Kim, H. S., & Moore, M. T. (2019). Symptoms of depression and the discrepancy between implicit and explicit self-esteem. Journal of Behavior Therapy and Experimental Psychiatry, 63, 1–5. https://doi.org/10.1016/j.jbtep.2018.12.001.Lane, K. A., Banaji, M. R., Nosek, B. A., & Greenwald, A. G. (2007). Understanding and using the Implicit Association Test: IV. What we know (so far) about the method. In B. Wittenbrink & N. Schwarz (Eds.), Implicit measures of attitudes (pp. 59–102). New York: The Guildford Press.Leary, M. R., Tate, E. B., Adams, C. E., Batts Allen, A., & Hancock, J. (2007). Self-compassion and reactions to unpleasant self-relevant events: the implications of treating oneself kindly. Personality Processes and Individual Differences, 92(5), 887–904. https://doi.org/10.1037/0022-3514.92.5.887.Lennon, A., Bramham, J., Carroll, À., McElligott, J., Carton, S., Waldron, B., Fortune, D., Burke, T., Fitzhenry, M., & Benson, C. (2014). A qualitative exploration of how individuals reconstruct their sense of self following acquired brain injury in comparison with spinal cord injury. Brain Injury, 28(1), 27–37. https://doi.org/10.3109/02699052.2013.848378.Longworth, C., Deakins, J., Rose, D., & Gracey, F. (2018). The nature of self-esteem and its relationship to anxiety and depression in adult acquired brain injury. Neuropsychological Rehabilitation, 28(7), 1078–1094. https://doi.org/10.1080/09602011.2016.1226185.MacBeth, A., & Gumley, A. (2012). Exploring compassion: a meta-analysis of the association between self-compassion and psychopathology. Clinical Psychology Review, 32(6), 545–552. https://doi.org/10.1016/j.cpr.2012.06.003.McDonald, S., Saad, A., & James, C. (2011). Social dysdecorum following severe traumatic brain injury: loss of implicit social knowledge or loss of control? Journal of Clinical and Experimental Neuropsychology, 33(6), 619–630. https://doi.org/10.1080/13803395.2011.553586.Milne, E., & Grafman, J. (2001). Ventromedial prefrontal cortex lesions in humans eliminate implicit gender stereotyping. The Journal of Neuroscience, 21(12), 1–6.Moors, A., & De Houwer, J. (2006). Automaticity: a theoretical and conceptual analysis. Psychological Bulletin, 132(2), 297–326. https://doi.org/10.1037/0033-2909.132.2.297.Muris, P., & Petrocchi, N. (2017). Protection or vulnerability? A meta-analysis of the relations between the positive and negative components of self-compassion and psychopathology. Clinical Psychology & Psychotherapy, 24(2), 373–383. https://doi.org/10.1002/cpp.2005.Myers, R. (2000). Classical and modern regression with applications (2nd ed.). Belmont, CA: Duxbury.Neff, K. D. (2003). Self-compassion: an alternative conceptualization of a healthy attitude toward oneself. Self and Identity, 2(2), 85–101. https://doi.org/10.1080/15298860309032.Neff, K. D., & Vonk, R. (2009). Self-compassion versus global self-esteem: two different ways of relating to oneself. Journal of Personality, 77, 23–50. https://doi.org/10.1111/j.1467-6494.2008.00537.x.Neff, K. D., Tóth-Király, I., Yarnell, L. M., Arimitsu, K., Castilho, P., Ghorbani, N., Guo, H. X., Hirsch, J. K., Hupfeld, J., Hutz, C. S., Kotsou, I., Lee, W. K., Montero-Marin, J., Sirois, F. M., De Souza, L. K., Svendsen, J. L., Wilkinson, R. B., & Mantzios, M. (2019). Examining the factor structure of the Self-Compassion Scale in 20 diverse samples: support for use of a total score and six subscale scores. Psychological Assessment, 31(1), 27–45. https://doi.org/10.1037/pas0000629.Norton, P. J., & Paulus, D. J. (2017). Transdiagnostic models of anxiety disorder: theoretical and empirical underpinnings. Clinical Psychology Review, 56, 122–137. https://doi.org/10.1016/j.cpr.2017.03.004.Nosek, B. A., & Banaji, M. R. (2001). The go/no-go association task. Social Cognition, 19(6), 625–664. https://doi.org/10.1521/soco.19.6.625.20886.Oddy, M., & Herbert, C. (2003). Intervention with families following brain injury: evidence-based practice. Neuropsychological Rehabilitation, 13(1–2), 259–273. https://doi.org/10.1080/09602010244000345.Ouimet, A. J., Gawronski, B., & Dozois, D. J. A. (2009). Cognitive vulnerability to anxiety: a review and an integrative model. Clinical Psychology Review, 29(6), 459–470. https://doi.org/10.1016/j.cpr.2009.05.004.Ponsford, J., Kelly, A., & Couchman, G. (2014). Self-concept and self-esteem after acquired brain injury: a control group comparison. Brain Injury, 28(2), 146–154. https://doi.org/10.3109/02699052.2013.859733.Raes, F., Pommier, E., Neff, K. D., & Van Gucht, D. (2011). Construction and factorial validation of a short form of the Self-Compassion Scale. Clinical Psychology & Psychotherapy, 18(3), 250–255. https://doi.org/10.1002/cpp.702.Romero, M., Sánchez, A., Marín, C., Navarro, M. D., Ferri, J., & Noé, E. (2012). Clinical usefulness of the Spanish version of the Mississippi Aphasia Screening Test (MASTsp): validation in stroke patients. Neurología (English Edition), 27(4), 216–224. https://doi.org/10.1016/j.nrleng.2011.06.001.Rosenberg, M. (1965). Rosenberg Self-Esteem Scale (RSE). Acceptance and Commitment Therapy. Measures Package, 61, 52 /S0034-98872009000600009.Sandstrom, M. J., & Jordan, R. (2008). Defensive self-esteem and aggression in childhood. Journal of Research in Personality, 42(2), 506–514. https://doi.org/10.1016/j.jrp.2007.07.008.Schönberger, M., & Ponsford, J. (2010). The factor structure of the Hospital Anxiety and Depression Scale in individuals with traumatic brain injury. Psychiatry Research, 179(3), 342–349. https://doi.org/10.1016/j.psychres.2009.07.003.Schröder-Abé, M., Rudolph, A., & Schütz, A. (2007). High implicit self-esteem is not necessarily advantageous: discrepancies between explicit and implicit self-esteem and their relationship with anger expression and psychological health. European Journal of Personality, 21(3), 319–339. https://doi.org/10.1002/per.626.Scoglio, A. A. J., Rudat, D. A., Garvert, D., Jarmolowski, M., Jackson, C., & Herman, J. L. (2018). Self-compassion and responses to trauma: the role of emotion regulation. Journal of Interpersonal Violence, 33(13), 2016–2036. https://doi.org/10.1177/0886260515622296.Sloan, E., Hall, K., Moulding, R., Bryce, S., Mildred, H., & Staiger, P. K. (2017). Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: a systematic review. Clinical Psychology Review, 57, 141–163. https://doi.org/10.1016/j.cpr.2017.09.002.Smeijers, D., Vrijsen, J. N., van Oostrom, I., Isaac, L., Speckens, A., Becker, E. S., & Rinck, M. (2017). Implicit and explicit self-esteem in remitted depressed patients. Journal of Behavior Therapy and Experimental Psychiatry, 54, 301–306. https://doi.org/10.1016/j.jbtep.2016.10.006.Smith, E. R., & DeCoster, J. (2000). Dual-process models in social and cognitive psychology: conceptual integration and links to underlying memory systems. Personality and Social Psychology Review, 4(2), 108–131. https://doi.org/10.1207/S15327957PSPR0402_01.Sowislo, J. F., & Orth, U. (2013). Does low self-esteem predict depression and anxiety? A meta-analysis of longitudinal studies. Psychological Bulletin, 139(1), 213–240. https://doi.org/10.1037/a0028931.Strack, F., & Deutsch, R. (2004). Reflective and impulsive determinants of social behavior. Personality and Social Psychology Review, 8(3), 220–247. https://doi.org/10.1207/s15327957pspr0803_1.Terol-Cantero, M. C., Cabrera-Perona, V., & Martín-Aragón, M. (2015). Hospital Anxiety and Depression Scale (HADS) review in Spanish samples. Anales de Psicología, 31(2), 494–503. https://doi.org/10.6018/analesps.31.2.172701.Tóth-Király, I., & Neff, K. D. (2020). Is self-compassion universal? Support for the measurement invariance of the Self-Compassion Scale across populations. Assessment. Advance online publication. https://doi.org/10.1177/1073191120926232.Turner-Stokes, L., & Wade, D. (2003). Rehabilitation following acquired brain injury: National Clinical Guidelines. Clinical Medicine, 4(1), 61–65. https://doi.org/10.7861/clinmedicine.4-1-61.Tyerman, A., & Humphrey, M. (1984). Changes in self-concept following severe head injury. International Journal of Rehabilitation Research, 7(1), 11–23. https://doi.org/10.1097/00004356-198403000-00002.Valiente, C., Cantero, D., Vázquez, C., Sanchez, Á., Provencio, M., & Espinosa, R. (2011). Implicit and explicit self-esteem discrepancies in paranoia and depression. Journal of Abnormal Psychology, 120(3), 691–699. https://doi.org/10.1037/a0022856.Vickery, C. D., Sepehri, A., & Evans, C. C. (2008). Self-esteem in an acute stroke rehabilitation sample: a control group comparison. Clinical Rehabilitation, 22(2), 179–187. https://doi.org/10.1177/0269215507080142.Whelan-Goodinson, R., Ponsford, J., & Schönberger, M. (2009). Validity of the Hospital Anxiety and Depression Scale to assess depression and anxiety following traumatic brain injury as compared with the Structured Clinical Interview for DSM-IV. Journal of Affective Disorders, 114(1–3), 94–102. https://doi.org/10.1016/j.jad.2008.06.007.Zeigler-Hill, V. (2006). Discrepancies between implicit and explicit self-esteem: Implications for narcissism and self-esteem instability. Journal of Personality, 74(1), 119–144. https://doi.org/10.1111/j.1467-6494.2005.00371.x.Zessin, U., Dickhäuser, O., & Garbade, S. (2015). The relationship between self-compassion and well-being: a meta-analysis. Applied Psychology. Health and Well-Being, 7(3), 340–364. https://doi.org/10.1111/aphw.12051.Zhang, J. W., Chen, S., & Tomova Shakur, T. K. (2020). From me to you: Self-compassion predicts acceptance of own and others’ imperfections. Personality and Social Psychology Bulletin, 46(2), 228–242. https://doi.org/10.1177/0146167219853846.Zigmond, A. S., & Snaith, R. P. (1983). The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica, 67(6), 361–370. https://doi.org/10.1111/j.1600-0447.1983.tb09716.x

Autocatalytic Activation of the Furin Zymogen Requires Removal of the Emerging Enzyme's N-Terminus from the Active Site

Before furin can act on protein substrates, it must go through an ordered process of activation. Similar to many other proteinases, furin is synthesized as a zymogen (profurin) which becomes active only after the autocatalytic removal of its auto-inhibitory prodomain. We hypothesized that to activate profurin its prodomain had to be removed and, in addition, the emerging enzyme's N-terminus had to be ejected from the catalytic cleft.We constructed and analyzed the profurin mutants in which the egress of the emerging enzyme's N-terminus from the catalytic cleft was restricted. Mutants were autocatalytically processed at only the primary cleavage site Arg-Thr-Lys-Arg(107) downward arrowAsp(108), but not at both the primary and the secondary (Arg-Gly-Val-Thr-Lys-Arg(75) downward arrowSer(76)) cleavage sites, yielding, as a result, the full-length prodomain and mature furins commencing from the N-terminal Asp108. These correctly processed furin mutants, however, remained self-inhibited by the constrained N-terminal sequence which continuously occupied the S' sub-sites of the catalytic cleft and interfered with the functional activity. Further, using the in vitro cleavage of the purified prodomain and the analyses of colon carcinoma LoVo cells with the reconstituted expression of the wild-type and mutant furins, we demonstrated that a three-step autocatalytic processing including the cleavage of the prodomain at the previously unidentified Arg-Leu-Gln-Arg(89) downward arrowGlu(90) site, is required for the efficient activation of furin.Collectively, our results show the restrictive role of the enzyme's N-terminal region in the autocatalytic activation mechanisms. In a conceptual form, our data apply not only to profurin alone but also to a range of self-activated proteinases

Zebrafish ProVEGF-C Expression, Proteolytic Processing and Inhibitory Effect of Unprocessed ProVEGF-C during Fin Regeneration

BACKGROUND: In zebrafish, vascular endothelial growth factor-C precursor (proVEGF-C) processing occurs within the dibasic motif HSIIRR(214) suggesting the involvement of one or more basic amino acid-specific proprotein convertases (PCs) in this process. In the present study, we examined zebrafish proVEGF-C expression and processing and the effect of unprocessed proVEGF-C on caudal fin regeneration. METHODOLOGY/PRINCIPAL FINDINGS: Cell transfection assays revealed that the cleavage of proVEGF-C, mainly mediated by the proprotein convertases Furin and PC5 and to a less degree by PACE4 and PC7, is abolished by PCs inhibitors or by mutation of its cleavage site (HSIIRR(214) into HSIISS(214)). In vitro, unprocessed proVEGF-C failed to activate its signaling proteins Akt and ERK and to induce cell proliferation. In vivo, following caudal fin amputation, the induction of VEGF-C, Furin and PC5 expression occurs as early as 2 days post-amputation (dpa) with a maximum levels at 4-7 dpa. Using immunofluorescence staining we localized high expression of VEGF-C and the convertases Furin and PC5 surrounding the apical growth zone of the regenerating fin. While expression of wild-type proVEGF-C in this area had no effect, unprocessed proVEGF-C inhibited fin regeneration. CONCLUSIONS/SIGNIFICANCES: Taken together, these data indicate that zebrafish fin regeneration is associated with up-regulation of VEGF-C and the convertases Furin and PC5 and highlight the inhibitory effect of unprocessed proVEGF-C on fin regeneration

Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We investigated the kinetics of the killing of antibiotic-resistant bacteria by RS honey, the source for the production of Revamil® medical-grade honey, and we aimed to enhance the rapid bactericidal activity of RS honey by enrichment with its endogenous compounds or the addition of antimicrobial peptides (AMPs). RS honey killed antibiotic-resistant isolates of Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus faecium, and Burkholderia cepacia within 2 h, but lacked such rapid activity against methicillin-resistant S. aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. It was not feasible to enhance the rapid activity of RS honey by enrichment with endogenous compounds, but RS honey enriched with 75 μM of the synthetic peptide Bactericidal Peptide 2 (BP2) showed rapid bactericidal activity against all species tested, including MRSA and ESBL E. coli, at up to 10–20-fold dilution. RS honey enriched with BP2 rapidly killed all bacteria tested and had a broader spectrum of bactericidal activity than either BP2 or honey alone

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications

Small-animal SPECT and SPECT/CT: application in cardiovascular research

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease