Structural basis for the recognition and cleavage of histone H3 by cathepsin L

Proteolysis of eukaryotic histone tails has emerged as an important factor in the modulation of cell-cycle progression and cellular differentiation. The recruitment of lysosomal cathepsin L to the nucleus where it mediates proteolysis of the mouse histone H3 tail has been described recently. Here, we report the three-dimensional crystal structures of a mature, inactive mutant of human cathepsin L alone and in complex with a peptide derived from histone H3. Canonical substrate–cathepsin L interactions are observed in the complex between the protease and the histone H3 peptide. Systematic analysis of the impact of posttranslational modifications at histone H3 on substrate selectivity suggests cathepsin L to be highly accommodating of all modified peptides. This is the first report of cathepsin L–histone H3 interaction and the first structural description of cathepsin L in complex with a substrate

Chromatin compaction in terminally differentiated avian blood cells: the role of linker histone H5 and non-histone protein MENT

Chromatin has a tendency to shift from a relatively decondensed (active) to condensed (inactive) state during cell differentiation due to interactions of specific architectural and/or regulatory proteins with DNA. A promotion of chromatin folding in terminally differentiated avian blood cells requires the presence of either histone H5 in erythrocytes or non-histone protein, myeloid and erythroid nuclear termination stage-specific protein (MENT), in white blood cells (lymphocytes and granulocytes). These highly abundant proteins assist in folding of nucleosome arrays and self-association of chromatin fibers into compacted chromatin structures. Here, we briefly review structural aspects and molecular mode of action by which these unrelated proteins can spread condensed chromatin to form inactivated regions in the genome

Psychological considerations in the assessment and treatment of pain in neurorehabilitation and psychological factors predictive of therapeutic response: Evidence and recommendations from the Italian consensus conference on pain in neurorehabilitation

In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics

Agonistic behavior of the termite Prorhinotermes canalifrons (Isoptera: Rhinotermitidae)

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Time for a consensus conference on pain in neurorehabilitation

Time for a Consensus Conference on pain in neurorehabilitation

Time for a consensus conference on pain in neurorehabilitation

O uso do enxerto autólogo de gordura ou lipoenxertia (termo em inglês - “lipofilling”) na reconstrução imediata da cirurgia conservadora de mama vem sendo aplicada a fim de atingir resultado estético satisfatório na primeira cirurgia para o câncer de mama em pacientes com relação tumor/mama desfavorável ou em localização de difícil reparo. A segurança oncológica da técnica ainda é discutida devido ao pouco número de pacientes em seguimento. Objetivo: determinar se há diferença nas taxas de recidiva local e sobrevida livre de doença em relação à realização ou não de lipoenxertia imediata na cirurgia conservadora. Metodologia: Foram selecionados retrospectivamente os pacientes submetidos à cirurgia conservadora com ou sem lipoenxertia entre 2004 e 2016. Os grupos foram pareados por idade, estadiamento, grau e perfil imuno-histoquímico do tumor. Os pacientes foram acompanhados por uma média de 60 meses e as taxas de recorrência e sobrevida livre de doença foram avaliadas. Resultados: 320 pacientes acompanhadas, casos pareados com controles na proporção de 1:4. Não foram observadas diferenças significativas na recorrência loco-regional (LRR) das pacientes que foram submetidas à lipoenxertia simultaneamente à cirurgia conservadora em comparação com os controles, LRR 0,86% ao ano x 0,70% ao ano, p => 0,05, respectivamente. Não houve diferenças na sobrevida livre de doença entre os grupos. Conclusão: Após 60 meses de seguimento, não houve diferença significativa nas taxas de recorrência loco-regional entre o grupo de lipoenxertia imediata e o grupo controle. Esses achados sugerem a segurança oncológica da reconstrução imediata com a lipoenxertia, propondo a técnica como eficaz, segura e com ótimo resultado estético para o câncer de mama.Importance: Autologous fat grafting (AFG), or lipofilling, has been used for immediate reconstruction at the time of breast-conserving surgery in order to achieve a satisfactory cosmetic outcome in patients with breast cancer and an unfavorable tumor-to-breast volume ratio or unfavorable tumor location. However, the oncologic safety of this technique is still unclear. Objective: To determine whether AFG performed simultaneously with breast-conserving surgery is associated with differences in local relapse rates and disease-free survival. Design: Matched retrospective cohort study. Setting: Tertiary referral center. Participants: Patients undergoing breast-conserving surgery with or without AFG between 2004 and 2016 were retrospectively enrolled and matched for age, staging, grade, tumor histology, and tumor immunohistochemical profile. Main Outcome(s) And Measure(s): The cumulative incidence of locoregional recurrence (LRR) and disease-free survival were the primary end points, while distant recurrence and overall survival were the secondary end points. Results: A total of 320 patients were followed. Cases were matched with controls at a 1:4 ratio. There was no difference in LRR or distant recurrence of breast cancer between the two groups. The annual LRR rate was 0.86% in patients who received immediate AFG vs. 0.7% in patients undergoing breast-conserving surgery alone (P≥0.05). Number of lymph nodes was the sole independent risk factor for local recurrence (p=0.045). No significant differences in disease-free survival rates were found between the groups. Conclusions and Relevance: At a mean follow-up of 5 years, no significant differences in locoregional recurrence rates were found between patients who received immediate AFG and those who underwent breast-conserving surgery alone. These findings corroborate previous research demonstrating the oncological safety of immediate AFG reconstruction, further suggesting that this technique as a safe, effective way to achieve optimal cosmetic outcomes in primary breast cancer surgery without jeopardizing oncologic outcomes

Time for a Consensus Conference on pain in neurorehabilitation

Time for a Consensus Conference on pain in neurorehabilitation