Feedback control of chromosome separation by a midzone Aurora B gradient

Accurate chromosome segregation during mitosis requires the physical separation of sister chromatids before nuclear envelope reassembly (NER). However, how these two processes are coordinated remains unknown. Here, we identified a conserved feedback control mechanism that delays chromosome decondensation and NER in response to incomplete chromosome separation during anaphase. A midzone-associated Aurora B gradient was found to monitor chromosome position along the division axis and to prevent premature chromosome decondensation by retaining Condensin I. PP1/PP2A phosphatases counteracted this gradient and promoted chromosome decondensation and NER. Thus, an Aurora B gradient appears to mediate a surveillance mechanism that prevents chromosome decondensation and NER until effective separation of sister chromatids is achieved. This allows the correction and reintegration of lagging chromosomes in the main nuclei before completion of NER.We thank all colleagues who provided reagents and P. Sampaio for technical help with FRET. H. M. is funded by FCOMP-01-0124-FEDER-015941 (PTDC/SAU-ONC/112917/2009) through COMPETE and Fundacao para a Ciencia e a Tecnologia of Portugal, the Human Frontier Science Program, and PRECISE grant from the European Research Council. Data described can be found in the main figures and supplementary materials. The authors declare no conflict of interests

Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading

<p>Abstract</p> <p>Background</p> <p>Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor.</p> <p>Methods</p> <p>In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated.</p> <p>Results</p> <p>The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma.</p> <p>Conclusion</p> <p>The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.</p

Risks and benefits of sharing patient information on social media: a digital dilemma

Social media (SoMe) has witnessed remarkable growth and emerged as a dominant method of communication worldwide. Platforms such as Facebook, X (formerly Twitter), LinkedIn, Instagram, TikTok, and YouTube have become important tools of the digital native generation. In the field of medicine, particularly, cardiology, attitudes towards SoMe have shifted, and professionals increasingly utilize it to share scientific findings, network with experts, and enhance teaching and learning. Notably, SoMe is being leveraged for teaching purposes, including the sharing of challenging and intriguing cases. However, sharing patient data, including photos or images, online carries significant implications and risks, potentially compromising individual privacy both online and offline. Privacy and data protection are fundamental rights within European Union treaties, and the General Data Protection Regulation (GDPR) serves as the cornerstone of data protection legislation. The GDPR outlines crucial requirements, such as obtaining ‘consent’ and implementing ‘anonymization’, that must be met before sharing sensitive and patient-identifiable information. Additionally, it is vital to consider the patient’s perspective and prioritize ethical and social considerations when addressing challenges associated with sharing patient information on SoMe platforms. Given the absence of a peer-review process and clear guidelines, we present an initial approach, a code of conduct, and recommendations for the ethical use of SoMe. In conclusion, this comprehensive review underscores the importance of a balanced approach that ensures patient privacy and upholds ethical standards while harnessing the immense potential of SoMe to advance cardiology practice and facilitate knowledge dissemination

Numerical relations and skill level constrain co-adaptive behaviors of agents in sports teams

Similar to other complex systems in nature (e.g., a hunting pack, flocks of birds), sports teams have been modeled as social neurobiological systems in which interpersonal coordination tendencies of agents underpin team swarming behaviors. Swarming is seen as the result of agent co-adaptation to ecological constraints of performance environments by collectively perceiving specific possibilities for action (affordances for self and shared affordances). A major principle of invasion team sports assumed to promote effective performance is to outnumber the opposition (creation of numerical overloads) during different performance phases (attack and defense) in spatial regions adjacent to the ball. Such performance principles are assimilated by system agents through manipulation of numerical relations between teams during training in order to create artificially asymmetrical performance contexts to simulate overloaded and underloaded situations. Here we evaluated effects of different numerical relations differentiated by agent skill level, examining emergent inter-individual, intra- and inter-team coordination. Groups of association football players (national - NLP and regional-level - RLP) participated in small-sided and conditioned games in which numerical relations between system agents were manipulated (5v5, 5v4 and 5v3). Typical grouping tendencies in sports teams (major ranges, stretch indices, distances of team centers to goals and distances between the teams' opposing line-forces in specific team sectors) were recorded by plotting positional coordinates of individual agents through continuous GPS tracking. Results showed that creation of numerical asymmetries during training constrained agents' individual dominant regions, the underloaded teams' compactness and each team's relative position on-field, as well as distances between specific team sectors. We also observed how skill level impacted individual and team coordination tendencies. Data revealed emergence of co-adaptive behaviors between interacting neurobiological social system agents in the context of sport performance. Such observations have broader implications for training design involving manipulations of numerical relations between interacting members of social collectives

Pervasive transition of the Brazilian land-use system

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Crystal structure of tarocystatin–papain complex: implications for the inhibition property of group-2 phytocystatins

Tarocystatin (CeCPI) from taro (Colocasia esculenta cv. Kaohsiung no. 1), a group-2 phytocystatin, shares a conserved N-terminal cystatin domain (NtD) with other phytocystatins but contains a C-terminal cystatin-like extension (CtE). The structure of the tarocystatin–papain complex and the domain interaction between NtD and CtE in tarocystatin have not been determined. We resolved the crystal structure of the phytocystatin–papain complex at resolution 2.03 Å. Surprisingly, the structure of the NtD–papain complex in a stoichiometry of 1:1 could be built, with no CtE observed. Only two remnant residues of CtE could be built in the structure of the CtE–papain complex. Therefore, CtE is easily digested by papain. To further characterize the interaction between NtD and CtE, three segments of tarocystatin, including the full-length (FL), NtD and CtE, were used to analyze the domain–domain interaction and the inhibition ability. The results from glutaraldehyde cross-linking and yeast two-hybrid assay indicated the existence of an intrinsic flexibility in the region linking NtD and CtE for most tarocystatin molecules. In the inhibition activity assay, the glutathione-S-transferase (GST)-fused FL showed the highest inhibition ability without residual peptidase activity, and GST-NtD and FL showed almost the same inhibition ability, which was higher than with NtD alone. On the basis of the structures, the linker flexibility and inhibition activity of tarocystatins, we propose that the overhangs from the cystatin domain may enhance the inhibition ability of the cystatin domain against papain

Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase

The APOBEC3 proteins form a multigene family of cytidine deaminases with inhibitory activity against viruses and retrotransposons. In contrast to APOBEC3G (A3G), APOBEC3A (A3A) has no effect on lentiviruses but dramatically inhibits replication of the parvovirus adeno-associated virus (AAV). To study the contribution of deaminase activity to the antiviral activity of A3A, we performed a comprehensive mutational analysis of A3A. By mutation of non-conserved residues, we found that regions outside of the catalytic active site contribute to both deaminase and antiviral activities. Using A3A point mutants and A3A/A3G chimeras, we show that deaminase activity is not required for inhibition of recombinant AAV production. We also found that deaminase-deficient A3A mutants block replication of both wild-type AAV and the autonomous parvovirus minute virus of mice (MVM). In addition, we identify specific residues of A3A that confer activity against AAV when substituted into A3G. In summary, our results demonstrate that deaminase activity is not necessary for the antiviral activity of A3A against parvoviruses

The Bandim TBscore – reliability, further development, and evaluation of potential uses

Background: The tuberculosis (TB) case detection rate has stagnated at 60% due to disorganized case finding and insensitivity of sputum smear microscopy. Of the identified TB cases, 4% die while being treated, monitored with tools that insufficiently predict failure/mortality. Objective: To explore the TBscore, a recently proposed clinical severity measure for pulmonary TB (PTB) patients, and to refine, validate, and investigate its place in case finding. Design: The TBscore's inter-observer agreement was assessed and compared to the Karnofsky Performance Score (KPS) (paper I). The TBscore's variables underlying constructs were assessed, sorting out unrelated items, proposing a more easily assessable TBscoreII, which was validated internally and externally (paper II). Finally, TBscore and TBscoreII's place in PTB-screening was examined in paper III. Results: The inter-observer variability when grading PTB patients into severity classes was moderate for both TBscore (κ W=0.52, 95% CI 0.46–0.56) and KPS (κ W=0.49, 95% CI 0.33–0.65). KPS was influenced by HIV status, whereas TBscore was unaffected by it. In paper II, proposed TBscoreII was validated internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a failure to bring down the score by ≥25% from baseline to 2 months of treatment predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and TBscoreII were assessed in health-care-seeking adults and found to be higher in PTB-diagnosed patients, 4.9 (95% CI 4.6–5.2) and 3.9 (95% CI 3.8–4.0), respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7–3.2) and 2.4 (95% CI 2.3–2.5), respectively. Had we referred only patients with cough >2 weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in our cohort. A TBscoreII>=2 missed 8.6%. Conclusions: TBscore and TBscoreII are useful monitoring tools for PTB patients on treatment, as they could fill the void which currently exists in risk grading of patients. They may also have a role in PTB screening; however, this requires our findings to be repeated elsewhere