Entropy based analysis of vertebrate sperm protamines sequences: evidence of potential dityrosine and cysteine-tyrosine cross-linking in sperm protamines.

BACKGROUND: Spermatogenesis is the process by which germ cells develop into spermatozoa in the testis. Sperm protamines are small, arginine-rich nuclear proteins which replace somatic histones during spermatogenesis, allowing a hypercondensed DNA state that leads to a smaller nucleus and facilitating sperm head formation. In eutherian mammals, the protamine-DNA complex is achieved through a combination of intra- and intermolecular cysteine cross-linking and possibly histidine-cysteine zinc ion binding. Most metatherian sperm protamines lack cysteine but perform the same function. This lack of dicysteine cross-linking has made the mechanism behind metatherian protamines folding unclear. RESULTS: Protamine sequences from UniProt's databases were pulled down and sorted into homologous groups. Multiple sequence alignments were then generated and a gap weighted relative entropy score calculated for each position. For the eutherian alignments, the cysteine containing positions were the most highly conserved. For the metatherian alignment, the tyrosine containing positions were the most highly conserved and corresponded to the cysteine positions in the eutherian alignment. CONCLUSIONS: High conservation indicates likely functionally/structurally important residues at these positions in the metatherian protamines and the correspondence with cysteine positions within the eutherian alignment implies a similarity in function. One possible explanation is that the metatherian protamine structure relies upon dityrosine cross-linking between these highly conserved tyrosines. Also, the human protamine P1 sequence has a tyrosine substitution in a position expecting eutherian dicysteine cross-linking. Similarly, some members of the metatherian Planigales genus contain cysteine substitutions in positions expecting plausible metatherian dityrosine cross-linking. Rare cysteine-tyrosine cross-linking could explain both observations.

Hemorragia intracerebral espontânea: dificuldade diagnóstica entre sangramento neoplásico e hipertensivo / Spontaneous intracerebral hemorrhage: diagnostic difficulties between neoplastic bleeding and hipertensive hemorrhagic stroke

Introdução: A hemorragia intracraniana espontânea (HICE) pode ser a primeira manifestação clínica de um tumor cerebral, cujas características sintomatológicas e tomográficas se assemelham a uma hemorragia típica por hipertensão arterial sistêmica, dificultando e retardando um possível diagnóstico precoce para os casos, sendo a definição dessa dúvida de fundamental importância para uma evolução favorável.Objetivo: Analisar as dificuldades diagnósticas entre hemorragias intracerebrais espontâneas e aquelas decorrentes de lesões secundárias a processos expansivos cerebrais.Métodos: Analisamos uma série de 3694 casos de hemorragia cerebral, entre 1979 e 2011, obtendo 101 casos decorrentes de hemorragia secundária a tumores cerebrais, dos quais em 26 houve dúvidas diagnósticas entre a hemorragia hipertensiva e a transformação hemorrágica neoplásica. Estes casos foram analisados, observando-se suas manifestações clínicas, localização mais frequente do hematoma intracerebral, o estudo anatomopatológico das lesões que sangraram, e a resolução dos casos de acordo com a evolução versus tempo.Resultados: As metástases foram os tumores que mais frequentemente apresentaram sangramento. Os glioblastomas multiformes foram os tumores encefálicos primários mais comumente relacionados a transformação hemorrágica.Conclusão: As hemorragias intratumorais podem ser a manifestação inicial de tumores encefálicos, sendo ela algumas vezes indistinguíveis de AVCh típico (hipertensivo), tanto nas características clínicas quanto na imagem tomográfica, dificultando o diagnóstico. A hemorragia intratumoral ocorre com mais freqüência nas metástases cerebrais do que nos gliomas, Dos tumores cerebrais primários, o glioblastoma multiforme foi a causa mais comum de sangramento.

Introduction: Spontaneous intracranial hemorrhage (SIH)may be the first clinical manifestation of a brain tumor,whose symptoms and CT features may resemble a typicalhypertensive bleeding. This doubt can complicate and delaya possible early diagnosis for those cases. The answer for thisdoubt is of fundamental importance for a favorable outcome.Objectives: The diagnostic difficulties among spontaneousintracerebral hemorrhage and those resulting from secondarylesions of brain’s expansive processes are presented with.Methods: A series of 3694 cases of brain hemorrhagewere analyzed, between 1979 and 2011, in which 101 werehemorrhage secondary to bleeding of brain tumors. In those101 cases, there were twenty-six cases, where a hemorrhagedue to tumour or to hypertension was doubtful. We demonstratethe clinical symptoms, location of intracerebral hematoma,CT and MRI image characteristics and also pathologicalreports, revealing the most commom tumor lesions. The mostfrequent locations of intracranial hemorrhage and resolutionaccording to the particularity of each case were analyzed.Results: Metastases were the most common tumors that oftenbled and glioblastoma multiforme was the most commonbleeding primary brain tumor.Conclusion: Intratumoral hemorrhage may be the initialmanifestation of brain tumors and sometimes they areindistinguishable from typical hypertensive SIH, both inclinical and tomographic imaging, making the diagnosis moredifficult. Intratumoral hemorrhage is more frequent in brainmetastases; in primary tumors, glioblastoma multiforme is thecommoner cause of bleeding. A prompt and correct diagnosisof those lesions are directly linked to the good outcome inthose cases.