The relation between cell proliferation and adenylate cyclase activity in grafts of 3-methylcholanthrene induced mouse uterine cervical tumors

Summary In transplanted uterine cervical tumors, induced by 3-methylcholanthrene, a significant negative correlation was obtained between adenylate cyclase activity and cell proliferation.     

On glioblastoma and the search for a cure: where do we stand?

Although brain tumours have been documented and recorded since the nineteenth century, 2016 marked 90 years since Percival Bailey and Harvey Cushing coined the term “glioblastoma multiforme”. Since that time, although extensive developments in diagnosis and treatment have been made, relatively little improvement on prognosis has been achieved. The resilience of GBM thus makes treating this tumour one of the biggest challenges currently faced by neuro-oncology. Aggressive and robust development, coupled with difficulties of complete resection, drug delivery and therapeutic resistance to treatment are some of the main issues that this nemesis presents today. Current treatments are far from satisfactory with poor prognosis, and focus on palliative management rather than curative intervention. However, therapeutic research leading to developments in novel treatment stratagems show promise in combating this disease. Here we present a review on GBM, looking at the history and advances which have shaped neurosurgery over the last century that cumulate to the present day management of GBM, while also exploring future perspectives in treatment options that could lead to new treatments on the road to a cure.     

Opposing effects on the cell cycle of T lymphocytes by Fbxo7 via Cdk6 and p27

G₁ phase cell cycle proteins, such as cyclin-dependent kinase 6 (Cdk6) and its activating partners, the D-type cyclins, are important regulators of T-cell development and function. An F-box protein, called F-box only protein 7 (Fbxo7), acts as a cell cycle regulator by enhancing cyclin D-Cdk6 complex formation and stabilising levels of p27, a cyclin-dependent kinase inhibitor. We generated a murine model of reduced Fbxo7 expression to test its physiological role in multiple tissues and found that these mice displayed a pronounced thymic hypoplasia. Further analysis revealed that Fbxo7 differentially affected proliferation and apoptosis of thymocytes at various stages of differentiation in the thymus and also mature T-cell function and proliferation in the periphery. Paradoxically, Fbxo7-deficient immature thymocytes failed to undergo expansion in the thymus due to a lack of Cdk6 activity, while mature T cells showed enhanced proliferative capacity upon T-cell receptor engagement due to reduced p27 levels. Our studies reveal differential cell cycle regulation by Fbxo7 at different stages in T-cell development.     

Monocyte participation in connective tissue repair

Zusammenfassung Monocyten des strömenden Blutes könnenin vitro die morphologischen und funktionellen (Hydroxyprolinbildung) Kriterien von Fibrocyten erwerben. Die quantitative Bedeutung dieses Phänomens für den reparativen Bindegewebsaufbau wurde mit folgender Versuchsanordnung geprüft: Vergleichbare Inokulate von Monocyten (enthalten in der Leucocytenhaut des zentrifugierten Blutes) und von Fibrocyten (aus subcutanem Bindegewebe) von Kaninchen verschiedenen Geschlechts, wurden in Millipore-Kammern eingeschlossen und für 14–21 Tage in das Abdomen eines Kaninchens implantiert. Die Auszählung des Sex-Chromatins in den fibrocytären Kernen am Ende der Züchtungsperiode ergibt, dass ca. 50% monocytären Ursprunges sind. Es wird gefolgert, dass dieses Phänomen bei der eigentlichen Wundheilung noch bedeutungsvoller sein dürfte, da der Zustrom teilungsfähiger Monocyten in einem Wundgebiet kontinuierlich vor sich geht und nicht auf ein initiales Inokulum beschränkt ist.     

Heritable changeability: Epimutation and the legacy of negative definition in epigenetic concepts

Epigenetic concepts are fundamentally shaped by a legacy of negative definition, often understood by what they are not. Yet the function and implication of negative definition for scientific discourse has thus far received scant attention. Using the term epimutation as exemplar, we analyze the paradoxical like-but-unlike structure of a term that must simultaneously connect with but depart from genetic concepts. We assess the historical forces structuring the use of epimutation and like terms such as paramutation. This analysis highlights the positive characteristics defining epimutation: the regularity, oxymoronic temporality, and materiality of stable processes. Integrating historical work, ethnographic observation, and insights from philosophical practice-oriented conceptual analysis, we detail the distinctive epistemic goals the epimutation concept fulfils in medicine, plant biology and toxicology. Epimutation and allied epigenetic terms have succeeded by being mutation-like and recognizable, yet have failed to consolidate for exactly the same reason: they are tied simultaneously by likeness and opposition to nouns that describe things that are assumed to persist unchanged over space and time. Moreover, negative definition casts the genetic-epigenetic relationship as an either/or binary, overshadowing continuities and connections. This analysis is intended to assist practitioners and observers of genetics and epigenetics in recognizing and moving beyond the conceptual legacies of negative definition.