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Abstract During cell division, the microtubule cytoskeleton undergoes dramatic cell cycle-driven reorganizations of its architecture. Coordinated by changes in the phosphorylation patterns of a multitude of microtubule associated proteins, the mitotic spindle first self-assembles to capture the chromosomes and then reorganizes in anaphase as the chromosomes are segregated. A key protein for this reorganization is PRC1 which is differentially phosphorylated by the mitotic kinases CDK1 and PLK1. How the phosphorylation state of PRC1 orchestrates spindle reorganization is not understood mechanistically. Here, we reconstitute in vitro the transition between metaphase and anaphase-like microtubule architectures triggered by the changes in PRC1 phosphorylation. We find that whereas PLK1 regulates its own recruitment by PRC1, CDK1 controls the affinity of PRC1 for antiparallel microtubule binding. Dephosphorylation of CDK1-phosphorylated PRC1 is required and sufficient to trigger the reorganization of a minimal anaphase midzone in the presence of the midzone length controlling kinesin KIF4A. These results demonstrate how phosphorylation-controlled affinity changes regulate the architecture of active microtubule networks, providing new insight into the mechanistic underpinnings of the cell cycle-driven reorganization of the central spindle during mitosis.

The temporary or permanent chemical modification of biomolecules is a crucial aspect in the physiology of all living species. However, while some modules are well characterised also in insects, others did not receive the same attention. This holds true for sulfo-conjugation that is catalysed by cytosolic sulfotransferases (SULT), a central component of the metabolism of endogenous low molecular weight molecules and xenobiotics. In particular, limited information is available about the functional roles of the mosquito predicted enzymes annotated as SULTs in genomic databases. The herein described research is the first example of a biochemical and structural study of a SULT of a mosquito species, in general, and of the malaria vector Anopheles gambiae in particular. We confirmed that the AGAP001425 transcript displays a peculiar expression pattern that is suggestive of a possible involvement in modulating the mosquito reproductive tissues physiology, a fact that could raise attention on the enzyme as a potential target for insect-containment strategies. The crystal structures of the enzyme in alternative ligand-bound states revealed elements distinguishing AgSULT-001425 from other characterized SULTs, including a peculiar conformational plasticity of a discrete region that shields the catalytic cleft and that could play a main role in the dynamics of the reaction and in the substrate selectivity of the enzyme. Along with further in vitro biochemical studies, our structural investigations could provide a framework for the discovery of small-molecule inhibitors to assess the effect of interfering with AgSULT-001425-mediated catalysis at the organismal level.

Occult breast cancer (OBC) is a rare entity and, to date, still represents a diagnostic and therapeutic challenge. OBC is often diagnosed as metastatic dissemination without a recognized primary; this delay in diagnosis and the known increased tumor aggressiveness can condition treatment choices and patients’ outcomes. In this report, we describe three atypical presentations of breast cancer. The first corresponds to an OBC with axillary lymphadenopathy which is the most frequent finding in the literature. Another one describes diffuse bone metastases from breast tumors diagnosed through bone biopsy without any primitive breast lesion with all applied radiological imaging. The third one is instead an overt breast cancer with a pathological profile of a low aggressive tumor showing bulky lung involvement. The first OBC description dated back to Halstead's description in 1907 and represents a little-explored niche which however should be nowadays studied to define biological determinants probably influencing a different presentation and behavior

Coleções de objetos para fins educacionais recebem hoje em dia atenção especial com o desenvolvimento dos estudos sobre recepção da Antiguidade clássica. De fato, essas coleções nos permitem estudar a evolução no tempo do interesse despertado pela Antiguidade, bem como a história de nossas disciplinas e seus métodos pedagógicos. Neste artigo, propomos analisar a forma como moldagens de gesso, modelos e instrumentos de estudo da Antiguidade foram usados com o propósito de ensinar história da arte greco-romana, com uma atenção particular a algumas tradições nacionais. A reprodução por intermédio de moldagens não é apenas um substituto de um original, é também uma obra de arte, num diálogo entre a obra original, sua interpretação e sua cópia. Em suma, moldagens são obras de arte complexas, ilustrando as idas e vindas entre arte e arqueologia.

The centromere, a chromosome locus defined by the histone H3-like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G1 phase of the cell cycle to compensate for its dilution after DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside of early G1. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G1, but the molecular details of this process are still unknown. We reveal here a phosphorylation network that recruits PLK1 to the deposition machinery to control a conformational switch required for licensing the CENP-A deposition reaction. Our findings clarify how PLK1 contributes to the epigenetic maintenance of centromeres. [ABSTRACT FROM AUTHOR]