Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus

Faint-source-star planetary microlensing: the discovery of the cold gas-giant planet OGLE-2014-BLG-0676Lb

We report the discovery of a planet – OGLE-2014-BLG-0676Lb– via gravitational microlensing. Observations for the lensing event were made by the following groups: Microlensing Observations in Astrophysics; Optical Gravitational Lensing Experiment; Wise Observatory; RoboNET/Las Cumbres Observatory Global Telescope; Microlensing Network for the Detection of Small Terrestrial Exoplanets; and μ-FUN. All analyses of the light-curve data favour a lens system comprising a planetary mass orbiting a host star. The most-favoured binary lens model has a mass ratio between the two lens masses of (4.78 ± 0.13) × 10−3. Subject to some important assumptions, a Bayesian probability density analysis suggests the lens system comprises a 3.09+1.02 −1.12 MJ planet orbiting a 0.62+0.20 −0.22 M host star at a deprojected orbital separation of 4.40+2.16 −1.46 au. The distance to the lens system is 2.22+0.96 −0.83 kpc. Planet OGLE- 2014-BLG-0676Lb provides additional data to the growing number of cool planets discovered using gravitational microlensing against which planetary formation theories may be tested. Most of the light in the baseline of this event is expected to come from the lens and thus high-resolution imaging observations could confirm our planetary model interpretation

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year ( with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months ( patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 mug of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies

Gene diversity in grevillea populations introduced in Brazil and its implication on management of genetic resources.

A variabilidade isoenzimática para seis populações de Grevillea robusta, oriundas de um teste de procedências/progenies, implantado no delineamento em blocos casualizados com 5 plantas por parcela, no Sul do Brasil, é descrita. A estrutura genética da população foi analisada utilizando-se marcadores bioquímicos, aos 5 anos de idade, especificamente para os locos MDH-3, PGM-2, DIA-2, PO-1, PO-2, SOD-1, e SKDH-1. As procedências do norte de ocorrência natural (Rathdowney e Woodenbong) apresentaram divergência genética superior, em relação à média das progênies, considerando o número de alelos por locus, (Ap), a riqueza alélica (Rs), a diversidade genética de Nei (H), e o coeficiente de endogamia (f). A endogamia foi detectada em diversos graus. A testemunha comercial apresentou o maior coeficiente de endogamia, (f = 0,4448), comparativamente à média das procedências (f = 0,2306), possivelmente devido à insuficiente amostragem populacional na região de origem (Austrália). Apesar de sua ocorrência natural restrita, observou-se correlação positiva entre divergência genética e distância geográfica entre as populações originais. A distância genética e análise de cluster, baseada no modelo bayesiano, mostrou três grupos de procedências distintos: 1) Rathdowney- QLD e Woodenbong-QLD; 2) Paddy?s Flat-NSW; e 3) Mann River-NSW, Boyd River-NSW e a testemunha comercial (material utilizado no Brasil). O agrupamento da testemunha com as procedências Mann River-NSW e Boyd River-NSW sugere um maior potencial das procedências do norte para o melhoramento genético visando à produção de madeira no Brasil, devido a sua elevada diversidade genética e baixo coeficiente de endogamia

Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.

High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome