Diet of the South African large-spotted genet Genetta tigrina (Carnivora, Viverridae) in a coastal dune forest

We studied seasonal variations in the diet of the large-spotted genet Genetta tigrina Schreber, 1776 in the coastal dune forest of the Dwesa Nature Reserve, Eastern Cape Province, South Africa. The food items with the highest relative percentage occurrence were Coleoptera, Orthoptera and Mammalia. However, by volume they ate mostly grass then followed by Coleoptera and Orthoptera. Main prey items originated from the litter layer or low lying bushes, such as arachnids, insects, myriapods, and most mammals. The latter included ten rodent (main staple: Dendromus sp.), two golden mole and two shrew species, from 10–100 g mass. They were represented dependent on species density, but switching between seasons and habitats occupied. Birds appeared under-represented in the diet for a semi-arboreal carnivore, although this correlates with data from other studies. Remains of birds in the diet, however, peaked during winter and spring probably as a result of the main nesting period in spring. There were some variation in diet between habitats (riparian, forest and beach) and seasons. Our results show the South African large-spotted genet to have an opportunistic, generalist diet.NERC, Eastern Cape Parks, NRF, CI

Fungsi Sosiologis Undang-undang Dasar Negara Republik Indonesia Tahun 1945 Dalam Memenuhi Hak-hak Masyarakat

Constitution is a binding social contract between government and citizen. Their relationships figure the rights of the society. These rightsbecome the tool of society to participate in making government policy, to control the governmentand to avoid the practice of absolutpower.Therefore, the 1945 Indonesian Constitution regulates the norms of rights of society. The functions of the rights are to up hold society justice as well as to create society welfare. The regulation of rights of society in Indonesian Constitution indicates itssociological function.It accommodates the right of society in its relationship between government and citizen

ABCC4/MRP4 contributes to the aggressiveness of Myc-associated epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters are known for roles in both drug resistance and cancer biology and are also highly targetable. Here we have investigated the association of ABCC4/MRP4 expression to clinical outcome and its biological function in endometrioid and serous tumors, common histological subtypes of EOC. We found high expression of ABCC4/MRP4, previously shown to be directly regulated by c-Myc/N-Myc, was associated with poor prognosis in endometrioid EOC (P =.001) as well as in a subset of serous EOC with a “high-MYCN” profile (C5/proliferative; P =.019). Transient siRNA-mediated suppression of MRP4 in EOC cells led to reduced growth, migration and invasion, with the effects being most pronounced in endometrioid and C5-like serous cells compared to non-C5 serous EOC cells. Sustained knockdown of MRP4 also sensitized endometrioid cells to MRP4 substrate drugs. Furthermore, suppression of MRP4 decreased the growth of patient-derived EOC cells in vivo. Together, our findings provide the first evidence that MRP4 plays an important role in the biology of Myc-associated ovarian tumors and highlight this transporter as a potential therapeutic target for EOC

Suppression of ABCE1-mediated mRNA translation limits N-MYC-driven cancer progression

The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% of high-risk patients surviving past 5 years. However, decades of attempts of direct inhibition of N-MYC or its paralogues has led to the conclusion that this protein is “undruggable.” Therefore, targeting pathways upregulated by N-MYC signaling presents an alternative therapeutic approach. Here, we show that MYCN-amplified neuroblastomas are characterized by elevated rates of protein synthesis and that high expression of ABCE1, a translation factor directly upregulated by N-MYC, is itself a strong predictor of poor clinical outcome. Despite the potent ability of N-MYC in heightening protein synthesis and malignant characteristics in cancer cells, suppression of ABCE1 alone selectively negated this effect, returning the rate of translation to baseline levels and significantly reducing the growth, motility, and invasiveness of MYCN-amplified neuroblastoma cells and patient-derived xenograft tumors in vivo. The growth of nonmalignant cells or MYCN-nonamplified neuroblastoma cells remained unaffected by reduced ABCE1, supporting a therapeutic window associated with targeting ABCE1. Neuroblastoma cells with c-MYC overexpression also required ABCE1 to maintain cell proliferation and translation. Taken together, ABCE1-mediated translation constitutes a critical process in the progression of N-MYC-driven and c-MYC-driven cancers that warrants investigations into methods of its therapeutic inhibition

Systematic In Vitro Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged Leukemia

Patients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics. The aim of this study was to identify novel candidate compounds that selectively target KMT2A-rearranged (KMT2A-r) leukemia cells. A library containing 3707 approved drugs and pharmacologically active compounds was screened for differential activity against KMT2A-r leukemia cell lines versus KMT2A-wild type (KMT2A-wt) leukemia cell lines, solid tumor cells and non-malignant cells by cell-based viability assays. The screen yielded SID7969543, an inhibitor of transcription factor Nuclear Receptor Subfamily 5 Group A Member 1 (NR5A1), that limited the viability of 7 out of 11 KMT2A-r leukemia cell lines including 5 out of 7 lines derived from infants, without affecting KMT2A-wt leukemia cells, solid cancer lines, non-malignant cell lines, or peripheral blood mononuclear cells from healthy controls. The compound also significantly inhibited growth of leukemia cell lines with a CALM-AF10 translocation, which defines a highly aggressive leukemia subtype that shares common underlying leukemogenic mechanisms with KMT2A-r leukemia. SID7969543 decreased KMT2A-r leukemia cell viability by inducing caspase-dependent apoptosis within hours of treatment and demonstrated synergy with established chemotherapeutics used in the treatment of high-risk leukemia. Thus, SID7969543 represents a novel candidate agent with selective activity against CALM-AF10 translocated and KMT2A-r leukemias that warrants further investigation

Ages for exoplanet host stars

Age is an important characteristic of a planetary system, but also one that is difficult to determine. Assuming that the host star and the planets are formed at the same time, the challenge is to determine the stellar age. Asteroseismology provides precise age determination, but in many cases the required detailed pulsation observations are not available. Here we concentrate on other techniques, which may have broader applicability but also serious limitations. Further development of this area requires improvements in our understanding of the evolution of stars and their age-dependent characteristics, combined with observations that allow reliable calibration of the various techniques.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018

The Combination of Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Delays KMT2A-Rearranged Leukemia Progression

Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome. Driven by the unmet need to develop better therapies for KMT2A-rearranged leukemia, we previously discovered that the novel anti-cancer agent, curaxin CBL0137, induces decondensation of chromatin in cancer cells, delays leukemia progression and potentiates standard of care chemotherapies in preclinical KMT2A-rearranged leukemia models. Based on the promising potential of histone deacetylase (HDAC) inhibitors as targeted anti-cancer agents for KMT2A-rearranged leukemia and the fact that HDAC inhibitors also decondense chromatin via an alternate mechanism, we investigated whether CBL0137 could potentiate the efficacy of the HDAC inhibitor panobinostat in KMT2A-rearranged leukemia models. The combination of CBL0137 and panobinostat rapidly killed KMT2A-rearranged leukemia cells by apoptosis and significantly delayed leukemia progression and extended survival in an aggressive model of MLL-AF9 (KMT2A:MLLT3) driven murine acute myeloid leukemia. The drug combination also exerted a strong anti-leukemia response in a rapidly progressing xenograft model derived from an infant with KMT2A-rearranged acute lymphoblastic leukemia, significantly extending survival compared to either monotherapy. The therapeutic enhancement between CBL0137 and panobinostat in KMT2A-r leukemia cells does not appear to be mediated through cooperative effects of the drugs on KMT2A rearrangement-associated histone modifications. Our data has identified the CBL0137/panobinostat combination as a potential novel targeted therapeutic approach to improve outcome for KMT2A-rearranged leukemia

Translocations as Experiments in the Ecological Resilience of an Asocial Mega-Herbivore

Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981–2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world

Fanconi anaemia with bilateral diffuse pulmonary arterio venous fistulae: a case report

<p>Abstract</p> <p>Background</p> <p>We report a patient with cytogenetically confirmed Fanconi anaemia with associated diffuse bilateral pulmonary arterio-venous fistulae. This is only the second reported case of diffuse pulmonary arterio-venous fistulae with Fanconi anaemia.</p> <p>Case Presentation</p> <p>A 16 year old Sri Lankan boy, with a cytogenetically confirmed Fanconi anaemia was admitted to University Medical Unit, National Hospital of Sri Lanka for further assessment and treatment. Both central and peripheral cyanosis plus clubbing were noted on examination. The peripheral saturation was persistently low on room air and did not improve with supplementary Oxygen. Contrast echocardiography failed to demonstrate an intra cardiac shunt but showed early crossover of contrast, suggesting the possibility of pulmonary arterio-venous fistulae. Computed tomography pulmonary angiogram was inconclusive. Subsequent right heart catheterisation revealed bilateral diffuse arterio-venous fistulae not amenable for device closure or surgical intervention.</p> <p>Conclusion</p> <p>To our knowledge, this is the second reported patient with diffuse pulmonary arterio-venous fistulae associated with Fanconi anaemia. We report this case to create awareness among clinicians regarding this elusive association. We recommend screening patients with Fanconi anaemia using contrast echocardiography at the time of assessment with transthoracic echocardiogram. Though universal screening may be impossible given the cost constraints, such screening should at least be performed in patients with clinical evidence of desaturation or when a therapeutic option such as haematopoietic stem cell transplantation is considered. Treatment of pulmonary arteriovenous fistulae would improve patient outcome as desaturation by shunting worsens the anaemic symptoms by reducing the oxygen carrying capacity of blood.</p