The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions

AbstractLigand-induced activation of receptor tyrosine kinases (RTK) results in the initiation of diverse cellular pathways, including proliferation, differentiation and cell migration. The ErbB family of RTKs represents a model for signal diversification through the formation of homo- and heterodimeric receptor complexes. Each dimeric receptor complex will initiate a distinct signaling pathway by recruiting a different set of Src homology 2- (SH2-) containing effector proteins. Further complexity is added due to the existence of an oncogenic receptor that enhances and stabilizes dimerization but has no ligand (ErbB-2), and a receptor that can recruit novel SH-2-containing proteins, but is itself devoid of kinase activity (ErbB-3). The resulting signaling network has important implications for embryonic development and malignant transformation

Near-stasis in the long-term diversification of Mesozoic tetrapods

How did evolution generate the extraordinary diversity of vertebrates on land? Zero species are known prior to ~380 million years ago, and more than 30,000 are present today. An expansionist model suggests this was achieved by large and unbounded increases, leading to substantially greater diversity in the present than at any time in the geological past. This model contrasts starkly with empirical support for constrained diversification in marine animals, suggesting different macroevolutionary processes on land and in the sea. We quantify patterns of vertebrate standing diversity on land during the Mesozoic–early Paleogene interval, applying sample-standardization to a global fossil dataset containing 27,260 occurrences of 4,898 non-marine tetrapod species. Our results show a highly stable pattern of Mesozoic tetrapod diversity at regional and local levels, underpinned by a weakly positive, but near-zero, long-term net diversification rate over 190 million years. Species diversity of non-flying terrestrial tetrapods less than doubled over this interval, despite the origins of exceptionally diverse extant groups within mammals, squamates, amphibians, and dinosaurs. Therefore, although speciose groups of modern tetrapods have Mesozoic origins, rates of Mesozoic diversification inferred from the fossil record are slow compared to those inferred from molecular phylogenies. If high speciation rates did occur in the Mesozoic, then they seem to have been balanced by extinctions among older clades. An apparent 4-fold expansion of species richness after the Cretaceous/Paleogene (K/Pg) boundary deserves further examination in light of potential taxonomic biases, but is consistent with the hypothesis that global environmental disturbances such as mass extinction events can rapidly adjust limits to diversity by restructuring ecosystems, and suggests that the gradualistic evolutionary diversification of tetrapods was punctuated by brief but dramatic episodes of radiation.27 page(s

Paul's use of 'Christ Rhetoric' in 1 Corinthians: a case study from 1 Corinthians 15:1-34

While many scholars have used classical rhetoric for the interpretation of 1 Corinthians, others have proposed alternate methods for the same purpose. The problem with these methods is that they are not based on a closer reading of Paul, rather they are based on different flavors of the rhetorical system and sociological theories. My own approach to this problem is to look at the text of 1 Corinthians with an eye for methodology. A careful analysis of the 1 Corinthian passages yields Paul's rhetorical methods that are different to the classical rhetoric and modern scholars' attempts to find new rhetorical methods. The rhetoric in 1 Corinthians is unique because in every significant issue Paul addresses, he uses a Christ centered response. As such, it calls for a recognition of a Christ centered rhetoric, thus the name Christ Rhetoric. This rhetoric is used often enough in 1 Corinthians to be formalized into a rhetorical/interpretive methodology with its own structure, topoi, and argumentative methods. This resultant methodology is then applied to 1 Corinthians 15:1-34 as a case study

Nemesis Reconsidered

The hypothesis of a companion object (Nemesis) orbiting the Sun was motivated by the claim of a terrestrial extinction periodicity, thought to be mediated by comet showers. The orbit of a distant companion to the Sun is expected to be perturbed by the Galactic tidal field and encounters with passing stars, which will induce variation in the period. We examine the evidence for the previously proposed periodicity, using two modern, greatly improved paleontological datasets of fossil biodiversity. We find that there is a narrow peak at 27 My in the cross-spectrum of extinction intensity time series between these independent datasets. This periodicity extends over a time period nearly twice that for which it was originally noted. An excess of extinction events are associated with this periodicity at 99% confidence. In this sense we confirm the originally noted feature in the time series for extinction. However, we find that it displays extremely regular timing for about 0.5 Gy. The regularity of the timing compared with earlier calculations of orbital perturbation would seem to exclude the Nemesis hypothesis as a causal factor.Comment: 10 pages, 2 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

A neuraminidase from Trypanosoma cruzi removes sialic acid from the surface of mammalian myocardial and endothelial cells

Trypanosoma cruzi causes Chagasic heart disease, a major public health problem in Latin America. The mechanism of interaction of this protozooan parasite with host cells is poorly understood. We recently found that the infective trypomastigote form a T. cruzi exhibits neuraminidase activity and can desialylate mammalian erythrocytes. However, it is not known if T. cruzi can also modify the surfaces of cardiovascular cells that are directly involved in the most important clinical manifestations of this disease. Accordingly, this study determined whether T. cruzi can remove sialic acid from cultured rat myocardial or human vascular endothelial cells. Sialic acid was labeled metabolically with the precursor 3H-N-acetyl-D-mannosamine. Soluble neuraminidase, isolated from intact T. cruzi trypomastigotes, caused significant release of labeled material from myocardial cells (e.g., 2,174 +/- 27 dpm/h vs. spontaneous release of 306 +/- 30 dpm/h, n = 4, P less than 0.001). Chromatographic analysis showed that the bulk of the radioactivity released by T. cruzi neuraminidase was sialic acid. Intact T. cruzi trypomastigotes also released sialic acid from metabolically labeled myocardial cells in a concentration-dependent manner. In contrast, a noninfective form of T. cruzi, the amastigote, did not desialylate these cells. Galactose oxidase labeling demonstrated newly desialylated glycoproteins on the surface of myocardial cells treated with T. cruzi neuraminidase. Desialylation of myocardial cells was confirmed histochemically by the appearance of binding sites for peanut agglutinin, a lectin that binds to complex oligosaccharide moieties after removal of the terminal sialyl residue. T. cruzi neuraminidase also removed sialic acid from adult human saphenous vein endothelial cells, as determined by both histochemical and metabolic labeling studies. Thus, infective forms of T. cruzi can chemically modify the surfaces of myocardial and vascular endothelial cells by desialylation. This alteration may play a role in the initial interaction of this parasite with these important target cells of the host cardiovascular system

PENETRALAN pH AIR KOLAM TANAH GAMBUT UNTUK BUDIDAYA IKAN GURAMI (Osphronemus gouramy)

Penelitian ini dilakukan untuk mengetahui kelangsungan hidup dan pertumbuhan ikan gurami yang dipelihara di kolam dengan penambahan kapur dan tanpa penambahan kapur. Penelitian ini dilaksanakan selama 8 (delapan) minggu dimulai dari bulan Januari sampai Februari 2018 di dua kolam tanah yang terletak di Laboratorium D-III Jurusan Perikanan Fakultas Pertanian Universitas Palangka Raya. Tiga ratus ekor benih ikan gurami digunakan sebagai ikan uji dengan ukuran 3-5 cm. Kolam 1 digunakan untuk menetralkan derajat keasaman (pH) air dengan menggunakan kapur pertanian dengan dosis 0,53 g/liter, sedangkan kolam 2 tanpa perlakuan penetralan atau sebagai kontrol. Penelitian ini diulangi sebanyak 3 kali. Pemberian pakan ikan sebanyak 2 kali selama 2 (dua) bulan pengaatan. Hasil penelitian menunjukkan bahwa tingkat kelangsungan hidup ikan yang dipelihara pada kolam yang diberi penambahan kapur lebih bagus jika di bandingkan dengan ikan yang dipelihara pada kolam tanpa penambahan kapur. Namun, pertumbuhan bobot dan panjang, laju pertumbuhan harian dan rasio konversi pakan lebih baik pada kolam kontrol

Immunization of Rats With Cholinergic Neurons Induces Behavioral Deficits

We have previously shown that sera from patients with Alzheimer's disease (AD) contain a significantly high level of antibodies to the cell bodies (Perikarya; PK) but not to the nerve terminals (synaptosomes) of purely cholinergic neurons from the electric fish Torpedo. In the present study we examined the effect of repeated immunization of rats with either of these antigens for one year. Immunoblot studies revealed that sera of cholinergic PK immunized rats contained a high level of antibodies to cholinergic PK proteins, in particular to a 200 kilodalton protein, to which there are specifically high levels of antibodies in AD. Sera from rats immunized with cholinergic synaptosomes and from control rats contained very low levels of these antibodies. Behavioral studies performed one year after the initial immunization revealed that the cholinergic PK immunized rats were impaired in spatial learning and memory tasks (Morris swim test and T-maze alternation) when compared to control rats and that the synaptosome-immunized rats showed no such deficit. In contrast, the three groups performed similarly in general activity, active avoidance and conditioned emotional response tests. Further experiments revealed that the cholinergic PK immunized rats displayed a significant deficit in short term memory. The association of antibodies to cholinergic neurons with Cognitive deficits in this rat model suggests that such antibodies may be involved in the pathogenesis of AD

The Impact of the Species–Area Relationship on Estimates of Paleodiversity

Estimates of paleodiversity patterns through time have relied on datasets that lump taxonomic occurrences from geographic areas of varying size per interval of time. In essence, such estimates assume that the species–area effect, whereby more species are recorded from larger geographic areas, is negligible for fossil data. We tested this assumption by using the newly developed Miocene Mammal Mapping Project database of western North American fossil mammals and its associated analysis tools to empirically determine the geographic area that contributed to species diversity counts in successive temporal bins. The results indicate that a species–area effect markedly influences counts of fossil species, just as variable spatial sampling influences diversity counts on the modern landscape. Removing this bias suggests some traditionally recognized peaks in paleodiversity are just artifacts of the species–area effect while others stand out as meriting further attention. This discovery means that there is great potential for refining existing time-series estimates of paleodiversity, and for using species–area relationships to more reliably understand the magnitude and timing of such biotically important events as extinction, lineage diversification, and long-term trends in ecological structure

Can we translate vitamin D immunomodulating effect on innate and adaptive immunity to vaccine response?

Vitamin D (VitD), which is well known for its classic role in the maintenance of bone mineral density, has now become increasingly studied for its extra-skeletal roles. It has an important influence on the body's immune system and modulates both innate and adaptive immunity and regulates the inflammatory cascade. In this review our aim was to describe how VitD might influence immune responsiveness and its potential modulating role in vaccine immunogenicity. In the first instance, we consider the literature that may provide molecular and genetic support to the idea that VitD status may be related to innate and/or adaptive immune response with a particular focus on vaccine immunogenicity and then discuss observational studies and controlled trials of VitD supplementation conducted in humans. Finally, we conclude with some knowledge gaps surrounding VitD and vaccine response, and that it is still premature to recommend "booster" of VitD at vaccination time to enhance vaccine response

Ecological interactions disrupted by habitat alteration in the Neotropics

Ecological interactions help determine the distribution of species across landscapes and play crucial roles in ecosystem services such as pollination, seed dispersal, and pest control1. Human disturbances, particularly habitat alteration, have the potential to modify or erase ecological interactions2,3 and so jeopardise the processes they control. While examples of interactions becoming rewired under human influence have been recorded, studies of this process for speciose assemblages at regional to continental scales are uncommon4 and obstructed by logistical difficulties2. The consequences for ecological communities and people are therefore poorly understood. Here we show that human habitat alteration is associated with a decrease in the spatial aggregation of Neotropical bat pairs and bird pairs that share similar dietary requirements. We find that groups of species pairs with similar vs. different diets have positive spatial associations on average, but pairs within dietary guilds have stronger associations than pairs with disparate diets when habitats are relatively intact. Our results suggest that species with similar resource requirements typically coexist in relatively intact natural settings. By contrast, exclusion becomes more common (though not dominant) when habitats are altered. Altered habitats thus fail to support the coexistence of diverse competitive interactions, reversing patterns observed in the wild