Positive Interactions between Desert Granivores: Localized Facilitation of Harvester Ants by Kangaroo Rats

Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis) mounds and rough harvester ant (Pogonomyrmex rugosus) colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m). Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Aβ Mediated Diminution of MTT Reduction—An Artefact of Single Cell Culture?

The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) reduction assay is a frequently used and easily reproducible method to measure beta-amyloid (Aβ) toxicity in different types of single cell culture. To our knowledge, the influence of Aβ on MTT reduction has never been tested in more complex tissue. Initially, we reproduced the disturbed MTT reduction in neuron and astroglia primary cell cultures from rats as well as in the BV2 microglia cell line, utilizing four different Aβ species, namely freshly dissolved Aβ (25-35), fibrillar Aβ (1-40), oligomeric Aβ (1-42) and oligomeric Aβ (1-40). In contrast to the findings in single cell cultures, none of these Aβ species altered MTT reduction in rat organotypic hippocampal slice cultures (OHC). Moreover, application of Aβ to acutely isolated hippocampal slices from adult rats and in vivo intracerebroventricular injection of Aβ also did not influence the MTT reduction in the respective tissue. Failure of Aβ penetration into the tissue cannot explain the differences between single cells and the more complex brain tissue. Thus electrophysiological investigations disclosed an impairment of long-term potentiation (LTP) in the CA1 region of hippocampal slices from rat by application of oligomeric Aβ (1-40), but not by freshly dissolved Aβ (25-35) or fibrillar Aβ (1-40). In conclusion, the experiments revealed a glaring discrepancy between single cell cultures and complex brain tissue regarding the effect of different Aβ species on MTT reduction. Particularly, the differential effect of oligomeric versus other Aβ forms on LTP was not reflected in the MTT reduction assay. This may indicate that the Aβ oligomer effect on synaptic function reflected by LTP impairment precedes changes in formazane formation rate or that cells embedded in a more natural environment in the tissue are less susceptible to damage by Aβ, raising cautions against the consideration of single cell MTT reduction activity as a reliable assay in Alzheimer's drug discovery studies

Meta-analysis of thyroidectomy with ultrasonic dissector versus conventional clamp and tie

<p>Abstract</p> <p>Background</p> <p>We conducted a systematic review to evaluate the role of Ultrasonic dissector (UAS) versus conventional clamp and tie in thyroidectomy.</p> <p>Materials and methods</p> <p>We searched for all published RCT in into electronic databases. To be included in the analysis, the studies had to compare thyroidectomy with UAS versus conventional vessel ligation and tight (conventional technique = CT). The following outcomes were used to compare the total thyroidectomy group with UAS versus CT group: operative duration, operative blood loss, overall drainage volume during the first 24 hours, transiet laryngeal nerve palsy, permanent laryngeal nerve palsy, transiet hypocalcaemia and permanent hypocalcaemia.</p> <p>Results</p> <p>There are currently 7 RCT on this issue to compare thyroidectomy with UAS versus CT. From the analysis of these studies it was possible to confront 608 cases: 303 undergoing to thyroidectomy with UAS versus 305 that were treated with CT. Actually, it was shown a relevant advantage of cost-effectiveness in patients treated with UAS; there is a statistically significant reduction of the operative duration (weighted mean difference [WMD], -18.74 minutes; 95% confidence interval [CI], (-26.97 to -10.52 minutes) (P = 0.00001), intraoperative blood loss (WMD, -60.10 mL; 95% CI, -117.04 to 3.16 mL) (P = 0.04) and overall drainage volume (WMD, -35.30 mL; 95% CI, -49.24 to 21.36 mL) (P = 0.00001) in the patients underwent thyroidectomy with UAS. Although the analysis showed that the patients who were treated with USA presented more favourable results in incidence of post-operative complications (transient laryngeal nerve palsy: P = 0.11; permanent laryngeal nerve palsy: not estimable; transient hypocalcaemia: P = 0.24; permanent hypocalcaemia: P = 0.45), these data didn't present statistical relevance.</p> <p>Conclusion</p> <p>This meta-analysis shown a relevant advantage only in terms of cost-effectiveness in patients treated with UAS; it is subsequent to statistically significant reduction of operation duration, intraoperative blood loss and of overall drainage volume during the first 24 hours. Although the analysis showed that the patients who were treated with UAS presented more favourable results in incidence of post-operative complications (transiet laryngeal nerve palsy; transiet hypocalcaemia and permanent hypocalcaemia), these data didn't present statistical relevance.</p

Rapid Transcriptional Pulsing Dynamics of High Expressing Retroviral Transgenes in Embryonic Stem Cells

Single cell imaging studies suggest that transcription is not continuous and occurs as discrete pulses of gene activity. To study mechanisms by which retroviral transgenes can transcribe to high levels, we used the MS2 system to visualize transcriptional dynamics of high expressing proviral integration sites in embryonic stem (ES) cells. We established two ES cell lines each bearing a single copy, self-inactivating retroviral vector with a strong ubiquitous human EF1α gene promoter directing expression of mRFP fused to an MS2-stem-loop array. Transfection of MS2-EGFP generated EGFP focal dots bound to the mRFP-MS2 stem loop mRNA. These transcription foci colocalized with the transgene integration site detected by immunoFISH. Live tracking of single cells for 20 minutes detected EGFP focal dots that displayed frequent and rapid fluctuations in transcription over periods as short as 25 seconds. Similarly rapid fluctuations were detected from focal doublet signals that colocalized with replicated proviral integration sites by immunoFISH, consistent with transcriptional pulses from sister chromatids. We concluded that retroviral transgenes experience rapid transcriptional pulses in clonal ES cell lines that exhibit high level expression. These events are directed by a constitutive housekeeping gene promoter and may provide precedence for rapid transcriptional pulsing at endogenous genes in mammalian stem cells

Patients' and urologists' preferences for prostate cancer treatment: A discrete choice experiment

__Abstract__ Background: Patients' preferences are important for shared decision making. Therefore, we investigated patients' and urologists' preferences for treatment alternatives for early prostate cancer (PC). Methods: A discrete choice experiment was conducted among 150 patients who were waiting for their biopsy results, and 150 urologists. Regression analysis was used to determine patients' and urologists' stated preferences using scenarios based on PC treatment modality (radiotherapy, surgery, and active surveillance (AS)), and risks of urinary incontinence and erectile dysfunction.Results:The response rate was 110 out of 150 (73%) for patients and 50 out of 150 (33%) for urologists. Risk of urinary incontinence was an important determinant of both patients' and urologists' stated preferences for PC treatment (P<0.05). Treatment modality also influenced patients' stated preferences (P<0.05), whereas the risk of erectile dysfunction due to radiotherapy was mainly important to urologists (P<0.05). Both patients and urologists preferred AS to radical treatment, with the exception of patients with anxious/depressed feelings who preferred radical treatment to AS. Conclusion: Although patients and urologists generally may prefer similar treatments for PC, they showed different trade-offs between various specific treatment aspects. This implies that urologists need to be aware of potential differences compared with the patient's perspective on treatment decisions in shared decision making on PC treatment

Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 -251 polymorphisms in the risk for the development of distal gastric cancer

<p>Abstract</p> <p>Background</p> <p>The intensity of the inflammation induced by <it>Helicobacter pylori </it>colonization is associated with the development of distal gastric cancer (GC). The host response to <it>H</it>. <it>pylori </it>has been related to genetic polymorphisms that influence both innate and adaptive immune responses.</p> <p>Our aim was to investigate whether the presence of the <it>TLR4 Asp299Gly</it>, <it>TLR4 Thr399Ile </it>and <it>IL-8-251 </it>A/T polymorphisms had any influence in the development of distal GC in a Mexican population.</p> <p>Methods</p> <p>We studied 337 patients that were divided in two groups: 78 patients with histologically confirmed distal GC and 259 non-cancer controls. The presence of <it>H. pylori </it>in the control population was defined by positive results of at least two of four diagnostic tests: serology, histology, rapid urease test and culture. Human DNA was purified and genotyped for <it>TLR4 Asp299Gly </it>polymorphism by pyrosequencing, for <it>TLR4 Thr399Ile </it>by PCR-RFLP and for <it>IL8-251 </it>by the amplification refractory mutation system (ARMS)-PCR.</p> <p>Results</p> <p>The non-cancer control group was found to be in Hardy-Weinberg equilibrium at the polymorphic loci studied (chi-square _H-W= 0.58 for <it>IL8-251</it>, 0.42 for <it>TLR4 Asp299Gly </it>and 0.17 for <it>TLR4 Thr399Ile</it>). The frequencies of mutated alleles (homozygous plus heterozygous) were compared between cases and controls. We found no significant difference for <it>TLR4- Asp299Gly </it>[the 7.7% of distal GC patients and 7.7 % non-cancer controls (p = 0.82)] and for <it>TLR4 Thr399Ile </it>[the 1.3% of GC patients and the 5% of the control population (p = 0.2)]. In contrast, for <it>IL-8-251 </it>A/T, 80.77% of the GC patients and 66.4% in the control group age and gender matched had at least one copy of mutated allele (OR = 2.12, 95% CI = 1.1–4.2) (p = 0.023).</p> <p>Conclusion</p> <p>This study showed that the <it>IL8-251*A </it>allele could be related to the development of distal gastric cancer in this Mexican population.</p

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution

Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

<p>Abstract</p> <p>Background</p> <p>Toll like receptors (TLR) play the central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in the TLR1, TLR2 and TLR4 genes may change the ability to recognize PAMPs and cause altered responsiveness to the bacterial pathogens.</p> <p>Results</p> <p>The study presents association between TLR gene mutations and increased susceptibility to <it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP) infection. Novel mutations in TLR genes (TLR1- Ser150Gly and Val220Met; TLR2 – Phe670Leu) were statistically correlated with the hindrance in recognition of MAP legends. This correlation was confirmed subsequently by measuring the expression levels of cytokines (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the mutant and wild type moDCs (mocyte derived dendritic cells) after challenge with MAP cell lysate or LPS. Further <it>in silico </it>analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR (leucine rich repeat) motifs.</p> <p>Conclusion</p> <p>The most critical positions that may alter the pathogen recognition ability of TLR were: the 9^thamino acid position in LRR motif (TLR1–LRR10) and 4^thresidue downstream to LRR domain (exta-LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection.</p