The potential of discs from a "mean Green function"

By using various properties of the complete elliptic integrals, we have derived an alternative expression for the gravitational potential of axially symmetric bodies, which is free of singular kernel in contrast with the classical form. This is mainly a radial integral of the local surface density weighted by a regular "mean Green function" which depends explicitly on the body's vertical thickness. Rigorously, this result stands for a wide variety of configurations, as soon as the density structure is vertically homogeneous. Nevertheless, the sensitivity to vertical stratification | the Gaussian profile has been considered | appears weak provided that the surface density is conserved. For bodies with small aspect ratio (i.e. geometrically thin discs), a first-order Taylor expansion furnishes an excellent approximation for this mean Green function, the absolute error being of the fourth order in the aspect ratio. This formula is therefore well suited to studying the structure of self-gravitating discs and rings in the spirit of the "standard model of thin discs" where the vertical structure is often ignored, but it remains accurate for discs and tori of finite thickness. This approximation which perfectly saves the properties of Newton's law everywhere (in particular at large separations), is also very useful for dynamical studies where the body is just a source of gravity acting on external test particles.Comment: Accepted for publication in MNRAS, 11 page

Functional Analysis of Conserved Non-Coding Regions Around the Short Stature hox Gene (shox) in Whole Zebrafish Embryos

Background: Mutations in the SHOX gene are responsible for Leri-Weill Dyschondrosteosis, a disorder characterised by mesomelic limb shortening. Recent investigations into regulatory elements surrounding SHOX have shown that deletions of conserved non-coding elements (CNEs) downstream of the SHOX gene produce a phenotype indistinguishable from Leri-Weill Dyschondrosteosis. As this gene is not found in rodents, we used zebrafish as a model to characterise the expression pattern of the shox gene across the whole embryo and characterise the enhancer domains of different CNEs associated with this gene. Methodology/Principal Findings: Expression of the shox gene in zebrafish was identified using in situ hybridization, with embryos showing expression in the blood, putative heart, hatching gland, brain pharyngeal arch, olfactory epithelium, and fin bud apical ectodermal ridge. By identifying sequences showing 65% identity over at least 40 nucleotides between Fugu, human, dog and opossum we uncovered 35 CNEs around the shox gene. These CNEs were compared with CNEs previously discovered by Sabherwal et al. ,resulting in the identification of smaller more deeply conserved sub-sequence. Sabherwal et al.’s CNEs were assayed for regulatory function in whole zebrafish embryos resulting in the identification of additional tissues under the regulatory control of these CNEs. Conclusion/Significance: Our results using whole zebrafish embryos have provided a more comprehensive picture of the expression pattern of the shox gene, and a better understanding of its regulation via deeply conserved noncoding elements. In particular, we identify additional tissues under the regulatory control of previously identified SHOX CNEs. We also demonstrate the importance of these CNEs in evolution by identifying duplicated shox CNEs and more deeply conserved sub-sequences within already identified CNEs

Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level

gRASping the redox lever to modulate cancer cell fate signaling

RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers

Vacuum correlations at geodesic distance in quantum gravity

The vacuum correlations of the gravitational field are highly non-trivial to be defined and computed, as soon as their arguments and indices do not belong to a background but become dynamical quantities. Their knowledge is essential however in order to understand some physical properties of quantum gravity, like virtual excitations and the possibility of a continuum limit for lattice theory. In this review the most recent perturbative and non-perturbative advances in this field are presented. (To appear on Riv. Nuovo Cim.)Comment: report U.T.F. 332, July 94. Plain TeX, 67 pp. (+ 1 table and 7 figures, available from the author

Hormones, muscles and oncological outcome in men with rectal cancer

Paper I. The aim was to elucidate if testosterone (T) dose-dependently increase muscle size in abdomen and pelvis, analogous to the known anabolic influence on appendicular muscles. Participants were young (age 18-50) healthy men participating in the 5a-reductase trail, a double blinded RCT. Endogenous T production was supressed and replaced with four dosages (50, 125, 300, or 600 mg) of T enanthate. Magnetic Resonance Imaging scans from baseline and end of study was used to analyse change in muscle areas of the lower trunk and pelvis. The estimated change (95% CI) of muscle area increase per 100 mg of T enanthate dosage increase was 0.622 cm2 (0.394, 0.850) for psoas; 1.789 cm2 (1.317, 2.261) for paraspinal muscles; 2.530 cm2 (1.627, 3.434) for total abdominal muscles; 0.455 cm2 (0.233, 0.678) for obturator internus; 0.082 cm2 (0.003, 0.045) for ischiocavernosus. Areas were also associated on-treatment T and free T levels. In conclusion, the abdominal and pelvic muscle are responsive to T administration, opening up for future studies regarding T treatment in frail men with risk for falls and men with pelvic dysfunction. Paper II. Preoperative radiotherapy (RT) is used in treatment of rectal cancer (RC) to enhance local control. Acute testicular failure with risk for permanent damage to T production is a less known adverse effect of RT. The aim was to elucidate long-term effects on T production, and the association of elevated luteinizing hormone (LH) and cancer recurrence. This was a longitudinal prospective cohort study including men with rectal- or prostate cancer stage I-III. Exposure was RT, quantified by mean cumulative testicular dose (TD). Testicular function was assessed by sampling of T, LH and follicle stimulating hormone (FSH) at baseline and at follow-ups after one and two years. Exposed men were additionally sampled preoperatively. Within two years after surgery, T levels recovered, but LH and FSH levels were significantly higher in exposed. Changes in LH and FSH were related to TD. Elevated LH one year after surgery inferred an incidence rate ratio for cancer recurrence in five years of 3·19 (95% C.I.: 0·97-11.2, mid-p=0·036). Paper III. The aim was to analyse the impact of RT induced primary testicular failure on severe postoperative adverse events (AE, Clavien-Dindo grade 3+) in men treated for RC. 104 men were included from the previous cohort study. T and LH were sampled at baseline and after RT. The association between of primary testicular failure and severe postoperative AE was analysed using longitudinal regression. 25% had severe postoperative AE (AE+). Baseline data did not differ significantly between groups. The AE+ group had comparably higher LH/T-ratio after RT. 0.603 (0.2-2.5) vs 0.452 (0.127-5.926, p=0.035). The longitudinal regression analysis found that preoperative change in T (OR 0.844, 95% CI 0.720-0.990, p=0.034), LH/T-ratio (OR 2.020, 95% CI 1.010-4.039, p=0.047) and low T (<8 nmol/L, OR 2.605, 95 CI 0.951-7.139, p=0.063) were associated to severe postoperative AE. Preoperative RT induced decline in T seems to be a risk factor for severe postoperative AE in men with RC. Paper IV. Sarcopenic signs have been related to worse cancer specific survival and the skeletal muscles in men are sensitive to T. The effect of RT induced testicular failure may therefore be of importance in men treated for RC. Based on the cohort study in Paper II, 102 men with RC were included. Using CT or MRI scans from routine examinations at baseline and one year after surgery, skeletal muscle (SM) area at 3rd lumbar vertebra was measured. Testicular function was evaluated by measurement of serum T and LH. The association between change in T (and calculated free T) and SM as well as systemic cancer recurrence and SM were analyzed. Change in free T level is associated with change in psoas major area (p=0.005) and abdominal muscle area (p<0.001). Systemic cancer recurrence was associated with changes in total SM area (-5.96 (-10.7 - -1.24) cm2, p=0.013). In conclusion, Abdominal and pelvic muscles are as androgen sensitive as appendicular muscles, and impaired testicular endocrine function due to RT impacts muscle area. Preoperative decrease in T increase risk of severe postoperative AE. Elevated LH and decreased muscle area are associated with systemic cancer disease

Human-aided dispersal has altered but not erased the phylogeography of the tench

Human-aided dispersal can result in phylogeographic patterns that do not reflect natural historical processes, particularly in species prone to intentional translocations by humans. Here, we use a multiple-gene sequencing approach to assess the effects of human-aided dispersal on phylogeography of the tench Tinca tinca, a widespread Eurasian freshwater fish with a long history in aquaculture. Spatial genetic analysis applied to sequence data from four unlinked loci and 67 geographic localities (38–382 gene copies per locus) defined two groups of populations that were little structured geographically but were significantly differentiated from each other, and it identified locations of major genetic breaks, which were concordant across genes and were driven by distributions of two phylogroups. This pattern most reasonably reflects isolation in two major glacial refugia and subsequent range expansions, with the Eastern and Western phylogroups remaining largely allopatric throughout the tench range. However, this phylogeographic variation was also present in all 17 cultured breeds studied, and some populations at the western edge of the native range contained the Eastern phylogroup. Thus, natural processes have played an important role in structuring tench populations, but human-aided dispersal has also contributed significantly, with the admixed genetic composition of cultured breeds most likely contributing to the introgression

Complex evolutionary history of the Mexican stoneroller Campostoma ornatum Girard, 1856 (Actinopterygii: Cyprinidae)

<p>Abstract</p> <p>Background</p> <p>Studies of the phylogeography of Mexican species are steadily revealing genetic patterns shared by different species, which will help to unravel the complex biogeographic history of the region. <it>Campostoma ornatum </it>is a freshwater fish endemic to montane and semiarid regions in northwest Mexico and southern Arizona. Its wide range of distribution and the previously observed morphological differentiation between populations in different watersheds make this species a useful model to investigate the biogeographic role of the Sierra Madre Occidental and to disentangle the actions of Pliocene tecto-volcanic processes <it>vs </it>Quaternary climatic change. Our phylogeographic study was based on DNA sequences from one mitochondrial gene (<it>cytb</it>, 1110 bp, n = 285) and two nuclear gene regions (S7 and RAG1, 1822 bp in total, n = 56 and 43, respectively) obtained from 18 to 29 localities, in addition to a morphological survey covering the entire distribution area. Such a dataset allowed us to assess whether any of the populations/lineages sampled deserve to be categorised as an evolutionarily significant unit.</p> <p>Results</p> <p>We found two morphologically and genetically well-differentiated groups within <it>C. ornatum</it>. One is located in the northern river drainages (Yaqui, Mayo, Fuerte, Sonora, Casas Grandes, Santa Clara and Conchos) and another one is found in the southern drainages (Nazas, Aguanaval and Piaxtla). The split between these two lineages took place about 3.9 Mya (CI = 2.1-5.9). Within the northern lineage, there was strong and significant inter-basin genetic differentiation and also several secondary dispersal episodes whit gene homogenization between drainages. Interestingly, three divergent mitochondrial lineages were found in sympatry in two northern localities from the Yaqui river basin.</p> <p>Conclusions</p> <p>Our results indicate that there was isolation between the northern and southern phylogroups since the Pliocene, which was related to the formation of the ancient Nazas River paleosystem, where the southern group originated. Within groups, a complex reticulate biogeographic history for <it>C. ornatum </it>populations emerges, following the taxon pulse theory and mainly related with Pliocene tecto-volcanic processes. In the northern group, several events of vicariance promoted by river or drainage isolation episodes were found, but within both groups, the phylogeographic patterns suggest the occurrence of several events of river capture and fauna interchange. The Yaqui River supports the most diverse populations of <it>C. ornatum</it>, with several events of dispersal and isolation within the basin. Based on our genetic results, we defined three ESUs within <it>C. ornatum </it>as a first attempt to promote the conservation of the evolutionary processes determining the genetic diversity of this species. They will likely be revealed as a valuable tool for freshwater conservation policies in northwest Mexico, where many environmental problems concerning the use of water have rapidly arisen in recent decades.</p

Harmful algal blooms and eutrophication : examining linkages from selected coastal regions of the United States

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Harmful Algae 8 (2008): 39-53, doi:10.1016/j.hal.2008.08.017.Coastal waters of the United States (U.S.) are subject to many of the major harmful algal bloom (HAB) poisoning syndromes and impacts. These include paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), ciguatera fish poisoning (CFP) and various other HAB phenomena such as fish kills, loss of submerged vegetation, shellfish mortalities, and widespread marine mammal mortalities. Here, the occurrences of selected HABs in a selected set of regions are described in terms of their relationship to eutrophication, illustrating a range of responses. Evidence suggestive of changes in the frequency, extent or magnitude of HABs in these areas is explored in the context of the nutrient sources underlying those blooms, both natural and anthropogenic. In some regions of the U.S., the linkages between HABs and eutrophication are clear and well documented, whereas in others, information is limited, thereby highlighting important areas for further research.Support was provided through the Woods Hole Center for Oceans and Human Health (to DMA), National Science Foundation (NSF) grants OCE-9808173 and OCE-0430724 (to DMA), OCE-0234587 (to WPC), OCE04-32479 (to MLP), OCE-0138544 (to RMK), OCE-9981617 (to PMG); National Institute of Environmental Health Sciences (NIEHS) grants P50ES012742-01 (to DMA) and P50ES012740 (to MLP); NOAA Grants NA96OP0099 (to DMA), NA16OP1450 (to VLT), NA96P00084 (to GAV and CAH), NA160C2936 and NA108H-C (to RMK), NA860P0493 and NA04NOS4780241 (to PMG), NA04NOS4780239-02 (to RMK), NA06NOS4780245 (to DWT). Support was also provided from the West Coast Center for Oceans and Human Health (to VLT and WPC), USEPA Grant CR826792-01-0 (to GAV and CAH), and the State of Florida Grant S7701617826 (to GAV and CAH)