Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II

The classically recognized functions of the renin–angiotensin system are mediated by type 1 (AT1) angiotensin receptors. Whereas man possesses a single AT1 receptor, there are two AT1 receptor isoforms in rodents (AT1A and AT1B) that are products of separate genes (Agtr1a and Agtr1b). We have generated mice lacking AT1B (Agtr1b −/−) and both AT1A and AT1B receptors (Agtr1a −/−Agtr1b −/−). Agtr1b −/− mice are healthy, without an abnormal phenotype. In contrast, Agtr1a −/−Agtr1b −/− mice have diminished growth, vascular thickening within the kidney, and atrophy of the inner renal medulla. This phenotype is virtually identical to that seen in angiotensinogen-deficient (Agt−/−) and angiotensin-converting enzyme-deficient (Ace −/−) mice that are unable to synthesize angiotensin II. Agtr1a −/−Agtr1b −/− mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine. Blood pressure is reduced substantially in the Agtr1a −/− Agtr1b −/− mice and following administration of an angiotensin converting enzyme inhibitor, their blood pressure increases paradoxically. We suggest that this is a result of interruption of AT2-receptor signaling. In summary, our studies suggest that both AT1 receptors promote somatic growth and maintenance of normal kidney structure. The absence of either of the AT1 receptor isoforms alone can be compensated in varying degrees by the other isoform. These studies reaffirm and extend the importance of AT1 receptors to mediate physiological functions of the renin–angiotensin system.

Homologs of FT, CEN and FD respond to developmental and environmental signals affecting growth and flowering in the perennial vine kiwifruit

FLOWERING LOCUS T (FT) and CENTRORADIALIS (CEN) homologs have been implicated in regulation of growth, determinacy and flowering. The roles of kiwifruit FT and CEN were explored using a combination of expression analysis, protein interactions, response to temperature in high-chill and low-chill kiwifruit cultivars and ectopic expression in Arabidopsis and Actinidia. The expression and activity of FT was opposite from that of CEN and incorporated an interaction with a FLOWERING LOCUS D (FD)-like bZIP transcription factor. Accumulation of FT transcript was associated with plant maturity and particular stages of leaf, flower and fruit development, but could be detected irrespective of the flowering process and failed to induce precocious flowering in transgenic kiwifruit. Instead, transgenic plants demonstrated reduced growth and survival rate. Accumulation of FT transcript was detected in dormant buds and stem in response to winter chilling. In contrast, FD in buds was reduced by exposure to cold. CEN transcript accumulated in developing latent buds, but declined before the onset of dormancy and delayed flowering when ectopically expressed in kiwifruit. Our results suggest roles for FT, CEN and FD in integration of developmental and environmental cues that affect dormancy, budbreak and flowering in kiwifruit.

Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine

SPARC (secreted protein acidic and rich in cysteine)/ osteonectin/BM-40 is a matricellular protein implicated in development, cell transformation and tumorigenesis. We have examined the role of SPARC in cell transformation induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA) and 12- tetradecanoylphorbol-13-acetate (TPA) in embryonic fibroblasts and in the skin of mice. Embryonic fibroblasts from SPARCnull mice showed increases in cell proliferation, enhanced sensitivity to DMBA and a higher number of DMBA/TPA-induced transformation foci. The number of DMBA-DNA adducts was 9 times higher in SPARCnull fibroblasts and their stability was lower than wild-type fibroblasts, consistent with a reduction in excision repair cross-complementing 1 the nucleotide excision repair enzyme in these cells. The SPARCnull mice showed an increase in both the speed and number of papillomas forming after topical administration of DMBA/TPA to the skin. These papillomas showed reduced growth and reduced progression to a more malignant phenotype, indicating that the effect of SPARC on tumorigenesis depends upon the transformation stage and/or tissue context. These data reinforce a growing number of observations in which SPARC has shown opposite effects on different tumor types/stages.

Identification of genes important for growth of asymptomatic bacteriuria Escherichia coli in urine

Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine.

Limb-loss in pond-reared blue swimmer crabs Portunus pelagicus (L.): Effect on growth in an indoor shedding system

Limb-loss in crustaceans can reduce moult increment and delay or advance the timing of moulting, both aspects that are likely to impact upon soft-shell crab production. Pond-reared blue swimmer crabs Portunus pelagicus were harvested and maintained in a crab shedding system. The wet weight, carapace width (CW) and the occurrence of limb-loss were assessed before stocking in the shedding system and after each of the next three moults. Many of the crabs were initially missing one or two limbs and these did not grow as much as the crabs that were intact at the start of the trial. Despite its strong correlation with wet weight, CW changes proved to be misleading. Limb-loss reduced the %CW increment but not the per cent weight increment (where the later is calculated from the actual pre-moult weight). Pre-moult weight explained much of the variation in post-moult weight, with crabs moulting to approximately double their weight. Limb-loss reduced 'growth' and production from the pond because it reduced pre-moult weight but limb-loss did not alter the weight change on shedding a given weight of crabs, although some of that change now included regeneration of limbs. One can hypothesize that much of the size variation seen in pond-reared crabs may be due to accumulated effects of repeated limb-loss, rather than genetic variation.

Growth in the Asian elephant

Records of captive Asian elephants (Elephas maximus) were used to derive parameters of the von Bertalanffy function for growth in height, body weight and circumference of tusks with age. There was some evidence for a post-pubertal secondary growth spurt in both male and female elephants. Domestic elephants which were born in captivity or captured at a young age also showed a reduced growth in height in both the sexes and in body weight in males compared to wild elephants. Aspects of allometric growth such as height-body weight relationship are examined. The height was twice the circumference of front foot throughout the life span, indicating an isometric relationship.

Ontogenetic patterns and temperature-dependent growth rates in early life stages of Pacific cod (Gadus macrocephalus)

Pacific cod (Gadus macrocephalus) is an important component of fisheries and food webs in the North Pacific Ocean and Bering Sea. However, vital rates of early life stages of this species have yet to be described in detail. We determined the thermal sensitivity of growth rates of embryos, preflexion and postflexion larvae, and postsettlement juveniles. Growth rates (length and mass) at each ontogenetic stage were measured in three replicate tanks at four to five temperatures. Nonlinear regression was used to obtain parameters for independent stage-specific growth functions and a unified size- and temperature-dependent growth function. Specific growth rates increased with temperature at all stages and generally decreased with increases in body size. However, these analyses revealed a departure from a strict size-based allometry in growth patterns, as reduced growth rates were observed among preflexion larvae: the reduction in specific growth rate between embryos and free-swimming larvae was greater than expected based on body size differences. Growth reductions in the preflexion larvae appear to be associated with increased metabolic rates and the transition from endogenous to exogenous feeding. In future studies, experiments should be integrated across life transitions to more clearly define intrinsic ontogenetic and size-dependent growth patterns because these are critical for evaluations of spatial and temporal variation in habitat quality.

Seasonal marine growth of Bristol Bay sockeye salmon (Oncorhynchus nerka) in relation to competition with Asian pink salmon (O. gorbuscha) and the 1977 ocean regime shift

Recent research demonstrated significantly lower growth and survival of Bristol Bay sockeye salmon (Oncorhynchus nerka) during odd-numbered years of their second or third years at sea (1975, 1977, etc.), a trend that was opposite that of Asian pink salmon (O. gorbuscha) abundance. Here we evaluated seasonal growth trends of Kvichak and Egegik river sockeye salmon (Bristol Bay stocks) during even- and odd-numbered years at sea by measuring scale circuli increments within each g rowth zone of each major salmon age group between 1955 and 2000. First year scale growth was not significantly different between odd- and even-numbered years, but peak growth of age-2 smolts was significantly higher than age-1. smolts. Total second and third year scale growth of salmon was significantly lower during odd- than during even-numbered years. However, reduced scale growth in odd-numbered years began after peak growth in spring and continued through summer and fall even though most pink salmon had left the high seas by late July (10−18% growth reduction in odd vs. even years). The alternating odd and even year growth pattern was consistent before and after the 1977 ocean reg ime shift. During 1977−2000, when salmon abundance was relatively great, sockeye salmon growth was high during specific seasons compared with that during 1955−1976, that is to say, immediately after entry to Bristol Bay, after peak growth in the first year, during the middle of the second growing season, and during spring of the third season. Growth after the spring peak in the third year at sea was relatively low during 1977−2000. We hypothesize that high consumption rates of prey by pink salmon during spring through mid-July of odd-numbered years, coupled with declining zooplankton biomass during summer and potentially cyclic abundances of squid and other prey, contributed to reduced prey availability and therefore reduced growth of Bristol Bay sockeye salmon during late spring through fall of odd-numbered years.

Empirically modelling the potential effects of changes in temperature and prey availability on the growth of cod larvae in UK shelf seas

It has been hypothesized that changes in zooplankton community structure over the past four decades led to reduced growth and survival of prerecruit Atlantic cod (Gadus morhua) and that this was a key factor underlying poor year classes, contributing to stock collapse, and inhibiting the recovery of stocks around the UK. To evaluate whether observed changes in plankton abundance, species composition and temperature could have led to periods of poorer growth of cod larvae, we explored the effect of prey availability and temperature on early larval growth using an empirical trophodynamic model. Prey availability was parameterized using species abundance data from the Continuous Plankton Recorder. Our model suggests that the observed changes in plankton community structure in the North Sea may have had less impact on cod larval growth, at least for the first 40 days following hatching, than previously suggested. At least in the short term, environmental and prey conditions should be able to sustain growth of cod larvae and environmental changes acting on this early life stage should not limit stock recovery.

Calmodulin disruption impacts growth and motility in juvenile liver fluke

Background: Deficiencies in effective flukicide options and growing issues with drug resistance make current strategies for liver fluke control unsustainable, thereby promoting the need to identify and validate new control targets in Fasciola spp. parasites. Calmodulins (CaMs) are small calcium-sensing proteins with ubiquitous expression in all eukaryotic organisms and generally use fluctuations in intracellular calcium levels to modulate cell signalling events. CaMs are essential for fundamental processes including the phosphorylation of protein kinases, gene transcription, calcium transport and smooth muscle contraction. In the blood fluke Schistosoma mansoni, calmodulins have been implicated in egg hatching, miracidial transformation and larval development. Previously, CaMs have been identified amongst liver fluke excretory-secretory products and three CaM-like proteins have been characterised biochemically from adult Fasciola hepatica, although their functions remain unknown.

Methods: In this study, we set out to investigate the biological function and control target potential of F. hepatica CaMs (FhCaMs) using RNAi methodology alongside novel in vitro bioassays.

Results: Our results reveal that: (i) FhCaMs are widely expressed in parenchymal cells throughout the forebody region of juvenile fluke; (ii) significant transcriptional knockdown of FhCaM1-3 was inducible by exposure to either long (~200 nt) double stranded (ds) RNAs or 27 nt short interfering (si) RNAs, although siRNAs were less effective than long dsRNAs; (iii) transient long dsRNA exposure-induced RNA interference (RNAi) of FhCaMs triggered transcript knockdown that persisted for ≥ 21 days, and led to detectable suppression of FhCaM proteins; (iv) FhCaM RNAi significantly reduced the growth of juvenile flukes maintained in vitro; (v) FhCaM RNAi juveniles also displayed hyperactivity encompassing significantly increased migration; (vi) both the reduced growth and increased motility phenotypes were recapitulated in juvenile fluke using the CaM inhibitor trifluoperazine hydrochloride, supporting phenotype specificity.

Conclusions: These data indicate that the Ca(2+)-modulating functions of FhCaMs are important for juvenile fluke growth and movement and provide the first functional genomics-based example of a growth-defect resulting from gene silencing in liver fluke. Whilst the phenotypic impacts of FhCaM silencing on fluke behaviour do not strongly support their candidature as new flukicide targets, the growth impacts encourage further consideration, especially in light of the speed of juvenile fluke growth in vivo.

Regulated deficit irrigation - a means to control growth in woody ornamentals

Improving plant quality and the uniformity of a crop are major objectives for growers of ornamental nursery stock. The potential to control excess vigour and to improve quality through regulated deficit irrigation (RDI) was investigated using a range of woody ornamental species. RDI regimes reduced vegetative growth consistently across different species and growing seasons. Plants adapted to reduced water supplies primarily via stomatal control, but also by osmotic adjustment when grown under the most severe RDI regimes. Only plants exposed to <= 25% of potential evapo-transpiration demonstrated any evidence of leaf injury, and the extent was slight. Growth inhibition increased as the severity of RDI increased. Improvements in quality were attained through a combination of shorter internodes and final shoot lengths, yet the number of 'formative' primary shoots remained unaffected. Compact, well-branched plants could be formed without a requirement for mid-season pruning. In addition to severity, the timing of RDI also influenced growth responses. Applying 50% ETp for 8 weeks during July-August resulted in the formation of good quality plants, which retained their shape until the following Spring. Re-positioning irrigation drippers within the pots of well-watered plants, in an attempt to induce a partial root drying (PRD) treatment, reduced growth, but not significantly. The adoption of irrigation scheduling, based on 50-100% ETp, has the potential to improve commercial crop quality across a range of ornamental species.

Seasonal changes in vegetative growth and photosynthesis of Arabica coffee trees

Seasonal changes in vegetative growth, leaf gas exchanges, carbon isotope discrimination (Delta) and carbohydrate status were monitored in de-fruited coffee trees (Coffea arabica L.) grown in the field, from October 1998 through September 1999, in Vicosa (20degrees45'S, 42degrees15'W, 650 m a.s.l.), southeastern Brazil. of the total growth over the 12-month study period, 78% occurred in the warm, rainy season (October-March), and 22% during the cool, dry season (April-September). Throughout the active growth period, the rate of net carbon assimilation (A) averaged 8.6 mumol m(-2) s(-1), against 3.4 mumol m(-2) s(-1) during the period of reduced growth. In the active period, growth, unlike A or Delta, was strongly negatively correlated with air temperature. In contrast, growth and A were both correlated positively, and Delta correlated negatively, with air temperature during the reduced growth period. However, the depressions of A and growth might have simply run in parallel, without any causal relationship. Changes in A appeared to be largely due to stomatal limitations in the active growing season, with non-stomatal ones prevailing in the slow growth period. Foliar carbohydrates seemed not to have contributed appreciably to changes in growth rates and photosynthesis. (C) 2004 Elsevier B.V. All rights reserved.

Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during beta cell carcinogenesis

Members of the vascular endothelial growth factor (VEGF) family are critical players in angiogenesis and lymphangiogenesis. Although VEGF-A has been shown to exert fundamental functions in physiologic and pathologic angiogenesis, the exact role of the VEGF family member placental growth factor (PlGF) in tumor angiogenesis has remained controversial. To gain insight into PlGF function during tumor angiogenesis, we have generated transgenic mouse lines expressing human PlGF-1 in the beta cells of the pancreatic islets of Langerhans (Rip1PlGF-1). In single-transgenic Rip1PlGF-1 mice, intra-insular blood vessels are found highly dilated, whereas islet physiology is unaffected. Upon crossing of these mice with the Rip1Tag2 transgenic mouse model of pancreatic beta cell carcinogenesis, tumors of double-transgenic Rip1Tag2;Rip1PlGF-1 mice display reduced growth due to attenuated tumor angiogenesis. The coexpression of transgenic PlGF-1 and endogenous VEGF-A in the beta tumor cells of double-transgenic animals causes the formation of low-angiogenic hPlGF-1/mVEGF-A heterodimers at the expense of highly angiogenic mVEGF-A homodimers resulting in diminished tumor angiogenesis and reduced tumor infiltration by neutrophils, known to contribute to the angiogenic switch in Rip1Tag2 mice. The results indicate that the ratio between the expression levels of two members of the VEGF family of angiogenic factors, PlGF-1 and VEGF-A, determines the overall angiogenic activity and, thus, the extent of tumor angiogenesis and tumor growth.

In Utero Exposure to Antiretroviral Drugs: Effect on Birth Weight and Growth Among HIV-exposed Uninfected Children in Brazil.

BACKGROUND There are concerns about the effects of in utero exposure to antiretroviral drugs (ARVs) on the development of HIV-exposed but uninfected (HEU) children. The aim of this study was to evaluate whether in utero exposure to ARVs is associated with lower birth weight/height and reduced growth during the first 2 years of life. METHODS This cohort study was conducted among HEU infants born between 1996 and 2010 in Tertiary children's hospital in Rio de Janeiro, Brazil. Weight was measured by mechanical scale, and height was measured by measuring board. Z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length were calculated. We modeled trajectories by mixed-effects models and adjusted for mother's age, CD4 cell count, viral load, year of birth and family income. RESULTS A total of 588 HEU infants were included of whom 155 (26%) were not exposed to ARVs, 114 (19%) were exposed early (first trimester) and 319 (54%) later. WAZ were lower among infants exposed early compared with infants exposed later: adjusted differences were -0.52 (95% confidence interval [CI]: -0.99 to -0.04, P = 0.02) at birth and -0.22 (95% CI: -0.47 to 0.04, P = 0.10) during follow-up. LAZ were lower during follow-up: -0.35 (95% CI: -0.63 to -0.08, P = 0.01). There were no differences in weight-for-length scores. Z-scores of infants exposed late during pregnancy were similar to unexposed infants. CONCLUSIONS In HEU children, early exposure to ARVs was associated with lower WAZ at birth and lower LAZ up to 2 years of life. Growth of HEU children needs to be monitored closely.

Growth response of an early successional assemblage of coralline algae and benthic diatoms to ocean acidification

The sustained absorption of anthropogenically released atmospheric CO2 by the oceans is modifying seawater carbonate chemistry, a process termed ocean acidification (OA). By the year 2100, the worst case scenario is a decline in the average oceanic surface seawater pH by 0.3 units to 7.75. The changing seawater carbonate chemistry is predicted to negatively affect many marine species, particularly calcifying organisms such as coralline algae, while species such as diatoms and fleshy seaweed are predicted to be little affected or may even benefit from OA. It has been hypothesized in previous work that the direct negative effects imposed on coralline algae, and the direct positive effects on fleshy seaweeds and diatoms under a future high CO2 ocean could result in a reduced ability of corallines to compete with diatoms and fleshy seaweed for space in the future. In a 6-week laboratory experiment, we examined the effect of pH 7.60 (pH predicted to occur due to ocean acidification just beyond the year 2100) compared to pH 8.05 (present day) on the lateral growth rates of an early successional, cold-temperate species assemblage dominated by crustose coralline algae and benthic diatoms. Crustose coralline algae and benthic diatoms maintained positive growth rates in both pH treatments. The growth rates of coralline algae were three times lower at pH 7.60, and a non-significant decline in diatom growth meant that proportions of the two functional groups remained similar over the course of the experiment. Our results do not support our hypothesis that benthic diatoms will outcompete crustose coralline algae under future pH conditions. However, while crustose coralline algae were able to maintain their presence in this benthic rocky reef species assemblage, the reduced growth rates suggest that they will be less capable of recolonizing after disturbance events, which could result in reduced coralline cover under OA conditions.