Nitrate-Rich Groundwater Inputs To Discovery Bay, Jamaica - A Significant Source Of N To Local Coral Reefs

The freshwater aquifer at Discovery Bay, Jamaica, produces subterranean springs and seeps near the reef at the mouth and along the southern and western shorelines of the bay. A strong inverse correlation exists between salinity and N concentration. Undiluted springwater typically contains 80 J.Lg at N per liter or more, primarily as nitrate, but is essentially devoid of P. Input from the springs is enough to reduce the salinity by one to several parts per thousand near these sites and appears to produce a significant enrichment of nitrogen to the bay

Perseveration by NK1R-/- ('knockout') mice is blunted by doses of methylphenidate that affect neither other aspects of their cognitive performance nor the behaviour of wild-type mice in the 5-Choice Continuous Performance Test

The underlying cause(s) of abnormalities expressed by patients with attention deficit hyperactivity disorder (ADHD) have yet to be delineated. One factor that has been associated with increased vulnerability to ADHD is polymorphism(s) ofTACR1, which is the human equivalent of the rodent NK1 (substance P-preferring) receptor gene (Nk1r). We have reported previously that genetically altered mice, lacking functional NK1R (NK1R-/-), express locomotor hyperactivity, which was blunted by the first-line treatment for ADHD, methylphenidate. Here, we compared the effects of this psychostimulant (3, 10 and 30 mg/kg, intraperitoneally) on the behaviour of NK1R-/- mice and their wild types in the 5-Choice Continuous Performance Test, which emulates procedures used to study attention and response control in ADHD patients. Methylphenidate increased total trials (a measure of 'productivity') completed by wild types, but not by NK1R-/- mice. Conversely, this drug reduced perseveration by NK1R-/- mice, but not by wild types. Other drug-induced changes in key behaviours were not genotype dependent, especially at the highest dose: for example, % omissions (an index of inattentiveness) was increased, whereas % false alarms and % premature responses (measures of impulsivity) declined in both genotypes, indicating reduced overall response. These findings are discussed in the context of the efficacy of methylphenidate in the treatment of ADHD. Moreover, they lead to several testable proposals. First, methylphenidate does not improve attention in a subgroup of ADHD patients with a functional deficit of TACR1. Second, these patients do not express excessive false alarms when compared with other groups of subjects, but they do express excessive perseveration, which would be ameliorated by methylphenidate

Diffusion-controlled phase growth on dislocations

We treat the problem of diffusion of solute atoms around screw dislocations. In particular, we express and solve the diffusion equation, in radial symmetry, in an elastic field of a screw dislocation subject to the flux conservation boundary condition at the interface of a new phase. We consider an incoherent second-phase precipitate growing under the action of the stress field of a screw dislocation. The second-phase growth rate as a function of the supersaturation and a strain energy parameter is evaluated in spatial dimensions d=2 and d=3. Our calculations show that an increase in the amplitude of dislocation force, e.g. the magnitude of the Burgers vector, enhances the second-phase growth in an alloy. Moreover, a relationship linking the supersaturation to the precipitate size in the presence of the elastic field of dislocation is calculated.Comment: 10 pages, 4 figures, a revised version of the paper presented in MS&T'08, October 5-9, 2008, Pittsburg

Differences in the performance of NK1R−/− (‘knockout’) and wildtype mice in the 5‑Choice Continuous Performance Test

Mice lacking functional NK1 (substance P‑preferring) receptors typically display excessive inattentiveness (omission errors) and impulsivity (premature responses) when compared with wildtypes in the 5‑Choice Serial Reaction‑Time Test (5‑CSRTT). These abnormal behaviours are analogous to those seen in humans suffering from Attention Deficit Hyperactivity Disorder (ADHD). Here we used the 5‑Choice Continuous‑Performance Test (5C‑CPT) to ascertain whether NK1R-/- mice also display excessive false alarms (an inappropriate response to a 'no-go' signal), which is another form of impulsive behaviour. NK1R-/- mice completed more trials than wildtypes, confirming their ability to learn and carry out the task. At the start of Stage 1 of training, but not subsequently, they also scored more premature responses than wildtypes. When the mice were tested for the first time, neither false alarms nor premature responses was higher in NK1R-/- mice than wildtypes but, as in the 5‑CSRTT, the latter behaviour was strongly dependent on time of day. NK1R-/- mice expressed excessive perseveration during all stages of the 5C‑CPT. This behaviour is thought to reflect compulsive checking, which is common in ADHD patients. These findings point to differences in the 5‑CSRTT and 5C‑CPT protocols that could be important for distinguishing why the cognitive performance and response control of NK1R-/- mice differs from their wildtypes. The results further lead to the prediction that ADHD patients with polymorphism of the TACR1 gene (the human equivalent of Nk1r) would express more perseveration, but not false alarms, in Continuous Performance Tests when compared with other groups of subjects

Shareholder Theory/Shareholder Value

Shareholder theory states that the primary objective of management is to maximize shareholder value. This objective ranks in front of the interests of other corporate stakeholders, such as employees, suppliers, customers, and society.Shareholder theory argues that shareholders are the ultimate owners of a corporate’s assets, and thus, the priority for managers and boards is to protect and grow these assets for the benefit of shareholders. Shareholder theory assumes that shareholders value corporate assets with two measurable metrics, dividends and share price. There-fore, management should make decisions that maximize the combined value of dividends and share price increases. However, shareholder theory fails to consider that shareholders and corporates may have other objectives that are not based on financial performance. For example, as early as1932, Berle and Means argued that corporations have a variety of purposes and interests including encouraging entrepreneurship, innovation, and building communities. This wider view is gaining more traction in recent decades as evidenced by an increased interest in ethical investment funds.This suggests that shareholders and potential shareholders are not only interested in financial gains but are also interested in corporates being socially responsible (Kyriakou2018). Therefore shareholder value creation is important; however,it needs to be balanced with other stakeholders’ interests. This is referred to as an enlightened approach to shareholder value maximization

The paleobiological record of photosynthesis

Fossil evidence of photosynthesis, documented in Precambrian sediments by microbially laminated stromatolites, cyanobacterial microscopic fossils, and carbon isotopic data consistent with the presence of Rubisco-mediated CO2-fixation, extends from the present to ~3,500 million years ago. Such data, however, do not resolve time of origin of O2-producing photoautotrophy from its anoxygenic, bacterial, evolutionary precursor. Though it is well established that Earth’s ecosystem has been based on autotrophy since its very early stages, the time of origin of oxygenic photosynthesis, more than 2,450 million years ago, has yet to be established

RAPID AND RELIABLE HEALING OF CRITICAL SIZE BONE DEFECTS WITH GENETICALLY MODIFIED SHEEP MUSCLE

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease