Profitability and Pricing in Treasury Bill Auctions: Evidence from Pakistan

Behaviour in the first three years of auctions for Pakistani treasury bills is studied. Bidding strategies rapidly converged to a consistent pattern after the auctions started in 1991. Factors that influenced the expected profitability of auction participation are identified. Auction participation was on average low and did not differ between types of bidders. Prices bids are found to reflect both ‘buy and sell’ and ‘buy and hold’ strategies, and were affected by risk considerations and bidder-specific variables. The Pakistani experience suggests the robustness of auctions as a market-based allocation mechanism, and their value in public debt management.

Profitability and Pricing in Treasury Bill Auctions: Evidence from Pakistan

Behaviour in the first three years of auctions for Pakistani treasury bills is studied. Bidding strategies rapidly converged to a consistent pattern after the auctions started in 1991. Factors that influenced the expected profitability of auction participation are identified. Auction participation was on average low and did not differ between types of bidders. Prices bids are found to reflect both ‘buy and sell’ and ‘buy and hold’ strategies, and were affected by risk considerations and bidder-specific variables. The Pakistani experience suggests the robustness of auctions as a market-based allocation mechanism, and their value in public debt management

Nicotine Directly Induces Endoplasmic Reticulum Stress Response in Rat Placental Trophoblast Giant Cells

Nicotine exposure during pregnancy leads to placental insufficiency impairing both fetal and neonatal development. Previous studies from our laboratory have demonstrated that in rats,nicotine augmented endoplasmic reticulum (ER) stress in association with placental insufficiency, however, the underlying mechanisms remain elusive. Therefore, we sought to investigate the possible direct effect of nicotine on ER stress in Rcho-1 rat placental trophoblastgiant (TG) cells during differentiation. Protein and/or mRNA expression of markers involved in ER stress (e.g., phosphorylated PERK, eIF2α, CHOP, BiP/GRP78) and trophoblast giant cell differentiation and function (e.g., Pl-1, Pgf, Hsd11b1, and Hsd11b2) were quantified via Western blot or Real-Time PCR. Nicotine treatment led to dose-dependent increases in the phosphorylation of PERK[Thr981] and eIF2α[Ser51], whereas pre-treatment with a nicotinic acetylcholine receptor (nAChR) antagonist (mecamylamine hydrochloride) blocked the induction of PERK phosphorylation, verifying the direct involvement of nicotine and nAChR binding. We next investigated select target genes known to play essential roles in placental TG cell differentiation and function (Pl-1, Pgf, Hsd11b1, and Hsd11b2), and found that nicotine significantly augmented the mRNA levels of Hsd11b1 in a dose-dependent manner. Furthermore, using Tauroursodeoxycholic acid (TUDCA), a safe bile acid known to improve protein chaperoning and folding, we were able to prevent nicotine-induced increases in both PERK phosphorylation and Hsd11b1 mRNA levels, revealing a potential novel therapeutic approach to reverse the deleterious effects of nicotine exposure in pregnancy. Collectively, these results implicate that nicotine, acting through its receptor, can directly augment ER stress and impair placental function

Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as ‘‘natural’’ and ‘‘safe’’ as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of D9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat placentas from vehicle and CBD (3 mg/kg intraperitoneal injection) exposed pregnancies (E6.5-18.5). Results: The study revealed that pups from CBD-exposed pregnancies were 10% smaller, with the placentae displaying a decreased fetal blood space perimeter-to-area ratio. The transcriptomic analysis supported compromised angiogenesis and blood vessel formation with downregulated biological processes, including tube morphogenesis, angiogenesis, blood vessel morphogenesis, blood vessel development and vasculature development. Further, the CBD-exposed placentas displayed changed expression of glucose transporters (decreased GLUT1 and GR expression and increased GLUT3 expression). Transcriptomic analysis further revealed upregulated biological processes associated with metabolism. Finally, histological and transcriptomic analysis revealed altered cell populations within the placenta, specifically to syncytiotrophoblast layer II and endothelial cells. Conclusion: Together these results suggest that the structural changes in CDB-exposed placentae, including the altered expression of nutrient transporters and the changes to the placental fetal vasculature, may underlie the reduced fetal growth. https://www.liebertpub.com/doi/10.1089/can.2023.016

Maternal Nicotine Exposure Leads to Augmented Expression of the Antioxidant Adipose Tissue Triglyceride Lipase Long-Term in the White Adipose of Female Rat Offspring.

Globally, approximately 10-25% of women smoke during pregnancy. Since nicotine is highly addictive, women may use nicotine containing products like nicotine replacement therapies for smoking cessation, but the long-term consequences of early life exposure to nicotine remain poorly defined. Our laboratory has previously demonstrated that maternal nicotine exposed (MNE) rat offspring exhibit hypertriglyceridemia due to increased hepatic de novo lipogenesis. Hypertriglyceridemia may also be attributed to impaired white adipose tissue (WAT) lipid storage; however, the effects of MNE on WAT are not completely understood. We hypothesize that nicotine-induced alterations in adipose function (e.g. lipid storage) underlie dyslipidemia in MNE adults. Female 6 month old rats exposed to nicotine during gestation and lactation exhibited significantly decreased visceral adipocyte cell area by 40%, attributed, in part, to a 3-fold increase in adipose triglyceride lipase (ATGL) protein expression compared to vehicle. Given ATGL has antioxidant properties and in utero nicotine exposure promotes oxidative stress in various tissues, we next investigated if there was evidence of increased oxidative stress in MNE WAT. At both 3 weeks and 6 months, MNE offspring expressed 37-48% higher protein levels of SOD1 and SOD2 in WAT. Since oxidative stress can induce inflammation, we examined the inflammatory profile of WAT and found increased expression of cytokines (IL-1β, TNFα, and IL-6) by 44-61% at 6 months. Collectively, this suggests that the expression of WAT ATGL may be induced to counter MNE-induced oxidative stress and inflammation. However, higher levels of ATGL would further promote lipolysis in WAT, culminating in impaired lipid storage and long-term dyslipidemia

Characterisation of an Advanced Nickel Based Superalloy Post Cold Work by Swaging

Cylindrical bars of the advanced nickel based superalloy RR1000 were subjected to swaging to induce approximately 30% cold work. Grain size analysis demonstrated a distinct modification to the microstructure whilst electron back scattered diffraction (EBSD) measurements confirmed the evolution of a relatively strong texture parallel with the longitudinal bar axis. Intragranular strain damage was identified. The effects of the swaging on bulk mechanical properties are illustrated across a range of test temperatures

Adverse effects of perinatal nicotine exposure on reproductive outcomes

Nicotine exposure during pregnancy through cigarette smoking, nicotine replacement therapies or e-cigarette use continues to be a widespread public health problem, impacting both fetal and postnatal health. Yet, at this time, there remains limited data regarding the safety and efficacy in using these nicotine products during pregnancy. Notably, reports assessing the effect of nicotine exposure on postnatal health outcomes in humans, including reproductive health, are severely lacking. Our current understanding regarding the consequences of nicotine exposure during pregnancy is limited to a few animal studies, which do not comprehensively address the underlying cellular mechanisms involved. This paper aims to critically review the current knowledge from human and animal studies regarding the direct and indirect effects (e.g. obesity) of maternal nicotine exposure, regardless of its source, on reproductive outcomes in pregnancy and postnatal life. Furthermore, this review highlights several key cellular mechanisms involved in these adverse reproductive deficits including oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By understanding the interplay of the cellular mechanisms involved, further strategies could be developed to prevent the reproductive abnormalities resulting from exposure to nicotine in utero and influence informed clinical guidelines for pregnant women

Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice

We have examined the regulatory role of the individual components of the immunoglobulin antigen receptor in B-cell development by transgenic complementation of Rag-1 deficient (Rag-1⁻) mice. Complementation with a membrane µ heavy chain (µHC) gene allows progression of developmentally arrested Rag-1⁻ pro-B-cells to the small pre-B cell stage, whereas the introduction of independently integrated µHC and κ light chain (κLC) transgenes promotes the appearance of peripheral lymphocytes which, however, remain unresponsive to external stimuli. Complete reconstitution of the B-cell lineage and the emergence of functionally nature Rag-1⁻ peripheral B cells is achieved by the introduction of cointegrated heavy and light chain transgenes encoding an anti-H-2^k antibody. This experimental system demonstrates the competence of the µHC and κLC to direct and regulate the sequential stages of B-cell differentiation, defines the time at which negative selection of self-reactive B cells occurs, and shows that elimination of these cells occurs equally well in the absence of Rag-1 as in its presence. These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process

Signatures of Galaxy-Cluster Interactions: Spiral Galaxy Rotation Curve Asymmetry, Shape, and Extent

The environmental dependencies of the characteristics of spiral galaxy rotation curves are studied in this work. We use our large, homogeneously collected sample of 510 cluster spiral galaxy rotation curves to test the claim that the shape of a galaxy's rotation curve strongly depends on its location within the cluster, and thus presumably on the strength of the local intracluster medium and on the frequency and strength of tidal interactions with the cluster and cluster galaxies. Our data do not corroborate such a scenario, consistent with the fact that Tully-Fisher residuals are independent of galaxy location within the cluster; while the average late-type spiral galaxy shows more rise in the outer parts of its rotation curve than does the typical early-type spiral galaxy, there is no apparent trend for either subset with cluster environment. We also investigate as a function of cluster environment rotation curve asymmetry and the radial distribution of H II region tracers within galactic disks. Mild trends with projected cluster-centric distance are observed: (i) the (normalized) radial extent of optical line emission averaged over all spiral galaxy types shows a 4%+/-2% increase per Mpc of galaxy-cluster core separation, and (ii) rotation curve asymmetry falls by a factor of two between the inner and outer cluster for early-type spirals (a negligible decrease is found for late-type spirals). Such trends are consistent with spiral disk perturbations or even the stripping of the diffuse, outermost gaseous regions within the disks as galaxies pass through the dense cluster cores.Comment: 17 pages; to appear in the April 2001 Astronomical Journa