Effects of Cadmium, Calcium, Age and Parity on Bone Mineral, Density and Strength in Female Rats

Weanling female rats were fed diets containing one of three levels of Ca (0.3, 0.6 or 0.9%) and one of four levels of Cd (0, 1, 5 or 10 ppm) in the drinking water. One half of each group was bred first as adolescents (55 days) and the other half as mature (110 days) females. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppm Cd were smaller at birth than offspring of dams treated with 0 or 1 ppm Cd. After the fourth pregnancy, the decreased birth weight was evident only in offspring of dams treated with 10 ppm Cd. Offspring of dams fed 5 or 10 ppm Cd or the 0.3% Ca diet had decreased weaning weight regardless of parity. A 0.3% Ca diet superimposed upon a 5 or 10 ppm Cd intake decreased weaning weight of the male offspring after the first, but not the fourth, pregnancy with the offspring of adolescent dams affected more than those of mature dams. Offspring of dams fed the 0.9% Ca diet did not differ in weaning weight from the offspring of dams fed the 0.6% Ca diet. Cadmium treatment had no effect on the plasma Ca or the Ca-P ratio. At Cd levels of 5 or 10 ppm the plasma P was increased. The 0.3% Ca diet depressed the plasma Ca the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet. Parity did not affect plasma Ca but, after four pregnancies, plasma P was decreased. Plasma Ca of mature dams was higher than that of adolescent dams but plasma P was unaffected. Bone mineral, density and strength were decreased by the 0.3% Ca diet especially when Cd levels reached 10 ppm. Increasing dietary Ca above normal increased femur Ca of dams fed 1 ppm Cd but did not increase the Ca of the femur of dams given higher levels of Cd. After the first pregnancy, femur Ca of mature dams was greater than that of adolescent dams. After the fourth pregnancy, femurs of mature dams were less strong than those of adolescent dams; however, the density was the same. Increasing dietary Ca above 0.6% lessened the detrimental effects of 5 ppm Cd ingestion on bone density. Mature dams were less affected by the 0.3% Ca 10 ppm Cd treatment than were adolescent dams

Amplification and nonlinear mechanisms in plane Couette flow

We study the input-output response of a streamwise constant projection of the Navier-Stokes equations for plane Couette flow, the so-called 2D/3C model. Study of a streamwise constant model is motivated by numerical and experimental observations that suggest the prevalence and importance of streamwise and quasi-streamwise elongated structures. Periodic spanwise/wall-normal (z–y) plane stream functions are used as input to develop a forced 2D/3C streamwise velocity field that is qualitatively similar to a fully turbulent spatial field of direct numerical simulation data. The input-output response associated with the 2D/3C nonlinear coupling is used to estimate the energy optimal spanwise wavelength over a range of Reynolds numbers. The results of the input-output analysis agree with previous studies of the linearized Navier-Stokes equations. The optimal energy corresponds to minimal nonlinear coupling. On the other hand, the nature of the forced 2D/3C streamwise velocity field provides evidence that the nonlinear coupling in the 2D/3C model is responsible for creating the well known characteristic “S” shaped turbulent velocity profile. This indicates that there is an important tradeoff between energy amplification, which is primarily linear, and the seemingly nonlinear momentum transfer mechanism that produces a turbulent-like mean profile

Bringing Together Academic and Industrial Chemistry: Edmund Ronalds’ Contribution

Born 200 years ago, Edmund Ronalds (1819–1889) obtained his doctorate in Germany under Liebig, became a professor at Queen’s College Galway and ran the little-studied but significant Bonnington Chemical Works in Edinburgh. His few mentions in the modern literature relate generally to the legacies of his actual and assumed academic supervisors of renown, yet his hitherto unknown mentors included family members and the important chemists Graham, Magnus, Tennant and Tennent. The novelty of his shift from university to manufacture has also been noted. With the aid of little-known primary sources, this biography details the evolution of Ronalds’ career, exploring the context and influences for his diverse accomplishments and in particular the new and successful ways he bridged academia and industry through technological education and industrial research

A Novel Role for Stat1 in Phagosome Acidification and Natural Host Resistance to Intracellular Infection by Leishmania major

Intracellular parasites of the genus Leishmania generate severe diseases in humans, which are associated with a failure of the infected host to induce a protective interferon γ (IFNγ)-mediated immune response. We tested the role of the JAK/STAT1 signaling pathway in Leishmania pathogenesis by utilizing knockout mice lacking the signal transducer and activator of transcription 1 (Stat1) and derived macrophages. Unexpectedly, infection of Stat1-deficient macrophages in vitro with promastigotes from Leishmania major and attenuated LPG1 knockout mutants (lpg−) specifically lacking lipophosphoglycan (LPG) resulted in a twofold increased intracellular growth, which was independent of IFNγ and associated with a substantial increase in phagosomal pH. Phagosomes in Stat1−/− macrophages showed normal maturation as judged by the accumulation of the lysosomal marker protein rab7, and provided normal vATPase activity, but were defective in the anion conductive pathway required for full vesicular acidification. Our results suggest a role of acidic pH in the control of intracellular Leishmania growth early during infection and identify for the first time an unexpected role of Stat1 in natural anti-microbial resistance independent from its function as IFNγ-induced signal transducer. This novel Stat1 function may have important implications to studies of other pathogens, as the acidic phagolysosomal pH plays an important role in antigen processing and the uncoating process of many viruses

Rapid turnover of T cells in acute infectious mononucleosis.

During acute infectious mononucleosis (AIM), large clones of Epstein-Barr virus-specific T lymphocytes are produced. To investigate the dynamics of clonal expansion, we measured cell proliferation during AIM using deuterated glucose to label DNA of dividing cells in vivo, analyzing cells according to CD4, CD8 and CD45 phenotype. The proportion of labeled CD8(+)CD45R0(+) T lymphocytes was dramatically increased in AIM subjects compared to controls (mean 17.5 versus 2.8%/day; p<0.005), indicating very rapid proliferation. Labeling was also increased in CD4(+)CD45R0(+) cells (7.1 versus 2.1%/day; p<0.01), but less so in CD45RA(+) cells. Mathematical modeling, accounting for death of labeled cells and changing pool sizes, gave estimated proliferation rates in CD8(+)CD45R0(+) cells of 11-130% of cells proliferating per day (mean 47%/day), equivalent to a doubling time of 1.5 days and an appearance rate in blood of about 5 x 10(9) cells/day (versus 7 x 10(7) cells/day in controls). Very rapid death rates were also observed amongst labeled cells (range 28-124, mean 57%/day),indicating very short survival times in the circulation. Thus, we have shown direct evidence for massive proliferation of CD8(+)CD45R0(+) T lymphocytes in AIM and demonstrated that rapid cell division continues concurrently with greatly accelerated rates of cell disappearance

An exploration of patients’ experience of nurses’ use of point-of-care information technology in acute care

The rapid introduction of technology into acute healthcare settings, specifically the presence of point-of-care health information technology at patients’ bedsides, is expected to impact patients’ healthcare experience by altering nurse-patient interactions. This research was a multi-method naturalistic pilot study designed to explore patients’ perception of their interactions with nurses using bedside point-of-care health information technology in acute care. Data were collected using observation, interviews and surveys. Twenty-four participants were purposefully recruited from medical and surgical wards, to capture variability in their self-reported confidence with information technology; 29% were not confident, 38% were somewhat confident and 33% were completely confident with information technology. Participants’ mean age was 68.6 years (SD 11.1) and 63% were male. Qualitative observation, interview and survey data showed some nurses directly involved patients and explained or demonstrated how the point-of-care health information technology was being used to complement and enhance their care; while others used the point-of-care health information technology as an electronic documentation tool without engaging their patients. Patients’ experiences of point-of-care health information technology differed with their self-reported confidence with information technology; those with complete information technology confidence were better at recognising the potential and opportunities for point-of-care health information technology to support self-directed care than those with less confidence using information technology. Some participants reported that the use of point-of-care health information technology impeded interpersonal communication with nurses. Participants recognised the benefits of point-of-care health information technology to support clinical practice but generally desired greater engagement with the nurses when they used the system

Expanded proteomic survey of the human parasite Leishmania major focusing on changes in null mutants of the Golgi GDP-mannose/fucose/arabinopyranose transporter

The trypanosomatid protozoan parasit

Perioperative Neurocognitive Disorder: State of the Preclinical Science.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research

Differential Effects of MitoVitE, α-Tocopherol and Trolox on Oxidative Stress, Mitochondrial Function and Inflammatory Signalling Pathways in Endothelial Cells Cultured under Conditions Mimicking Sepsis

Funding: This research was funded by The British Journal of Anaesthesia/Royal College of Anaesthetists (PhD studentship to Beverley Minter). Acknowledgments: We are very grateful to Professor M.P. Murphy, MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, UK for the generous gift of MitoVitE used in all the experiments, without which this work would not have been possible.Peer reviewedPublisher PD

The land plant-specific MIXTA-MYB lineage is implicated in the early evolution of the plant cuticle and the colonization of land.

The evolution of a lipid-based cuticle on aerial plant surfaces that protects against dehydration is considered a fundamental innovation in the colonization of the land by the green plants. However, key evolutionary steps in the early regulation of cuticle synthesis are still poorly understood, owing to limited studies in early-diverging land plant lineages. Here, we characterize a land plant specific subgroup 9 R2R3 MYB transcription factor MpSBG9, in the early-diverging land plant model Marchantia polymorpha, that is homologous to MIXTA proteins in vascular plants. The MpSBG9 functions as a key regulator of cuticle biosynthesis by preferentially regulating expression of orthologous genes for cutin formation, but not wax biosynthesis genes. The MpSBG9 also promotes the formation of papillate cells on the adaxial surface of M. polymorpha, which is consisitent with its canonical role in vascular plants. Our observations imply conserved MYB transcriptional regulation in the control of the cutin biosynthesis pathway as a core genetic network in the common ancestor of all land plants, implicating the land plant-specific MIXTA MYB lineage in the early origin and evolution of the cuticle