Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of up to 200,000 infant deaths a year, through the effects of placental insufficiency leading to growth restriction and preterm delivery. Development of a vaccine is one strategy for control. Plasmodium falciparum-infected red blood cells accumulate in the placenta through specific binding of pregnancy-associated parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the potential to cause placental damage and compromise foetal growth. Multigravid women develop immunity towards VAR2CSA-expressing parasites in a gravidity-dependent manner which prevents unfavourable pregnancy outcomes. Although current vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies artificially, this candidate may not provide protection during the first trimester and may only protect those women living in areas endemic for malaria. It is concluded that while insufficient information about placental-parasite interactions is presently available to produce an effective vaccine, incremental progress is being made towards achieving this goal

Chemistry by Mobile Phone (or how to justify more time at the bar)

By combining automatic environment monitoring with Java smartphones a system has been produced for the real-time monitoring of experiments whilst away from the lab. Changes in the laboratory environment are encapsulated as simple XML messages, which are published using an MQTT compliant broker. Clients subscribe to the MQTT stream, and produce a user display. An MQTT client written for the Java MIDP platform, can be run on a smartphone with a GPRS Internet connection, freeing us from the constraints of the lab. We present an overview of the technologies used, and how these are helping chemists make the best use of their time

Cancer Survivorship: A Growing Role for Physiatric Care

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146952/1/pmr2527.pd

Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24.

Off-target binding of hydrophobic drugs can lead to unwanted side effects, either through specific or non-specific binding to unintended membrane protein targets. However, distinguishing the binding of drugs to membrane proteins from that of detergents, lipids and cofactors is challenging. Here, we use high-resolution mass spectrometry to study the effects of HIV protease inhibitors on the human zinc metalloprotease ZMPSTE24. This intramembrane protease plays a major role in converting prelamin A to mature lamin A. We monitored the proteolysis of farnesylated prelamin A peptide by ZMPSTE24 and unexpectedly found retention of the C-terminal peptide product with the enzyme. We also resolved binding of zinc, lipids and HIV protease inhibitors and showed that drug binding blocked prelamin A peptide cleavage and conferred stability to ZMPSTE24. Our results not only have relevance for the progeria-like side effects of certain HIV protease inhibitor drugs, but also highlight new approaches for documenting off-target drug binding

Acid Polishing of Lead Crystal Glass

The industrial partner manufactures high quality lead crystal glassware. The cutting of decorative features in the glass damages the surface and the cuts are optically opaque; to restore transparency, the glass is polished in a solution of hydrofluoric (HF) and sulphuric acid (H2 SO4 .) The polishing process comprises three stages: 1. immersion in a polishing tank containing acid; 2. rinsing in a tank containing water; and 3. settlement of the solid reaction products in a settlement tank. The manufacturer hopes to optimise its polishing process to • minimise the health/environmental impact of the process; • maximise throughput; • maintain the sharpness of the cut edges while still polishing to an acceptable level of transparency. The study group was asked to focus on modelling three aspects of the process: • the chemical reactions involved in the etching at the glass-acid solution interface; • the removal of reaction products in the settlement tank; • flow within the polishing tank

PinR mediates the generation of reversible population diversity in Streptococcus zooepidemicus

Opportunistic pathogens must adapt to and survive in a wide range of complex ecosystems. Streptococcus zooepidemicus is an opportunistic pathogen of horses and many other animals, including humans. The assembly of different surface architecture phenotypes from one genotype is likely to be crucial to the successful exploitation of such an opportunistic lifestyle. Construction of a series of mutants revealed that a serine recombinase, PinR, inverts 114 bp of the promoter of SZO_08560, which is bordered by GTAGACTTTA and TAAAGTCTAC inverted repeats. Inversion acts as a switch, controlling the transcription of this sortase-processed protein, which may enhance the attachment of S. zooepidemicus to equine trachea. The genome of a recently sequenced strain of S. zooepidemicus, 2329 (Sz2329), was found to contain a disruptive internal inversion of 7 kb of the FimIV pilus locus, which is bordered by TAGAAA and TTTCTA inverted repeats. This strain lacks pinR and this inversion may have become irreversible following the loss of this recombinase. Active inversion of FimIV was detected in three strains of S. zooepidemicus, 1770 (Sz1770), B260863 (SzB260863) and H050840501 (SzH050840501), all of which encoded pinR. A deletion mutant of Sz1770 that lacked pinR was no longer capable of inverting its internal region of FimIV. The data highlight redundancy in the PinR sequence recognition motif around a short TAGA consensus and suggest that PinR can reversibly influence the wider surface architecture of S. zooepidemicus, providing this organism with a bet-hedging solution to survival in fluctuating environments

Summer 1975

Getting Back to Basics--Turfgrass Fertilization (page 3) Carefree Herbaceous Perennials For Gardens and Borders (9) Back and Beyond (10) Turf News--New Lifting Technique accepted (14) Vandalism on Golf Courses (15) UMass Turfgrass Research Fund (20

Recent Developments

Context. Tracing nuclear inflows and outflows in active galactic nuclei (AGNs), determining the mass of gas involved in them, and their impact on the host galaxy and nuclear black hole requires 3D imaging studies of both the ionized and molecular gas. Aims. We map the distribution and kinematics of molecular and ionized gas in a sample of active galaxies to quantify the nuclear inflows and outflows. Here, we analyze the nuclear kinematics of NGC 1566 via ALMA observations of the CO J:2-1 emission at 24 pc spatial and ∼2.6 km s−1 spectral resolution, and Gemini-GMOS/IFU observations of ionized gas emission lines and stellar absorption lines at similar spatial resolution, and 123 km s−1 of intrinsic spectral resolution. Methods. The morphology and kinematics of stellar, molecular (CO), and ionized ([N II]) emission lines are compared to the expectations from rotation, outflows, and streaming inflows. Results. While both ionized and molecular gas show rotation signatures, there are significant non-circular motions in the innermost 200 pc and along spiral arms in the central kpc (CO). The nucleus shows a double-peaked CO profile (full width at zero intensity of 200 km s−1), and prominent (∼80 km s−1) blue- and redshifted lobes are found along the minor axis in the inner arcseconds. Perturbations by the large-scale bar can qualitatively explain all features in the observed velocity field. We thus favor the presence of a molecular outflow in the disk with true velocities of ∼180 km s−1 in the nucleus and decelerating to 0 by ∼72 pc. The implied molecular outflow rate is 5.6 M⊙ yr−1, with this gas accumulating in the nuclear 2″ arms. The ionized gas kinematics support an interpretation of a similar but more spherical outflow in the inner 100 pc, with no signs of deceleration. There is some evidence of streaming inflows of ∼50 km s−1 along specific spiral arms, and the estimated molecular mass inflow rate, ∼0.1 M⊙ yr−1, is significantly higher than the SMBH accretion rate (ṁ = 4.8 × 10−5 M⊙ yr−1)

Mammalian Sleep Dynamics: How Diverse Features Arise From a Common Physiological Framework

Mammalian sleep varies widely, ranging from frequent napping in rodents to consolidated blocks in primates and unihemispheric sleep in cetaceans. In humans, rats, mice and cats, sleep patterns are orchestrated by homeostatic and circadian drives to the sleep–wake switch, but it is not known whether this system is ubiquitous among mammals. Here, changes of just two parameters in a recent quantitative model of this switch are shown to reproduce typical sleep patterns for 17 species across 7 orders. Furthermore, the parameter variations are found to be consistent with the assumptions that homeostatic production and clearance scale as brain volume and surface area, respectively. Modeling an additional inhibitory connection between sleep-active neuronal populations on opposite sides of the brain generates unihemispheric sleep, providing a testable hypothetical mechanism for this poorly understood phenomenon. Neuromodulation of this connection alone is shown to account for the ability of fur seals to transition between bihemispheric sleep on land and unihemispheric sleep in water. Determining what aspects of mammalian sleep patterns can be explained within a single framework, and are thus universal, is essential to understanding the evolution and function of mammalian sleep. This is the first demonstration of a single model reproducing sleep patterns for multiple different species. These wide-ranging findings suggest that the core physiological mechanisms controlling sleep are common to many mammalian orders, with slight evolutionary modifications accounting for interspecies differences