Calcium mediates the interconversion between two states of the liver inositol 1,4,5-trisphosphate receptor

D-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) regulates intracellular Ca2+ by mobilizing Ca2+ from a non-mitochondrial store. We have investigated the effects of Ca2+ on the binding of [32P]Ins (1,4,5)P3 to permeabilized rat hepatocytes and a liver plasma membrane-enriched fraction. Increasing the free Ca2+ concentration in the medium from 0.1 nM to 0.7 microM increased the capacity of a high affinity binding component (KD = 2-3 nM) in permeabilized cells by a factor of 10. If the membrane fraction was preincubated at 37 degrees C before binding was measured at 4 degrees C, all of the Ins(1,4,5)P3 receptors were transformed to a low affinity state (KD = 65 +/- 12 nM, Bmax = 3.1 +/- 0.1 fmol/mg, n = 4). When 0.7 microM of Ca2+ was added, the receptors were totally transformed to a high affinity state (KD = 2.8 +/- 0.4 nM, Bmax = 2.7 +/- 0.4 fmol/mg, n = 4). The EC50 of the Ca2(+)-induced interconversion of the Ins(1,4,5)P3 receptor was 140 nM. This Ca2(+)-induced transformation of the Ins(1,4,5)P3 receptor from a low affinity to a high affinity state was associated with an inhibition of the Ins(1,4,5)P3-induced Ca2+ release in permeabilized hepatocytes. These data suggest that the Ins(1,4,5)P3-dependent hormones, by increasing the intracellular Ca2+ concentration, induce a reversible transformation of the receptor from its low affinity state, coupled to the Ca2+ release, to a desensitized high affinity state. Transformation of the receptor may play a role in the oscillatory release of Ca2+ observed in single isolated hepatocytes.     

Slow O,N-acyl shift in an actinomycin-related peptide lactone

The pentapeptide lactone Cbz-(Thr-D-Val-Pro-Sar-MeAla-) was synthesized in order to observe the behavior of the unprotected lactone resulting from its hydrogenolytic deprotection. Closely related peptide lactones have been reported as intermediates in total syntheses of actinomycin D and its analogues, despite the fact that unprotected and unprotonated O-peptides of serine and threonine are known to undergo rapid O,N-acyl shift. In the present study the peptide lactone was seen to undergo a slow O,N-acyl shift, in a matter of hours, to the known cyclic pentapeptide. This contrasted with the rapid rearrangement of a model O-peptide, O-hippuryl-L-threonine methyl ester. This slowness of an O,N-acyl shift in a cyclic system presumably results from higher energy barriers of conformational origin. It explains the suitability of unprotected peptide lactones for the syntheses of actinomycins and other peptide lactone antibiotics which have appeared in the literature.     

Anti‐angiogenic therapy: Adapting strategies to overcome resistant tumors

Healthy cells, as well as benign and malignant tumors, depend upon the body's blood supply to bring in oxygen and nutrients and carry away waste products. Using this property against tumors, anti‐angiogenic therapy targets the tumor vasculature with the aim of starving the tumor, and has demonstrated exceptional clinical efficacy against a number of tumors. This review discusses the current state of knowledge regarding anti‐angiogenic therapies presently available to patients, and garners from both preclinical and clinical literature the benefits and side effects associated with anti‐angiogenic therapies, the unfortunate mechanisms of acquired resistance to these novel therapeutics, and highlights promising next generation anti‐angiogenics that may overcome the limitations encountered with first generation therapies. J. Cell. Biochem. 111: 543–553, 2010. © 2010 Wiley‐Liss, Inc.     

Quantitative trait loci for foliar terpenes in a global eucalypt species

Terpenes are a diverse group of plant secondary metabolites that mediate a plethora of ecological interactions in many plant species. Despite increasing research into the genetic control of important adaptive traits in some plant species, the genetic control of terpenes in forest tree species is still relatively poorly studied. In this study, we use quantitative genetic and quantitative trait loci (QTL) analysis to investigate the genetic control of foliar terpenes in an ecologically and commercially important eucalypt species, Eucalyptus globulus. We show a moderate to high within-family broad-sense heritability and significant genetic basis to the variation in 14 of the 16 terpenes assayed. This is the first report of QTL for terpenes in this species. Eleven QTL influenced the terpenes overall. One QTL on linkage group 6 affected six of the seven different sesquiterpenes assayed (plus one monoterpene), which, in combination with highly significant correlations between these compounds, argues that their variation is influenced by a QTL with pleiotropic effect early in the biosynthetic pathway. We examine the homology of these QTL to those found in a closely related eucalypt, Eucalyptus nitens, and provide evidence that both common and unique QTL influence terpene levels.     

Quantifying Characters: Polygenist Anthropologists and the Hardening of Heredity

Scholars studying the history of heredity suggest that during the 19th-century biologists and anthropologists viewed characteristics as a collection of blended qualities passed on from the parents. Many argued that those characteristics could be very much affected by environmental circumstances, which scholars call the inheritance of acquired characteristics or “soft” heredity. According to these accounts, Gregor Mendel reconceived heredity – seeing distinct hereditary units that remain unchanged by the environment. This resulted in particular traits that breed true in succeeding generations, or “hard” heredity. The author argues that polygenist anthropology (an argument that humanity consisted of many species) and anthropometry in general should be seen as a hardening of heredity. Using a debate between Philadelphia anthropologist and physician, Samuel G. Morton, and Charleston naturalist and reverend, John Bachman, as a springboard, the author contends that polygenist anthropologists hardened heredity by conceiving of durable traits that might reappear even after a race has been eliminated. Polygenists saw anthropometry (the measurement of humans) as one method of quantifying hereditary qualities. These statistical ranges were ostensibly characteristics that bred true and that defined racial groups. Further, Morton’s interest in hybridity and racial mixing demonstrates that the polygenists focused as much on the transmission and recognition of “amalgamations” of characters as they did on racial categories themselves. The author suggests that seeing race science as the study of heritable, statistical characteristics rather than broad categories helps explain why “race” is such a persistent cultural phenomenon.     

Fine-Scale Distribution and Spatial Variability of Benthic Invertebrate Larvae in an Open Coastal Embayment in Nova Scotia,Canada

This study quantified the fine- scale (0.5 km) of variability in the horizontal distributions of benthic invertebrate larvae and related this variability to that in physical and biological variables, such as density, temperature, salinity, fluorescence and current velocity. Larvae were sampled in contiguous 500-m transects along two perpendicular 10-km transects with a 200-µm plankton ring net (0.75-m diameter) in St. George’s Bay, Nova Scotia, Canada, in Aug 2009. Temperature, conductivity, pressure and fluorescence were measured with a CTD cast at each station, and currents were measured with an Acoustic Doppler Current Profiler moored at the intersection of the 2 transects. Gastropod, bivalve and, to a lesser extent, bryozoan larvae had very similar spatial distributions, but the distribution of decapod larvae had a different pattern. These findings suggest that taxonomic groups with functionally similar larvae have similar dispersive properties such as distribution and spatial variability, while the opposite is true for groups with functionally dissimilar larvae. The spatial variability in larval distributions was anisotropic and matched the temporal/spatial variability in the current velocity. We postulate that in a system with no strong oceanographic features, the scale of spatially coherent physical forcing (e.g. tidal periodicity) can regulate the formation or maintenance of larval patches; however, swimming ability may modulate it.     

Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes: The ADD-CKD Study (Awareness,Detection and Drug Therapy in Type 2 Diabetes and Chronic Kidney Disease)

This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1–5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3–5 CKD than Stages 1 and 2. There were no differences in clinicians’ likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.     

Initiation and characterization of five embryonic cell lines from the cotton boll weevil anthonomus grandis in a commercial serum- free medium

Summary Five continuous cell lines were initiated from embryonic tissue of the cotton boll weevilAnthonomus grandis Boheman in a commercially available, serum-free medium (Excell 401) and have undergone in excess of 60 passages. Isoenzyme analysis confirmed that the lines originated from boll weevil tissue. Four of the lines grew as single attached cells of either epithelioid or fibroblastoid morphology. The fifth line, BRL-AG-2, grew primarily as cell aggregates and was found to release ecdysteroids (primarily ecdysone) into the culture medium. Evidence was also obtained suggesting that line BRL-AG-2 synthesizes chitin. Three lines, BRL-AG-1, BRL-AG-3A, and BRL-AG-3C, could be induced to produce an antibacterial factor(s) which was released into the culture medium.     

Does drainage pay? Quantifying agricultural profitability associated with wetland drainage practices and canola production in Alberta

Conversion of wetlands in cultivated agricultural landscapes is one of the primary drivers of wetland loss in Alberta, Canada, despite a provincial wetland policy that prioritizes wetland avoidance. While other sectors of the agricultural industry have established initiatives to maintain wetlands, a common narrative within the conventional cropping sector is that wetland retention leads to lost acreage and overlap of crop inputs, and that there are financial benefits associated with wetland drainage. The objective of this research was to explicitly quantify crop productivity within drained wetland basins, in an effort to better understand the extent to which producers financially benefit from drainage practices. Working collaboratively with canola producers in central Alberta over the 2019 growing season, wetland basins within four quarter sections were mapped using an Unmanned Aerial Vehicle, and wetland basins with clear evidence of surface drainage were identified. Agricultural input and yield data provided by producers was then used to quantify profitability within each drained basin. Average profit for drained basins for each producer ranged between ? $145/acre and $76/acre, with an average of $55/acre across all operations. This is compared to an average profit of $203/acre for non-wetland areas across all operations. The results suggest that the financial benefits of drainage are highly variable, and for many drained basins, producers may experience financial losses that may be overlooked when profits are examined only at the field- or operation-level. While this study included a small number of operations, and was limited to one type of crop over a single growing season, the results still provide important insight into the extent to which producers benefit financially from the practice of wetland drainage.