Phycomyces

This monographic review on a fungus is not addressed to mycologists. None of the authors has been trained or has otherwise acquired a general proficiency in mycology. They are motivated by a common interest in the performances of signal handling exhibited by the sense organs of all organisms and by the desire to attack these as yet totally obscure aspects of molecular biology by the study of a microorganism with certain desirable properties. The sporangiophore of the fungus Phycomyces is a gigantic, single-celled, erect, cylindrical, aerial hypha. It is sensitive to at least four distinct stimuli: light, gravity, stretch, and some unknown stimulus by which it avoids solid objects. These stimuli control a common output, the growth rate, producing either temporal changes in growth rate or tropic responses. We are interested in the output because it gives us information about the reception of the various signals. In the absence of external stimuli, the growth rate is controlled by internal signals keeping the network of biochemical processes in balance. The external stimuli interact with the internal signals. We wish to inquire into the early steps of this interaction. For light, for instance, the cell must have a receptor pigment as the first mediator. What kind of a molecule is this pigment? Which organelle contains it? What chemical reaction happens after a light quantum has been absorbed? And how is the information introduced by this primary photochemical event amplified in a controlled manner and processed in the next step? How do a few quanta or a few molecules trigger macroscopic responses? Will we find ourselves confronted with devices wholly distinct from anything now known in biology

Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RationaleAs part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).ObjectivesTo estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.MethodsWe created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.Measurements and main resultsIn the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to$48 billion. These had an incremental cost per QALY of $657,000 to$3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.ConclusionsSubstantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks

E-Liquid Autofluorescence can be used as a Marker of Vaping Deposition and Third-Hand Vape Exposure

In the past 5 years, e-cigarette use has been increasing rapidly, particularly in youth and young adults. Due to the novelty of e-cigarettes (e-cigs) and e-cigarette liquids (e-liquids), research on their chemo-physical properties is still in its infancy. Here, we describe a previously unknown and potentially useful property of e-liquids, namely their autofluorescence. We performed an emission scan at 9 excitation wavelengths common to fluorescent microscopy and found (i) that autofluorescence differs widely between e-liquids, (ii) that e-liquids are most fluorescent in the UV range (between 350 and 405 nm) and (iii) fluorescence intensity wanes as the emission wavelength increases. Furthermore, we used the autofluorescence of e-liquids as a marker for tracking e-cig aerosol deposition in the laboratory. Using linear regression analysis, we were able to quantify the deposition of a "vaped" e-liquid onto hard surfaces. Using this technique, we found that every 70 mL puff of an e-cigarette deposited 0.019% e-liquid (v/v) in a controlled environment. Finally, we vaped a surface in the laboratory and used our method to detect e-cig aerosol third-hand exposure. In conclusion, our data suggest that e-cigarette autofluorescence can be used as a marker of e-cigarette deposition

Modeling Method for Increased Precision and Scope of Directly Measurable Fluxes at a Genome-Scale

Metabolic flux analysis (MFA) is considered to be the gold standard for determining the intracellular flux distribution of biological systems. The majority of work using MFA has been limited to core models of metabolism due to challenges in implementing genome-scale MFA and the undesirable trade-off between increased scope and decreased precision in flux estimations. This work presents a tunable workflow for expanding the scope of MFA to the genome-scale without trade-offs in flux precision. The genome-scale MFA model presented here, iDM2014, accounts for 537 net reactions, which includes the core pathways of traditional MFA models and also covers the additional pathways of purine, pyrimidine, isoprenoid, methionine, riboflavin, coenzyme A, and folate, as well as other biosynthetic pathways. When evaluating the iDM2014 using a set of measured intracellular intermediate and cofactor mass isotopomer distributions (MIDs), it was found that a total of 232 net fluxes of central and peripheral metabolism could be resolved in the <i>E. coli</i> network. The increase in scope was shown to cover the full biosynthetic route to an expanded set of bioproduction pathways, which should facilitate applications such as the design of more complex bioprocessing strains and aid in identifying new antimicrobials. Importantly, it was found that there was no loss in precision of core fluxes when compared to a traditional core model, and additionally there was an overall increase in precision when considering all observable reactions

Chk1 Haploinsufficiency Results in Anemia and Defective Erythropoiesis

Erythropoiesis is a highly regulated and well-characterized developmental process responsible for providing the oxygen transport system of the body. However, few of the mechanisms involved in this process have been elucidated. Checkpoint Kinase 1 (Chk1) is best known for its role in the cell cycle and DNA damage pathways, and it has been shown to play a part in several pathways which when disrupted can lead to anemia.Here, we show that haploinsufficiency of Chk1 results in 30% of mice developing anemia within the first year of life. The anemic Chk1+/- mice exhibit distorted spleen and bone marrow architecture, and abnormal erythroid progenitors. Furthermore, Chk1+/- erythroid progenitors exhibit an increase in spontaneous DNA damage foci and improper contractile actin ring formation resulting in aberrant enucleation during erythropoiesis. A decrease in Chk1 RNA has also been observed in patients with refractory anemia with excess blasts, further supporting a role for Chk1 in clinical anemia.Clinical trials of Chk1 inhibitors are currently underway to treat cancer, and thus it will be important to track the effects of these drugs on red blood cell development over an extended period. Our results support a role for Chk1 in maintaining the balance between erythroid progenitors and enucleated erythroid cells during differentiation. We show disruptions in Chk1 levels can lead to anemia

Differences in beliefs about COVID-19 by gun ownership: a cross-sectional survey of Texas adults

OBJECTIVES: We investigated the association between gun ownership and perceptions about COVID-19 among Texas adults as the pandemic emerged. We considered perceived likelihood that the pandemic would lead to civil unrest, perceived importance of taking precautions to prevent transmission and perceptions that the threat of COVID-19 has been exaggerated. METHODS: Data were collected from 5 to 12 April 2020, shortly after Texas’ stay-at-home declaration. We generated a sample using random digit dial methods for a telephone survey (n=77, response rate=8%) and by randomly selecting adults from an ongoing panel to complete the survey online (n=1120, non-probability sample). We conducted a logistic regression to estimate differences in perceptions by gun ownership. To account for bias associated with use of a non-probability sample, we used Bayesian data integration and ran linear regression models to produce more accurate measures of association. RESULTS: Among the 60% of Texas adults who reported gun ownership, estimates of past 7-day gun purchases, ammunition purchases and gun carrying were 15% (n=78), 20% (n=100) and 24% (n=130), respectively. We found no evidence of an association between gun ownership with perceived importance of taking precautions to prevent transmission or with perceived likelihood of civil unrest. Results from the logistic regression (OR 1.27, 95% CI 0.99 to 1.63) and the linear regression (β=0.18, 95% CI 0.07 to 0.29) suggest that gun owners may be more likely to believe the threat of COVID-19 was exaggerated. CONCLUSIONS: Compared with those without guns, gun owners may have been inclined to downplay the threat of COVID-19 early in the pandemic

Alpha(1)-adrenergic-mediated eNOS phosphorylation in intact arteries

Activation of arterial smooth muscle alpha(1)-adrenergic receptors results in vasoconstriction, as well as a secondary release of nitric oxide and slow vasodilation, presumably through gap junction communication from smooth muscle to endothelium. We hypothesized that this slow vasodilation is due to activation of eNOS through phosphorylation at Ser1179 and dephosphorylation at Thr495. Phosphorylation was measured by western blot using mouse mesenteric arteries that were cannulated and pressurized (75 mm Hg) and treated either by 1) 5 mm of phenylephrine superfusion (10(-5) M) (PE5), 2) 15 min of phenylephrine (PE15), 3) 15 min phenylephrine followed by acetylcholine (10(-4) M) (PE + ACh), or 4) 20 min time control with no treatment (NT) [4-5 arteries pooled per treatment per blot; 5 blots performed]. These treatments allowed correlation between vasomotor changes, namely maximal constriction (PE5), slow vasodilation (PE15), and maximal dilation (PE + ACh), and relative phosphorylation changes. Phosphorylation of eNOS at Ser1179 was increased relative to NT by more than 2-fold at PE5 and remained similarly increased at PE15 and PE + ACh. Phosphotylation of eNOS at Thr495 was less in all treatments relative to NT, but not significantly. Treatment with L-NAME (10(-4) M) or endothelial denudation indicated that the slow dilation in response to phenylephrine was completely due to nitric oxide synthase and was endothelial dependent. These results indicate that eNOS phosphorylation at Ser1179 occurs before the slow dilation and is not actively involved in this vasodilation or dilation to acetylcholine, but may play a permissive role in eNOS activation by other mechanisms. It is not yet known what mechanism is responsible for Ser1179 phosphorylation with phenylephrine stimulation. (C) 2012 Elsevier Inc. All rights reserved

Tectonomagmatic Evolution of Southwestern Laurentia: Insights from Zircon U-Pb Geochronology and Hafnium Isotopic Composition of the Red Bluff Granite Suite, West Texas, USA

We provide laser ablation–multicollector–inductively coupled plasma–mass spectrometry (LA-MC-ICP-MS) and high-precision chemical abrasion–isotope dilution–thermal ionization mass spectrometry (CA-ID-TIMS) U-Pb ages and Hf isotopic compositions of zircons from the Red Bluff Granite Suite and mafic dikes in the Franklin Mountains of El Paso, Texas, USA. Granitoids exposed in the Franklin Mountains were previously divided into five magmatic stages based on cross-cutting relationships. Major and trace element compositions showed that these granitoids are ferroan, alkaline, and A2 type. Homogeneity in the whole-rock geochemistry suggests that the granite stages are genetically related and share similar petrogenetic histories. Weighted mean zircon 206Pb/238U dates from the older magmatic stage 1 alkali-feldspar quartz syenite and stage 2 alkali-feldspar granite are 1112.36 ± 0.35 and 1112.46 ± 0.37 Ma, respectively. The weighted mean εHf(t) values varying from +5.3 to +7.2 are similar to those of other regional ca. 1.1 Ga magmatic rocks throughout southwestern Laurentia. Geochemical characteristics, petrological modeling, and enriched Hf isotopic composition suggest fractional crystallization of a basaltic magma that was produced by melting of an enriched mantle reservoir. However, zircon inheritance ages of ca. 1.3 Ga and 1.26–1.15 Ga are consistent with a minor contribution from felsic crustal basement. Our data and regional geology are consistent with a post-collisional slab break-off that facilitated asthenospheric upwelling and partial melting of the enriched mantle, possibly subcontinental lithospheric mantle, extending from Llano Uplift, Texas, in the southeast to California to the northwest. Magma thus generated upon differentiation produced ferroan and A-type granitoids

Seascape configuration leads to spatially uneven delivery of parrotfish herbivory across a Western Indian Ocean seascape

Spatial configuration of habitat types in multihabitat seascapes influence ecological function through links of biotic and abiotic processes. These connections, for example export of organic matter or fishes as mobile links, define ecosystem functionality across broader spatial scales. Herbivory is an important ecological process linked to ecosystem resilience, but it is not clear how herbivory relates to seascape configuration. We studied how herbivory and bioerosion by 3 species of parrotfish were distributed in a multi-habitat tropical seascape in the Western Indian Ocean (WIO). We surveyed the abundance of three species with different life histories—Leptoscarus vaigiensis (seagrass species), Scarus ghobban (juvenile-seagrass/adults-reefs) and Scarus rubroviolaceus (reef species) —in seagrass meadows and on reefs and recorded their selectivity of feeding substrate in the two habitats. Herbivory rates for L. vaigiensis and S. ghobban and bioerosion for S. rubroviolaceus were then modelled using bite rates for different size classes and abundance and biomass data along seascape gradients (distance to alternative habitat types such as land, mangrove and seagrass). Bioerosion by S. rubroviolaceus was greatest on reefs far from seagrass meadows, while herbivory rates by S. ghobban on reefs displayed the opposite pattern. Herbivory in seagrass meadows was greatest in meadows close to shore, where L. vaigiensis targeted seagrass leaves and S. ghobban the epiphytes growing on them. Our study shows that ecological functions performed by fish are not equally distributed in the seascape and are influenced by fish life history and the spatial configuration of habitats in the seascape. This has implications for the resilience of the system, in terms of spatial heterogeneity of herbivory and bioerosion and should be considered in marine spatial planning and fisheries management