LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway

LST8, a Saccharomyces cerevisiae gene encoding a 34-kD WD-repeat protein, was identified by mutations that caused defects in sorting Gap1p to the plasma membrane. Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accumulation of high levels of intracellular amino acids, which signal Gap1p sorting to the vacuole. To identify the essential function of Lst8p, we isolated lst8 mutants that are temperature-sensitive for growth. These mutants show hypersensitivity to rapamycin and derepressed Gln3p activity like cells with compromised TOR pathway activity. Like tor2 mutants, lst8 mutants also have cell wall integrity defects. Confirming a role for Lst8p in the TOR pathway, we find that Lst8p associates with both Tor1p and Tor2p and is a peripheral membrane protein that localizes to endosomal or Golgi membranes and cofractionates with Tor1p. Further, we show that a sublethal concentration of rapamycin mimics the Gap1p sorting defect of an lst8 mutant. Finally, the different effects of lst8 alleles on the activation of either the Rtg1/3p or Gln3p transcription factors reveal that these two pathways constitute distinct, genetically separable outputs of the Tor–Lst8 regulatory complex

Room Temperature In-plane <100> Magnetic Easy Axis for Fe3O4/SrTiO3(001):Nb Grown by Infrared PLD

We examine the magnetic easy-axis directions of stoichiometric magnetite films grown on SrTiO3:Nb by infrared pulsed-laser deposition. Spin-polarized low-energy electron microscopy reveals that the individual magnetic domains are magnetized along the in-plane film directions. Magneto-optical Kerr effect measurements show that the maxima of the remanence and coercivity are also along in-plane film directions. This easy-axis orientation differs from bulk magnetite and films prepared by other techniques, establishing that the magnetic anisotropy can be tuned by film growth.Comment: 3 pages, 3 figure

Patency of arterial repairs from wartime extremity vascular injuries

Background: Extremity vascular injury (EVI) causes significant disability in Veterans of the Afghanistan/Iraq conflicts. Advancements in acute trauma care improved survival and decreased amputations. The study of wartime EVI has relied on successful limb salvage as a surrogate for vascular repair. We used imaging studies as a specific measure of arterial repair durability. Methods: Service members with EVI were identified using the Department of Defense Trauma Registry and validated by chart abstraction. Inclusion criteria for the arterial patency subgroup included an initial repair attempt with subsequent imaging reports (duplex ultrasound, CT angiography, and angiogram) documenting initial patency. Results: The cohort of 527 included 140 Veterans with available imaging studies for 143 arterial repairs; median follow-up from injury time to last available imaging study was 19 months (Q1-Q3: 3-58; range: 1-175). Injury mechanism was predominantly explosions (52%) and gunshot wounds (42%). Of the 143 arterial repairs, 81% were vein grafts. Eight repairs were occluded, replaced or included in extremity amputations. One upper extremity and three transtibial late amputations were performed for chronic pain and poor function averaging 27 months (SD: 4; range: 24-32). Kaplan-Meier analysis estimated patency rates of 99%, 97%, 95%, 91% and 91% at 3, 6, 12, 24, and 36 months, respectively, with similar results for upper and lower extremity repairs. Explosive and gunshot wound injury mechanisms had similar patency rates and upper extremity injuries repaired with vein grafts had increased patency. Conclusions: Arterial repair mid-term patency in combat-related extremity injuries is excellent based on imaging studies for 143 repairs. Assertive attempts at acute limb salvage and vascular repair are justified with decisions for amputation versus limb salvage based on the overall condition of the patient and degree of concomitant nerve, orthopedic and soft tissue injuries rather than the presence of arterial injuries. Level of evidence: Therapeutic/care management, level IV

Inter-Rater Reliability of Historical Data Collected by Non-Medical Research Assistants and Physicians in Patients with Acute Abdominal Pain

OBJECTIVES: In many academic emergency departments (ED), physicians are asked to record clinical data for research that may be time consuming and distracting from patient care. We hypothesized that non-medical research assistants (RAs) could obtain historical information from patients with acute abdominal pain as accurately as physicians.METHODS: Prospective comparative study conducted in an academic ED of 29 RAs to 32 resident physicians (RPs) to assess inter-rater reliability in obtaining historical information in abdominal pain patients. Historical features were independently recorded on standardized data forms by a RA and RP blinded to each others' answers. Discrepancies were resolved by a third person (RA) who asked the patient to state the correct answer on a third questionnaire, constituting the "criterion standard." Inter-rater reliability was assessed using kappa statistics (kappa) and percent crude agreement (CrA).RESULTS: Sixty-five patients were enrolled (mean age 43). Of 43 historical variables assessed, the median agreement was moderate (kappa 0.59 [Interquartile range 0.37-0.69]; CrA 85.9%) and varied across data categories: initial pain location (kappa 0.61 [0.59-0.73]; CrA 87.7%), current pain location (kappa 0.60 [0.47-0.67]; CrA 82.8%), past medical history (kappa 0.60 [0.48-0.74]; CrA 93.8%), associated symptoms (kappa 0.38 [0.37-0.74]; CrA 87.7%), and aggravating/alleviating factors (kappa 0.09 [-0.01-0.21]; CrA 61.5%). When there was disagreement between the RP and the RA, the RA more often agreed with the criterion standard (64% [55-71%]) than the RP (36% [29-45%]).CONCLUSION: Non-medical research assistants who focus on clinical research are often more accurate than physicians, who may be distracted by patient care responsibilities, at obtaining historical information from ED patients with abdominal pain

Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen

Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus, a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines

Intermediate band to conduction band optical absorption in ZnTeO

ZnTe doped with high concentrations of oxygen has been proposed in previous works as an intermediate band (IB) material for photovoltaic applications. The existence of extra optical transitions related to the presence of an IB has already been demonstrated in this material and it has been possible to measure the absorption coefficient of the transitions from the valence band (VB) to the IB. In this study, we present the first measurement of the absorption coefficient associated with transitions from the IB to the conduction band (CB) in ZnTeO. The samples used are 4-μm-thick ZnTe layers with or without O in a concentration ~1019 cm-3, which have been grown on semiinsulating GaAs substrates by molecular beam epitaxy (MBE). The IB-CB absorption coefficient peaks for photon energies ~0.4 eV. It is extracted from reflectance and transmittance spectra measured using Fourier transform infrared (FTIR) spectroscopy. Under typical FTIR measurement conditions (low light intensity, broadband spectrum), the absorption coefficient in IB-to-CB transitions reaches 700 cm-1. This is much weaker than the one observed for VB-IB absorption. This result is consistent with the fact that the IB is expected to be nearly empty of electrons under equilibrium conditions in ZnTe(O).Peer Reviewe

Zwitterionic PEG-PC hydrogels modulate the foreign body response in a modulus-dependent manner

Reducing the foreign body response (FBR) to implanted biomaterials will enhance their performance in tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are increasingly popular for this application due to their low cost, ease of use, and the ability to tune their compliance via molecular weight and crosslinking densities. PEG hydrogels can elicit chronic inflammation in vivo, but recent evidence has suggested that extremely hydrophilic, zwitterionic materials and particles can evade the immune system. To combine the advantages of PEG-based hydrogels with the hydrophilicity of zwitterions, we synthesized hydrogels with co-monomers PEG and the zwitterion phosphorylcholine (PC). Recent evidence suggests that stiff hydrogels elicit increased immune cell adhesion to hydrogels, which we attempted to reduce by increasing hydrogel hydrophilicity. Surprisingly, hydrogels with the highest amount of zwitterionic co-monomer elicited the highest FBR we observed. Lowering the hydrogel modulus (165 kPa to 3 kPa), or PC content (20 wt% to 0 wt%), mitigated this effect. A high density of macrophages was found at the surface of implants associated with a high FBR, and mass spectrometry analysis of the proteins adsorbed to these gels implicated extracellular matrix, immune response, and cell adhesion protein categories as drivers of macrophage recruitment to these hydrogels. Overall, we show that modulus regulates macrophage adhesion to zwitterionic-PEG hydrogels, and demonstrate that chemical modifications to hydrogels should be studied in parallel with their physical properties to optimize implant design

Author Correction: Rapidly-migrating and internally-generated knickpoints can control submarine channel evolution (Nature Communications, (2020), 11, 1, (3129), 10.1038/s41467-020-16861-x)

© 2020, The Author(s). The original version of this Article contained an error in the labelling of the cross-section in Fig. 2g and the vertical axis in Fig. 2b. This has been corrected in both the PDF and HTML versions of the Article

Intermediate band to conduction band optical absorption in ZnTeO

ZnTe doped with high concentrations of oxygen has been proposed in previous works as an intermediate band (IB) material for photovoltaic applications. The existence of extra optical transitions related to the presence of an IB has already been demonstrated in this material and it has been possible to measure the absorption coefficient of the transitions from the valence band (VB) to the IB. In this study, we present the first measurement of the absorption coefficient associated with transitions from the IB to the conduction band (CB) in ZnTeO. The samples used are 4-mum-thick ZnTe layers with or without O in a concentration ~10 19 cm -3, which have been grown on semiinsulating GaAs substrates by molecular beam epitaxy (MBE). The IB-CB absorption coefficient peaks for photon energies ~0.4 eV. It is extracted from reflectance and transmittance spectra measured using Fourier transform infrared (FTIR) spectroscopy. Under typical FTIR measurement conditions (low light intensity, broadband spectrum), the absorption coefficient in IB-to-CB transitions reaches 700 cm -1. This is much weaker than the one observed for VB-IB absorption. This result is consistent with the fact that the IB is expected to be nearly empty of electrons under equilibrium conditions in ZnTe(O)