The increasing world demand for human biologics cannot be met by current production platforms based primarily on mammalian cell culture due to prohibitive cost and limited scalability [1]. Recent progress in plant expression vector development, downstream processing, and glycoengineering has established plants as a superior alternative to biologic production [2–4]. Plants not only offer the traditional advantages of proper eukaryotic protein modification, potential low cost, high scalability, and increased safety but also allow the production of biologics at unprecedented speed to control potential pandemics or with specific glycoforms for better efficacy or safety (biobetters) [5, 6]. The approval of the first plant-made biologic (PMB) by the United States Food and Drug Administration (FDA) for treating Gaucher’s disease heralds a new era for PMBs and sparks new innovations in this field [7, 8].

The notable increase in biofuel usage by the road transportation sector in Brazil during recent years has significantly altered the vehicular fuel composition. Consequently, many uncertainties are currently found in particulate matter vehicular emission profiles. In an effort to better characterise the emitted particulate matter, measurements of aerosol physical and chemical properties were undertaken inside two tunnels located in the São Paulo Metropolitan Area (SPMA). The tunnels show very distinct fleet profiles: in the Jânio Quadros (JQ) tunnel, the vast majority of the circulating fleet are light duty vehicles (LDVs), fuelled on average with the same amount of ethanol as gasoline. In the Rodoanel (RA) tunnel, the particulate emission is dominated by heavy duty vehicles (HDVs) fuelled with diesel (5% biodiesel). In the JQ tunnel, PM_2.5 concentration was on average 52 μg m^-3, with the largest contribution of organic mass (OM, 42%), followed by elemental carbon (EC, 17%) and crustal elements (13%). Sulphate accounted for 7% of PM_2.5 and the sum of other trace elements was 10%. In the RA tunnel, PM_2.5 was on average 233 μg m^-3, mostly composed of EC (52%) and OM (39%). Sulphate, crustal and the trace elements showed a minor contribution with 5%, 1%, and 1%, respectively. The average OC : EC ratio in the JQ tunnel was 1.59 ± 0.09, indicating an important contribution of EC despite the high ethanol fraction in the fuel composition. In the RA tunnel, the OC : EC ratio was 0.49 ± 0.12, consistent with previous measurements of diesel-fuelled HDVs. Besides bulk carbonaceous aerosol measurement, polycyclic aromatic hydrocarbons (PAHs) were quantified. The sum of the PAHs concentration was 56 ± 5 ng m^-3 and 45 ± 9 ng m^-3 in the RA and JQ tunnel, respectively. In the JQ tunnel, benzo(a)pyrene (BaP) ranged from 0.9 to 6.7 ng m^-3 (0.02–0.1‰ of PM_2.5)] whereas in the RA tunnel BaP ranged from 0.9 to 4.9 ng m^-3 (0.004–0. 02‰ of PM_2.5), indicating an important relative contribution of LDVs emission to atmospheric BaP.

The rise of antibiotic resistance has emphasized the shortcomings in antibiotic drug development (Boucher et al., 2013). The move from biological based discovery methods to chemical approaches to identify candidates has left the antibiotic pipeline painfully dry (Lewis, 2013). The paucity of compounds that are effective against antibiotic resistant pathogens has led to great interest in antimicrobial peptides (AMPs) as potential solutions to the rise of resistant organisms (Hancock and Sahl, 2006; Fox, 2013). AMPs are short (5–50 amino acid) peptides that are produced by virtually all organisms as part of an innate immune system. There are 2,398 AMPs that have been reported (Antimicrobial Peptide Database—September 2013) and over 80% are cationic AMPs (CAMPs). Most positively charged AMPs interact with anionic bacterial membranes (Schmidtchen and Malmsten, 2013) which leads to a rapid breakdown in membrane function and subsequent cell death (Wimley, 2010). It is this mechanism of action that is of interest as it should be difficult for bacteria to develop resistance against lethal concentrations of CAMPs.

The literature including social media shows that Mexican/Latino immigrants have attracted contempt and have been traditionally objected to as a minority in the U.S. The intent here is to search for historical and other factors that might explain the public antipathy and to identify reasons that could, either in isolation or in combination with others, explain anti-immigrant sentiments among people, many of whom are descendants of immigrants. The perusal of the challenges of Mexican immigrants to the U.S. through the decades will highlight some similarities related to discrimination against waves “peoples of color”, not only in the U.S. but in other parts of the world. The daily treatment within the society of immigrants of color as well as the frequent lower immigration quotas imposed on certain groups, including Mediterranean people, makes the topic quite relevant to today’s concerns.

We tested the hypothesis that motor planning and programming of speech articulation and verbal short-term memory (vSTM) depend on partially overlapping networks of neural regions. We evaluated this proposal by testing 76 individuals with acute ischemic stroke for impairment in motor planning of speech articulation (apraxia of speech, AOS) and vSTM in the first day of stroke, before the opportunity for recovery or reorganization of structure-function relationships. We also evaluated areas of both infarct and low blood flow that might have contributed to AOS or impaired vSTM in each person. We found that AOS was associated with tissue dysfunction in motor-related areas (posterior primary motor cortex, pars opercularis; premotor cortex, insula) and sensory-related areas (primary somatosensory cortex, secondary somatosensory cortex, parietal operculum/auditory cortex); while impaired vSTM was associated with primarily motor-related areas (pars opercularis and pars triangularis, premotor cortex, and primary motor cortex). These results are consistent with the hypothesis, also supported by functional imaging data, that both speech praxis and vSTM rely on partially overlapping networks of brain regions.

Working memory (WM) theoretically affords the ability to privilege social threats and opportunities over other more mundane information, but few experiments have sought support for this contention. Using a functional logic, we predicted that threatening faces are likely to elicit encoding benefits in WM. Critically, however, threat depends on both the capacities and inclinations of the potential aggressor and the possible responses available to the perceiver. Two experiments demonstrate that participants more efficiently scan memory for angry facial expressions, but only when the faces also bear other cues that are heuristically associated with threat: masculinity in Study 1 and outgroup status in Study 2. Moreover, male participants showed robust speed and accuracy benefits, whereas female participants showed somewhat weaker effects, and only when threat was clearly expressed. Overall results indicate that working memory for faces depends on the accessibility of self-protective goals and on the functional relevance of other social attributes of the face.

Primary biliary cirrhosis (PBC) is a chronic progressive liver disease that often leads to fibrosis, cirrhosis, and end-stage liver disease. The diagnosis is made when there is evidence of cholestasis and reactivity to the antimitochondrial antibody. The etiology of PBC is poorly understood; however, several lines of evidence suggest an environmental factor that triggers a series of immune-mediated inflammatory reactions in the bile ducts in a genetically susceptible individual. Fatigue and pruritus are the most common symptoms of PBC; however, many patients are diagnosed with PBC only based on laboratory abnormalities. The only pharmacological treatment approved for PBC is ursodeoxycholic acid (UDCA). Several controlled studies have shown that UDCA improves liver biochemistries and prolongs transplant-free survival in PBC patients. Nearly 40% of PBC patients do not respond to UDCA, and those patients are at high risk of serious adverse events, such as the development of liver failure. Therefore, newer alternative therapeutic options for PBC are needed. Obeticholic acid is a first-in-class farnesoid X receptor agonist that has been recently evaluated in PBC patients with inadequate response to UDCA, and demonstrated beneficial results in improving liver biochemistries. Several other agents (fibrates and glucocorticoids) have been previously examined in PBC patients with inadequate response to UDCA, and preliminary results showed biochemical improvement. However, large-scale controlled clinical trials are needed to determine the long-term effects of fibrates and glucocorticoids on the clinical outcomes of PBC. Clinical trials of NGM282 (a fibroblast growth factor-19 analog) and Abatacept (a fusion protein composed of the Fc portion of immunoglobulin G1 fused to CTLA4) are currently underway.

Primary emissions from anthropogenic and biogenic sources as well as secondary formation are responsible for the pollution levels of ambient air in major urban areas. These sources release fine particles into the air that negatively impact human health and the environment. Organic molecular markers, which are compounds that are unique to specific PM_2.5 sources, can be utilized to identify the major emission sources in urban areas. In this study, 43 representative PM_2.5 samples, for both daytime and nighttime periods, were built from individual samples collected in an urban site of the Monterrey metropolitan area (MMA) during the spring and fall of 2011 and 2012. The samples were analyzed for organic carbon, elemental carbon, and organic molecular markers. Several diagnostic tools were employed for the preliminary identification of emission sources. Organic compounds for eight compound classes were quantified. The n-alkanoic acids were the most abundant, followed by n-alkanes, wood smoke markers, and levoglucosan/alkenoic acids. Polycyclic aromatic hydrocarbons (PAHs) and hopanes were less abundant. The carbon preference index (0.7–2.6) for n-alkanes indicates a major contribution of anthropogenic and mixed sources during the fall and the spring, respectively. Hopanes levels confirmed the contribution from gasoline and diesel engines. In addition, the contribution of gasoline and diesel vehicle exhaust was confirmed and identified by the PAH concentrations in PM_2.5. Diagnostic ratios of PAHs showed emissions from burning coal, wood, biomass, and other fossil fuels. The total PAHs and elemental carbon were correlated (r² =  0.39–0.70) across the monitoring periods, reinforcing that motor vehicles are the major contributors of PAHs. Cholesterol levels remained constant during the spring and fall, showing evidence of the contribution of meat-cooking operations, while the isolated concentrations of levoglucosan suggested occasional biomass burning events. Finally, source attribution results obtained using the CMB (chemical mass balance) model indicate that emissions from motor vehicle exhausts are the most important, accounting for the 64 % of the PM_2.5, followed by meat-cooking operations with 31 % The vegetative detritus and biomass burning had the smallest contribution (2.2 % of the PM_2.5). To our knowledge, this is only the second study to explore the organic composition and source apportionment of fine organic aerosol based on molecular markers in Mexico and the first for the MMA. Particularly molecular marker were quantified by solvent extraction with dichloromethane, derivatization, and gas chromatography with mass spectrometry (GC/MS).

We show that effective theories of matter that classically violate the null energy condition cannot be minimally coupled to Einstein gravity without being inconsistent with both string theory and black hole thermodynamics. We argue however that they could still be either non-minimally coupled or coupled to higher-curvature theories of gravity.

Human herpesvirus 8 (HHV8) infection leads to potent activation of nuclear factor kappa B (NFκB) in primary and transformed cells. We used recombinant HHV8 (rKSHV.219) expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2α and red fluorescent protein under an early HHV8 lytic gene promoter T1.1 to monitor replication during infection of human foreskin fibroblasts (HF), noting changes in NFκB activity. In primary HF, NFκB levels do not affect the ability of HHV8 to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell-associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFκB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry, was able to partially overcome the deficiency induced by NFκB inhibitors. Our data indicate that in primary cells, NFκB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFκB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.