Lipid peroxidation biomarkers for evaluating oxidative stress in equine neuroaxonal dystrophy.

BackgroundEquine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on an α-tocopherol (α-TOH) deficient diet. Currently no antemortem diagnostic test for eNAD/EDM is available.HypothesisBecause α-TOH deficiency is associated with increased lipid peroxidation, it was hypothesized that F2 -isoprostanes (F2 IsoP), F4 -neuroprostanes (F4 NP) and oxysterols derived from free radical oxidation would be increased in the cerebrospinal fluid (CSF) and neural tissue of eNAD/EDM affected horses and could serve as potential biomarkers for disease.AnimalsIsoprostane Study A: 14 Quarter horse foals (10 healthy foals and 4 eNAD/EDM affected foals) at 1 and 6 months of age. Isoprostane Study B: 17 eNAD/EDM affected and 10 unaffected horses ≥ 1-4 years of age. Oxysterol study: eNAD/EDM affected (n = 14, serum; n = 11, CSF; n = 10, spinal cord [SC]) and unaffected horses 1-4 years of age (n = 12, serum; n = 10, CSF; n = 7, SC).ProceduresCerebrospinal fluid [F2 IsoP] and [F4 NP] were assessed using gas chromatography-negative ion chemical ionization mass spectrometry. Serum, CSF, and cervical SC [oxysterols] were quantified using high performance liquid chromatography mass spectrometry. Results were compared with respective α-TOH concentrations.ResultsSpinal cord [7-ketocholesterol], [7-hydroxycholesterol], and [7-keto-27-hydrocholesterol] were higher in eNAD/EDM horses whereas [24-ketocholesterol] was lower. No significant difference was found in CSF [F2 IsoP] and [F4 NP], serum [oxysterols] and CSF [oxysterols] between eNAD/EDM affected and unaffected horses. No correlation was found between [F2 IsoP], [F4 NP], or [oxysterols] and respective [α-TOH].Conclusions and clinical importanceIn the SC, targeted markers of cholesterol oxidation were significantly increased in horses with eNAD/EDM

Identification of Mechanism-Based Inactivation in P450-Catalyzed Cyclopropanation Facilitates Engineering of Improved Enzymes

Following the recent discovery that heme proteins can catalyze the cyclopropanation of styrenyl olefins with high efficiency and selectivity, interest in developing new enzymes for a variety of non-natural carbene transfer reactions has burgeoned. The fact that diazo compounds and other carbene precursors are known mechanism-based inhibitors of P450s, however, led us to investigate if they also interfere with this new enzyme function. We present evidence for two inactivation pathways that are operative during cytochrome P450-catalyzed cyclopropanation. Using a combination of UV–vis, mass spectrometry, and proteomic analyses, we show that the heme cofactor and several nucleophilic side chains undergo covalent modification by ethyl diazoacetate (EDA). Substitution of two of the affected residues with less-nucleophilic amino acids led to a more than twofold improvement in cyclopropanation performance (total TTN). Elucidating the inactivation pathways of heme protein-based carbene transfer catalysts should aid in the optimization of this new biocatalytic function

CHARACTERIZING FORAGING PATTERNS AMONG CATTLE AND BONDED AND NON-BONDED SMALL RUMINANTS USING SPATIAL POINT PROCESS TECHNIQUES

This paper uses the technique of spatial point processes to describe the spatial patterns of freeranging cattle and small ruminants. Two mixed-species livestock groups were monitored while foraging on 410 ha of brush-infested Southern New Mexico rangeland during July and August 1988. The groups consisted of crossbred Bos taurus and Bos indicus beef cattle with white-faced sheep (Ovis aries) and mohair goats (Capra hircus). The bonded group consisted of small ruminants that had their behaviours modified through socialization with cattle to form a ‘flerd’ in which small ruminants consistently remained near cattle. Small ruminants in the non-bonded group had not been socialized with cattle. A subset of animal location data measured during the morning and afternoon over five days for both the bonded and non-bonded groups was analyzed for spatial patterns. Only data for five morning periods (7:00-8:00 a.m.) are reported because morning and afternoon spatial patterns were similar. Observed nearest neighbor distances, mean number of small ruminant near an arbitrary cow, and point-to-animal distances were compared to Monte Carlo simulations of independently and uniformly distributed animal locations. Bonded and non-bonded groups were also compared. Results suggested bonded and non-bonded groups were similar in spatial patterns of intra-specific distances for both cattle and small ruminants. However, bonding changed the repulsive relationship observed between cattle and non-bonded small ruminants stocked together to one of inter-specific attraction. Bonded small ruminants remained close to and formed inter-specific clusters with cattle. In addition, the mean number of bonded small ruminants near an arbitrary cow was consistently higher than for non-bonded small ruminants. Finally, the spatial pattern of cattle across the paddock did not differ between bonded and non-bonded groups, while bonded small ruminants tended to disperse slightly more uniformly across the paddock than did non-bonded small ruminants. These findings indicate the usefulness of spatial point processes techniques to analyze such animal location data, substantiate on a larger scale conclusions of previous, replicated studies about the effect of bonding small ruminants to cattle, and suggest utilization of paddock landscapes may be positively influenced using flerds compared to flocks and herds

Embracing open innovation to acquire external ideas and technologies and to transfer internal ideas and technologies outside

The objective of this dissertation is to increase understanding of how organizations can embrace open innovation in order to acquire external ideas and technologies from outside the organization, and to transfer internal ideas and technologies to outside the organization. The objective encompasses six sub-objectives, each addressed in one or more substudies. Altogether, the dissertation consists of nine substudies and a compendium summarizing the substudies. An extensive literature review was conducted on open innovation and crowdsourcing literature (substudies 1–4). In the subsequent empirical substudies, both qualitative research methods (substudies 5–7) and quantitative research methods (substudies 8–9) were applied. The four literature review substudies provided insights on the body of knowledge on open innovation and crowdsourcing. These substudies unveiled most of the influential articles, authors, and journals of open innovation and crowdsourcing disciplines. Moreover, they identified research gaps in the current literature. The empirical substudies offer several insightful findings. Substudy 5 shows how non-core ideas and technologies of a large firm can become valuable, especially for small firms. Intermediary platforms can find solutions to many pressing problems of large organizations by engaging renowned scientists from all over world (substudy 6). Intermediary platforms can also bring breakthrough innovations with novel mechanisms (substudy 7). Large firms are not only able to garner ideas by engaging their customers through crowdsourcing but they can also build long-lasting relations with their customers (substudies 8 and 9). Embracing open innovation brings challenges for firms too. Firms need to change their organizational structures in order to be able to fully benefit from open innovation. When crowdsourcing is successful, it produces a very large number of new ideas. This has the consequence that firms need to allocate a significant amount of resources in order to identify the most promising ideas. In an idea contest, customarily, only one or a few best ideas are rewarded (substudy 7). Sometimes, no reward is provided for the selected idea (substudies 8 and 9). Most of the ideas that are received are not implemented in practice

A Multicenter Evaluation of Pediatric Emergency Department Injury Visits during the COVID-19 Pandemic

BACKGROUND: Injuries, the leading cause of death in children 1-17 years old, are often preventable. Injury patterns are impacted by changes in the child\u27s environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. METHODS: This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children \u3c 18 years old. Injury was defined by at least one International Classification of Disease-10th revision (ICD-10) code for bodily injury (S00-T78). The main study outcomes were total and proportion of PED injury-related visits compared to all visits in March through December 2020 and to the same months in 2019. Weekly injury visits as a percentage of total PED visits were calculated for all weeks between January 2019 and December 2020. RESULTS: The study included 741,418 PED visits for injuries pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020). Overall PED visits from all causes decreased 27.4% in March to December 2020 compared to the same time frame in 2019; however, the proportion of injury-related PED visits in 2020 increased by 37.7%. In 2020, injured children were younger (median age 6.31 years vs 7.31 in 2019), more commonly White (54% vs 50%, p \u3c 0.001), non-Hispanic (72% vs 69%, p \u3c 0.001) and had private insurance (35% vs 32%, p \u3c 0.001). Injury hospitalizations increased 2.2% (p \u3c 0.001) and deaths increased 0.03% (p \u3c 0.001) in 2020 compared to 2019. Mean injury severity score increased (2.2 to 2.4, p \u3c 0.001) between 2019 and 2020. Injuries declined for struck by/against (- 4.9%) and overexertion (- 1.2%) mechanisms. Injuries proportionally increased for pedal cycles (2.8%), cut/pierce (1.5%), motor vehicle occupant (0.9%), other transportation (0.6%), fire/burn (0.5%) and firearms (0.3%) compared to all injuries in 2020 versus 2019. CONCLUSIONS: The proportion of PED injury-related visits in March through December 2020 increased compared to the same months in 2019. Racial and payor differences were noted. Mechanisms of injury seen in the PED during 2020 changed compared to 2019, and this can inform injury prevention initiatives

Properties, production, and applications of camelid single-domain antibody fragments

Camelids produce functional antibodies devoid of light chains of which the single N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments (VHHs or Nanobodies®) have several advantages for biotechnological applications. They are well expressed in microorganisms and have a high stability and solubility. Furthermore, they are well suited for construction of larger molecules and selection systems such as phage, yeast, or ribosome display. This minireview offers an overview of (1) their properties as compared to conventional antibodies, (2) their production in microorganisms, with a focus on yeasts, and (3) their therapeutic applications

Search for gravitational waves associated with fast radio bursts detected by CHIME/FRB during the LIGO-Virgo observing Run O3a

We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 1051–1057 erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB

Exomorfología y anatomía de órganos vegetativos aéreos en especies de Flourensia DC. (Asteraceae) con importancia fitoquímica

El género Flourensia DC. es americano y comprende 32 especies. Son arbustos resinosos utilizados en medicina popular; poseen un potencial valor económico, por lo que, en algunas especies representantes, se han caracterizado sus compuestos químicos y determinado algunos posibles usos. En el presente trabajo, se estudió la exomorfología y anatomía de órganos vegetativos de F. hirta S. F. Blake, F. leptopoda S. F. Blake, F. niederleinii S. F. Blake y F. tortuosa Griseb., especies endémicas del centro de Argentina. Se observó que todas son similares en cuanto a la anatomía de hoja y tallo. En cuanto al estudio de la epidermis foliar, se concluye que es posible diferenciar las especies teniendo en cuenta la frecuencia estomática y la presencia de tricomas. Finalmente, las diferencias más notables se encontraron en la exomorfología foliar ya que se observó una gran variación en cuanto a la forma de las hojas y tamaño de las láminas y pecíolos. Con respecto a las estructuras secretoras, se encontraron tricomas y conductos secretores esquizógenos en las hojas y los tallos de todas las especies, las cuales serían responsables de la producción y secreción de las resinas.The genus Flourensia DC. is American and comprises 32 species. They are resiniferous shrubs used in folk medicine. As they have potential economic value, its chemical compounds have been characterized and some possible uses identified. In this work, the exomorphology and anatomy of vegetative organs of F. hirta S. F. Blake, F. leptopoda S. F. Blake, F. niederleinii S. F. Blake and F. tortuosa Griseb., endemic species from central Argentina, have been studied. All species are similar in leaf and stem anatomy. Regarding the epidermis, it is possible to differentiate the species according to the stomatal frequency and the presence of trichomes. Finally, the most remarkable differences were found in leaf exomorphology, since there was a large variation in shape and size of blades and petioles. Concerning the secretory structures, trichomes and secretory ducts were found in the leaves and stems of all species, which would be responsible for the production and secretion of the resins