Unique Education and Workforce Development for NASA Engineers

NASA engineers are some of the world's best-educated graduates, responsible for technically complex, highly significant scientific programs. Even though these professionals are highly proficient in traditional analytical competencies, there is a unique opportunity to offer continuing education that further enhances their overall scientific minds. With a goal of maintaining the Agency's passionate, "best in class" engineering workforce, the NASA Academy of Program/Project & Engineering Leadership (APPEL) provides educational resources encouraging foundational learning, professional development, and knowledge sharing. NASA APPEL is currently partnering with the scientific community's most respected subject matter experts to expand its engineering curriculum beyond the analytics and specialized subsystems in the areas of: understanding NASA's overall vision and its fundamental basis, and the Agency initiatives supporting them; sharing NASA's vast reservoir of engineering experience, wisdom, and lessons learned; and innovatively designing hardware for manufacturability, assembly, and servicing. It takes collaboration and innovation to educate an organization that possesses such a rich and important history~and a future that is of great global interest. NASA APPEL strives to intellectually nurture the Agency's technical professionals, build its capacity for future performance, and exemplify its core values~alJ to better enable NASA to meet its strategic vision~and beyond

Reproductive Morphology of Male Black Perch (Embiotoca jacksoni)

Black perch (Embiotoca jacksoni) are a common southern California fish that exhibits internal fertilization. During copulation, males transfer a spermatozeugmata to the female via an intromittent organ. Relatively little is known about the reproductive morphology of male black perch and the spermatozeugmata. The objective of our study was to describe the development of spermatocytes and the spermatozeugmata. We also used histology to examine the anal fin and describe the tissues of the intromittent organs. Black perch \u3c 90 mm SL had testes that were composed of spermatocytes at all developmental stages. All stages of spermatocytes in addition to spermatozeugmata were present in males ³ 90 mm SL. On both sides of the anal fin at the anterior end, an intromittent organ was housed in a sheath composed of smooth muscle. Our research note is the first to document the formation of black perch spermatozeugmata within the testis. We also characterized the tissues of the intromittent organs and its muscular sheath which reside on an unmodified anal fin. The copulatory structures of embiotocid species have not been fully investigated, thus our work contributes to understanding the reproductive biology of surfperches

NfL as a biomarker for neurodegeneration and survival in Parkinson disease

OBJECTIVE: To determine if Neurofilament Light chain protein in cerebrospinal fluid (cNfL); a sensitive biomarker of neuroaxonal damage, reflects disease severity or can predict survival in Parkinson's disease (PD). METHODS: We investigated if disease severity, phenotype or survival in patients with new-onset PD correlates with cNfL concentrations around the time of diagnosis in the population-based NYPUM study cohort (n = 99). A second, larger new-onset PD cohort (n = 194) was used for independent validation. Association of brain pathology with the cNfL concentration was examined using striatal dopamine transporter imaging and repeated diffusion tensor imaging, at baseline, 1 and 3 years. RESULTS: Higher cNfL in the early phase of PD was associated with greater severity of all cardinal motor symptoms except tremor, in both cohorts, and with shorter survival and impaired olfaction. cNfL concentrations above the median of 903 ng/L conferred an overall 5.8 times increased hazard of death, during follow-up. After adjustment for age and sex, higher cNfL correlated with striatal dopamine transporter uptake deficits and lower fractional anisotropy in diffusion tensor imaging of several axonal tracts. CONCLUSIONS: cNfL shows usefulness as a biomarker of disease severity and to predict survival in PD. The present results indicate that the cNfL concentration reflects the intensity of the neurodegenerative process, which could be of importance in future clinical trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with PD, cNFL concentrations are associated with more severe disease and shorter survival

Immunodepletion in xenotransplantation

Xenograft transplantation is perhaps the most immunologically difficult problem in transplantation today. An overwhelming hyperacute rejection reaction (HAR) occurs within minutes of organ implantation. Preformed antibodies are thought to initiate this process. We used a pig-to-dog renal xenograft transplant model and investigated methods of decreasing the severity of hyperacute rejection. Female pigs weighing 15-20 kg were used as donors. Recipients were mongrel dogs weighing 15-25 kg. Experimental dogs were all given a number of treatments of IgG depletion using an antibody removal system (Dupont-Excorim). This machine immunoadsorbs plasma against a column containing immobilized staphylococcal protein A, which is known to bind the IgG Fc receptor. An 84% reduction in the IgG levels and a 71% reduction in IgM levels was achieved. Postoperative assessment was made of urine output, time to onset of HAR, and histopathological examination of the rejected kidneys. Although cross-matches between donor lymphocytes and recipient sera remained strongly positive in the treated dogs, there was a two- to fourfold reduction in the titers. The time to onset of HAR was prolonged in the experimental group, and the urine output was increased slightly. The histopathologic changes in the experimental group generally showed signs of HAR, but of less intensity than in the nonimmunodepleted control group. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

PHYSIOLOGY AND MANAGEMENT Bovine Lactoferrin Receptors in Staphylococcus aureus Isolated from Bovine Mastitis

ABSTRACT A total of 103 Staphylococcus a w e w strains isolated from bovine mastitis were tested for bovine lactoferrin binding in a 1251-labeled protein binding assay. More than 85% of the strains demonstrated high to moderate and a few showed little or no binding. Bovine lactoferrin binding to S. aureus cells was high when grown on blood, nutrient, or proteose-peptone agar, but the binding capacity was low with cells grown on salt rich media, in skim milk, or in broth. The kinetics of 1251-labeled bovine lactoferrin binding required approximately 90 min for complete saturation with optimal interaction in the pH range 4.0 to 7.0. The lactoferrin-staphylococci interaction was specific with a high affinity (association constant, K, 14 x 106 L/mol). Scatchard plot analysis estimated the number of binding sites per cell at 7200 on strain SA-340. Unlabeled bovine lactoferrin effectively displaced the binding of the labeled ligand to strain SA-340 in a dosedependent manner. Abbreviation key: bLf = bovine lactoferrin, hLf = human lactoferrin, HRPO = horseradish peroxidase, Lf = lactoferrin, PBS = phosphatebuffered saline, PMN = polymorphonuclear leukocytes

Gender differences in Parkinson's disease: A clinical perspective

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta‐analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor‐dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross‐sectional. Good‐quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD

Deep Mining of Oxysterols and Cholestenoic Acids in Human Plasma and Cerebrospinal Fluid: Quantification using Isotope Dilution Mass Spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction Are Altered in Parkinson's Disease and Related Disorders

Background: Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects. Objective: To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders. Methods: Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n1 = 51, n2 = 101), corticobasal degeneration (CBD) (n1 = 11, n2 = 3), progressive supranuclear palsy (PSP) (n1 = 22, n2 = 21), multiple system atrophy (MSA) (n1 = 31, n2 = 26), and healthy control (HC) (n1 = 48, n2 = 30) participants, as well as Alzheimer's disease (AD) (n2 = 23) patients in the second cohort. Results: Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021). Conclusions: These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society