SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.

Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1-7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin-Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis

Automated Data Management Information System (ADMIS)

ADMIS stores and controls data and documents associated with manned space flight effort. System contains all data oriented toward a specific document; it is primary source of reports generated by the system. Each group of records is composed of one document record, one distribution record for each recipient of the document, and one summary record

Modeling photodetachment from HO2− using the pd case of the generalized mixed character molecular orbital model

Using the generalized model for photodetachment of electrons from mixed-character molecular orbitals, we gain insight into the nature of the HOMO of HO$_{2}$$^{-}$ by treating it as a coherent superpostion of one p- and one d-type atomic orbital. Fitting the pd model function to the ab initio calculated HOMO of HO$_{2}$$^{-}$ yields a fractional d-character, $\gamma$$_{p}$, of 0.979. The modeled curve of the anisotropy parameter, $\beta$, as a function of electron kinetic energy for a pd-type mixed character orbital is matched to the experimental data

Vesicle trafficking and pathways to neurodegeneration

Neurodegenerative diseases, encompassing a diverse range of inherited and sporadic disorders characterised by progressive loss of relatively discrete neuronal populations, are a significant and increasing challenge to human health and the global economy [1]. Despite significant advances in our understanding of the underlying ætiology of diseases such as Alzheimer’s, Parkinson’s and Huntington’s, and intense efforts targeting the development of disease-modifying therapies for these disorders, for the majority of people living with neurodegenerative conditions the prognosis remains poor [2,3,4]. Improving our knowledge of the underlying causes of neuronal loss in these disorders with the goal of developing novel disease-modifying therapies is thus a top priority for research, patient and care-giver communities

PHOTOELECTRON IMAGING SPECTROSCOPY AS A WINDOW TO UNEXPECTED MOLECULES

Targeting an anion with the formula CH$_{3}$O$_{3}$ for exploration with photoelectron imaging spectroscopy, we determine its identity to be dihydroxymethanolate, an anion largely absent in the literature, and the conjugate base of the hypothetical species orthoformic acid. Comparing the observed photoelectron spectrum to CCSD-EOM-IP and CCSD-EOM-SF calculations completed in QChem and Franck-Condon overlap simulations in PESCAL, we are able to determine with confidence the connectivity of the atoms in this molecule

THE CURIOUS(ER) CASE OF MASS 63: A THRILLING AND CONFUSING SEQUEL

Produced in a reaction or interaction either between methanol and methoxide or methoxide and oxygen, an unexpected and difficult to identify species has appeared in our mass spectrum. We seek to narrow its molecular formula to one of \chem{CH_3 O_3} or \chem{C_2 H_7 O_2} using fully deuterated methanol as a precursor to separate the two formulas by mass, and to further use the photoelectron spectrum and a fragmentation spectrum of the fully deuterated species to most accurately determine the molecular identity and completely assign its photoelectron spectrum

Temperature Dependence Of The Electronic Absorption Spectrum Of NO2

The nitrogen dioxide (NO2) radical is composed of the two most abundant elements in the atmosphere, where it can be formed in a variety of ways including combustion, detonation of energetic materials, and lightning. Relevant also to smog and ozone cycles, together these processes span a wide range of temperatures. Remarkably, high-resolution NO2 electronic absorption spectra have only been reported in a narrow range below about 300 K. Previously, we reported [ J. Phys. Chem. A 2021, 125, 5519−5533 ] the construction of quasi-diabatic potential energy surfaces (PESs) for the lowest four electronic states (X̃, Ã, B̃, and C̃) of NO2. In addition to three-dimensional PESs based on explicitly correlated MRCI(Q)-F12/VTZ-F12 ab initio data, the geometry dependence of each component of the dipoles and transition dipoles was also mapped into fitted surfaces. The multiconfigurational time-dependent Hartree (MCTDH) method was then used to compute the 0 K electronic absorption spectrum (from the ground rovibrational initial state) employing those energy and transition dipole surfaces. Here, in an extension of that work, we report an investigation into the effects of elevated temperature on the spectrum, considering the effects of the population of rotationally and vibrationally excited initial states. The calculations are complemented by new experimental measurements. Spectral contributions from hundreds of rotational states up to N = 20 and from 200 individually-characterized vibrational states were computed. A spectral simulation tool was developed that enables modeling the spectrum at various temperatures─by weighting individual spectral contributions via the partition function, or for pure excited initial states, which can be probed via transient absorption spectroscopy. We validate these results against experimental absorption spectroscopy data at high temperatures, as well as via a new measurement from the (1,0,1) initial vibrational state

Geriatric Hip Fracture Quality Initiative

Introduction: Multiple studies demonstrate increased morbidity, mortality, and loss of independence after hip fractures in geriatric patients. The 1-year mortality rate after a hip fracture has been estimated at anywhere from 14% to 58%. Hip fractures are one of the most common injuries evaluated by the UNM Orthopedic department. Geriatric hip fracture protocols have shown improved outcomes at many other centers with regard to improved functionality and decreased morbidity. The goal of this initiative is to improve outcomes with regard to length of hospital stay, functionality after surgery, and as a result, decreased morbidity and mortality. Materials/methods: All deaths in the orthopedic department were reviewed and analyzed from June 2009 to July 2019. Deaths were identified from morbidity and mortality submissions and NSQIP data. The geriatric hip fracture protocol was developed and implemented in Fall 2019, with non-critical care patients being primarily admitted to orthopedics, with hospitalist co-management. Specific post-operative and pain order sets were developed for efficiency and improved standard of care. Results: Early results of the newly developed geriatric hip fracture protocol demonstrate decreased length of stay in the hospital and earlier time to surgical intervention. It is too early to determine if morbidity and mortality has seen any decrease, however this can be anticipated with earlier time to surgery and decreased time in the hospital. Conclusions: We identified a need and successfully developed an initiative to improve care for geriatric patients with hip fractures. Implementation of this protocol decreased length of hospital stay as well as time to surgery. The analysis of the effect of this protocol on overall morbidity and mortality is ongoing

Analysis of morbid events and risk factors for death after cardiac transplantation

AbstractRisk factors for death after cardiac transplantation performed at the University of Alabana at Birmingham from January 1981 to July 1985 included (by multivariate analysis) higher calculated preoperative pulmonary vascular resistance (early and constant phases), murphology of cardiomyopathy (versus ischemic heart disease) (constant phase only) and black race (constant phase). overall actuarial survival was 71% at 1 year and 48% at 3 years (including azalhioprine and cyclosporine eras). The hazard function for death was highest immediately after operation and declined rapidly thereafter, merging with a constant phase of risk at about 3 months.The most favorable group for long-term survival was the group of white patients with ischemic heart disease and low pulmonary vascular resistance. When such patients had a pulmonary vascular resistance < 3 units m2, the 3 year survival rate exceeded 85%; The most common causes of death were acute rejection (24%) and infection (17%) The risk of infection remained highest during the first several months after any period of augmented immunosuppression

Fate of the esophagogastric anastomosis

ObjectiveThe study objective was to evaluate histopathology of the esophagogastric anastomosis after esophagectomy, determine time trends of histologic changes, and identify factors influencing those findings.MethodsA total of 231 patients underwent 468 upper gastrointestinal endoscopies with anastomotic biopsy a median of 3.5 years after esophagectomy. Mean age was 59 ± 12 years, 74% (171) were male, and 96% (222) were white. Seventy-eight percent (179) had esophagectomy for cancer, 13% (30) had chemoradiotherapy, and 13% (30) had prior esophageal surgery. The anastomosis was 20 ± 2.0 cm from the incisors. Anti-reflux medications were used in 59% of patients (276/468) at esophagoscopy. Histopathology was graded as normal (0), consistent with reflux (1), cardia mucosa (2), intestinal metaplasia (3), and dysplasia (4). Repeated-measures nonlinear time-trend analysis and multivariable analyses were used.ResultsGrades 0 and 1 were constant, 5% and 92% at 10 years, respectively. Anti-reflux medication, induction therapy, and higher anastomosis were predictive of less grade 1 histopathology. Grades 2 and 3 increased with time: 12% and 33% at 5 years and 4% and 16% at 10 years, respectively. No variable was predictive of grade 2 or 3 (P > .15) except passage of time. No patient’s condition progressed to dysplasia or cancer.ConclusionsThe esophagogastric anastomosis is subject to gastroesophageal reflux. To minimize histopathologic changes of reflux, the anastomosis should be constructed as high as possible (closer to incisors) and anti-reflux medications prescribed. Surveillance endoscopy, if performed, will document a time-related progression of reflux-related histopathologic changes. However, during surveillance, intestinal metaplasia is uncommon and progression to cancer rare