The Capillary Bed in the Choroid Plexus of the Lateral Ventricles: A Study of Luminal Casts

Micro-angioarchitecture of the choroid plexus of the lateral ventricles is investigated in microcorrosion casts of animal and human preparations studied with the scanning electron microscope. The capillary bed in the diverse regions of the tissue belongs to one of three patterns: (1)-a network of capillary meshes that envelop the larger arteries and veins predominates in the central segment. (2)-in the villous regions a leaf-like organization of sinusoids is found together with (3)-fronds of glomerular formations. Glomeruli are formed when arterial afferents and venous efferents converge in a quasi hilar structure before branching in arterio-venous loops. Nodular thickenings are observed on glomerular capillaries The preparations studied (rat, dog, human) are remarkably similar and differ mostly in degree of occurrence of common architectural patterns. Arterio-venous communications are found at the hilus of human glomerular formations

Methodologies for processing plant material into acceptable food on a small scale

Based on the Controlled Environment Life Support System (CELSS) production of only four crops, wheat, white potatoes, soybeans, and sweet potatoes; a crew size of twelve; a daily planting/harvesting regimen; and zero-gravity conditions, estimates were made on the quantity of food that would need to be grown to provide adequate nutrition; and the corresponding amount of biomass that would result. Projections were made of the various types of products that could be made from these crops, the unit operations that would be involved, and what menu capability these products could provide. Equipment requirements to perform these unit operations were screened to identify commercially available units capable of operating (or being modified to operate) under CELSS/zero-gravity conditions. Concept designs were developed for those equipment needs for which no suitable units were commercially available. Prototypes of selected concept designs were constructed and tested on a laboratory scale, as were selected commercially available units. This report discusses the practical considerations taken into account in the various design alternatives, some of the many product/process factors that relate to equipment development, and automation alternatives. Recommendations are made on both general and specific areas in which it was felt additional investigation would benefit CELSS missions

Lipid bilayer thickness determines cholesterol's location in model membranes

Cholesterol is an essential biomolecule of animal cell membranes, and an important precursor for the biosynthesis of certain hormones and vitamins. It is also thought to play a key role in cell signaling processes associated with functional plasma membrane microdomains (domains enriched in cholesterol), commonly referred to as rafts. In all of these diverse biological phenomena, the transverse location of cholesterol in the membrane is almost certainly an important structural feature. Using a combination of neutron scattering and solid-state 2H NMR, we have determined the location and orientation of cholesterol in phosphatidylcholine (PC) model membranes having fatty acids of different lengths and degrees of unsaturation. The data establish that cholesterol reorients rapidly about the bilayer normal in all the membranes studied, but is tilted and forced to span the bilayer midplane in the very thin bilayers. The possibility that cholesterol lies flat in the middle of bilayers, including those made from PC lipids containing polyunsaturated fatty acids (PUFAs), is ruled out. These results support the notion that hydrophobic thickness is the primary determinant of cholesterol's location in membranes

Neural Network Parameterizations of Electromagnetic Nucleon Form Factors

The electromagnetic nucleon form-factors data are studied with artificial feed forward neural networks. As a result the unbiased model-independent form-factor parametrizations are evaluated together with uncertainties. The Bayesian approach for the neural networks is adapted for chi2 error-like function and applied to the data analysis. The sequence of the feed forward neural networks with one hidden layer of units is considered. The given neural network represents a particular form-factor parametrization. The so-called evidence (the measure of how much the data favor given statistical model) is computed with the Bayesian framework and it is used to determine the best form factor parametrization.Comment: The revised version is divided into 4 sections. The discussion of the prior assumptions is added. The manuscript contains 4 new figures and 2 new tables (32 pages, 15 figures, 2 tables

Attitudinal and socio-structural determinants of cervical cancer screening and HPV vaccination uptake: a quantitative multivariate analysis

Aim: The introduction of the human papillomavirus (HPV) vaccine enables for the first time in the history of cancer prevention the possibility of combating the major cause of a cancer even before its onset. The secondary prevention measure of cervical cancer screening has thus been complemented by a primary prevention measure. The aim of this study is to analyse the determinants of uptake of preventive measures against cervical cancer as a basis for comparing the determinants of screening attendance with those of HPV vaccination attendance. Subject and methods: A population-based representative survey comprising 760 randomly selected women aged 14 to 65 was performed in the German federal state of Mecklenburg-Western Pomerania. Prevention behaviour, attitudes towards cervical cancer screening and HPV vaccination, and knowledge about cervical cancer and HPV were investigated by means of a structured questionnaire. Descriptive analyses and multivariate logistic regression analyses were conducted to identify the determinants of screening and HPV vaccine uptake. Results: Attendance both at screening and at HPV vaccination was best predicted by attitudinal factors. Positive connotations of cancer prevention measures and utility expectations, fear of cancer and high subjective risk perception were conducive to attendance at screening and HPV vaccination. Screening attendance was less regular among women of lower socioeconomic status. In contrast, HPV vaccination uptake was higher for young women with lower educational attainment and lower social class. Knowledge did not impact prevention behaviour significantly. There is no trade-off between screening and vaccination attendance; the vast majority of respondents was aware of the necessity of regular screening attendance even when vaccinated against HPV. Conclusions: Uptake rates for existing primary and secondary prevention measures against cervical cancer can be enhanced by fostering perceptions of utility and positive connotations of regular screening and becoming vaccinated against HPV. Elderly women in particular should be encouraged to attend screening by means of a recall system. Given the low overall level of knowledge about cervical cancer and its risk factors, there is a need for education about the necessity and utility of prevention to reach women of all social classes

Fast fluorescence techniques for crystallography beamlines

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86817/1/S0021889811016748.pd

A Novel Mechanism of Programmed Cell Death in Bacteria by Toxin–Antitoxin Systems Corrupts Peptidoglycan Synthesis

Most genomes of bacteria contain toxin–antitoxin (TA) systems. These gene systems encode a toxic protein and its cognate antitoxin. Upon antitoxin degradation, the toxin induces cell stasis or death. TA systems have been linked with numerous functions, including growth modulation, genome maintenance, and stress response. Members of the epsilon/zeta TA family are found throughout the genomes of pathogenic bacteria and were shown not only to stabilize resistance plasmids but also to promote virulence. The broad distribution of epsilon/zeta systems implies that zeta toxins utilize a ubiquitous bacteriotoxic mechanism. However, whereas all other TA families known to date poison macromolecules involved in translation or replication, the target of zeta toxins remained inscrutable. We used in vivo techniques such as microscropy and permeability assays to show that pneumococcal zeta toxin PezT impairs cell wall synthesis and triggers autolysis in Escherichia coli. Subsequently, we demonstrated in vitro that zeta toxins in general phosphorylate the ubiquitous peptidoglycan precursor uridine diphosphate-N-acetylglucosamine (UNAG) and that this activity is counteracted by binding of antitoxin. After identification of the product we verified the kinase activity in vivo by analyzing metabolite extracts of cells poisoned by PezT using high pressure liquid chromatograpy (HPLC). We further show that phosphorylated UNAG inhibitis MurA, the enzyme catalyzing the initial step in bacterial peptidoglycan biosynthesis. Additionally, we provide what is to our knowledge the first crystal structure of a zeta toxin bound to its substrate. We show that zeta toxins are novel kinases that poison bacteria through global inhibition of peptidoglycan synthesis. This provides a fundamental understanding of how epsilon/zeta TA systems stabilize mobile genetic elements. Additionally, our results imply a mechanism that connects activity of zeta toxin PezT to virulence of pneumococcal infections. Finally, we discuss how phosphorylated UNAG likely poisons additional pathways of bacterial cell wall synthesis, making it an attractive lead compound for development of new antibiotics

Identification of IKr Kinetics and Drug Binding in Native Myocytes

Determining the effect of a compound on IKr is a standard screen for drug safety. Often the effect is described using a single IC50 value, which is unable to capture complex effects of a drug. Using verapamil as an example, we present a method for using recordings from native myocytes at several drug doses along with qualitative features of IKr from published studies of HERG current to estimate parameters in a mathematical model of the drug effect on IKr. IKr was recorded from canine left ventricular myocytes using ruptured patch techniques. A voltage command protocol was used to record tail currents at voltages from −70 to −20 mV, following activating pulses over a wide range of voltages and pulse durations. Model equations were taken from a published IKr Markov model and the drug was modeled as binding to the open state. Parameters were estimated using a combined global and local optimization algorithm based on collected data with two additional constraints on IKrI–V relation and IKr inactivation. The method produced models that quantitatively reproduce both the control IKr kinetics and dose dependent changes in the current. In addition, the model exhibited use and rate dependence. The results suggest that: (1) the technique proposed here has the practical potential to develop data-driven models that quantitatively reproduce channel behavior in native myocytes; (2) the method can capture important drug effects that cannot be reproduced by the IC50 method. Although the method was developed for IKr, the same strategy can be applied to other ion channels, once appropriate channel-specific voltage protocols and qualitative features are identified

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p \u3c 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p \u3e 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders