Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p

Effects of cage mesh on pointing: hand shapes in chimpanzees (Pan troglodytes)

It has been speculated that cage mesh exerts a shaping influence on reaching behavior by captive apes, which is then misconstrued as pointing by human observers. Although this notion is clearly falsified by the pointing of captive language-trained apes who point in the absence of intervening cage meshnevertheless, the degree to which cage mesh might influence pointing hand shapes by captive great apes in other housing environments remains relatively unexplored. We examined 259 pointing gestures displayed in archival footage from over 18 hours of observation by three non-language-trained chimpanzees housed at a biomedical research center. We coded points in relation to how close to the boundaries of the diamond-shaped cage mesh their points were displayed. We found that points with the whole hand were significantly more likely to be displayed away from the mesh boundaries, relative to points with the index finger or other single-digit points. However, points of each hand shape were displayed at each location, demonstrating that these physical parameters do not fully account for the number of fingers extended while pointing by chimpanzees

Enhanced interpretation of newborn screening results without analyte cutoff values

A collaboration among 157 newborn screening programs in 47 countries has lead to the creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with 57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114 cutoff target ranges. Objective: To improve quality and performance with an evidence-based approach, multivariate pattern recognition software has been developed to aid in the interpretation of complex analyte profiles. The software generates tools that convert multiple clinically significant results into a single numerical score based on overlap between normal and disease ranges, penetration within the disease range, differences between specific conditions, and weighted correction factors. Design: Eighty-five on-line tools target either a single condition or the differential diagnosis between two or more conditions. Scores are expressed as a numerical value and as the percentile rank among all cases with the condition chosen as primary target, and are compared to interpretation guidelines. Tools are updated automatically after any new data submission (2009- 2011: 5.2 new cases added per day on average). Main outcome measures: Retrospective evaluation of past cases suggest that these tools could have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid oxidation disorders, and could have prevented 88% of false negative events caused by cutoff 7 values set inappropriately. In Minnesota, their prospective application has been a major contributing factor to the sustained achievement of a false positive rate below 0.1% and a positive predictive value above 60%. Conclusions: Application of this computational approach to raw data could make cutoff values for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine. Abstract wor

Experimental Conversations: Sign Language Studies with Chimpanzees

Sign language studies of chimpanzees are a tool for studying the continuity between human behavior and behavior of other animals and between verbal behavior and other intelligent behavior. Cross-fostered chimpanzees paralleled children in their acquisition and use of signs and phrases. These procedures occurred under rigorous and systematic record keeping and experimental paradigms. The study of Wh-questions and the use of remote videotaping (RVT) are examples of experimental procedures. These revealed chimpanzee-to-chimpanzee signing and private signing. Face-to-face interactions between the chimpanzees and an interlocutor who presented various systematic probes is another experimental procedure. The chimpanzees adjusted to the interlocutor with revisions, new signs, or no response when appropriate. The hallmark of the sign language studies is that caregivers treated the chimpanzees as conversational partners socially motivated rather than experimental subjects bribed or forced into participation. These findings confirm continuity with differences of degree among species

Newborn screening for inborn errors of metabolism and endocrinopathies: an update

Newborn screening for inborn errors of metabolism and endocrinopathies has expanded during the last two decades, mainly owing to the introduction of new technologies such as tandem mass spectrometry and DNA analysis. However, every expansion of the screening panel requires critical review, discussion, and pilot studies. Different legal regulations and ethical concerns may lead to different decisions. Without claiming to be comprehensive, this review tries to give an overview of newborn screening, including its main problems and target diseases