New Directions in Dietary Restriction: Remembering Edward Masoro

In 1935, Clive McCay reported that severe restriction of food increased the lifespan of male rats. In the following four decades, several laboratories replicated this observation with less sever restrictions, which will be referred to as dietary restriction (DR). However, there were concerns even in the aging community in the 1970s as to whether DR increased lifespan by retarding aging. It was the research of two former Kleemeier Awardees, Edward Masoro and Roy Walford, that conclusively demonstrated in the 1980s that DR retarded aging resulting in improved healthspan and reduced pathology. Ed Masoro’s research was focused on lipid metabolism when he was invited to attend a workshop on metabolism and aging in 1969. His interest in aging was piqued such that the more he learned about aging, the more interested he became. In a subsequent workshop in 1973, Ed heard Morris Ross describe his research on restricting food intake on cancer and longevity. Ed was impressed that a relatively simple manipulation had such dramatic effects, and he decided to focus his research on DR. After an extensive review of the DR literature up to the 1970s, Ed established the 40% restriction paradigm, which is used in almost all DR studies to date. Ed’s group was the first to study aging and DR under barrier conditions which he established at San Antonio. Over the next two decades, Ed would direct a Program Project that showed DR had a dramatic effect on most age-related pathologies and improved many physiological functions. Studying the restriction of fat, protein, micronutrients, Ed came to the conclusion that total calories consumed was a key factor in the effect of DR on longevity. His group was the first to show that DR significantly reduced circulating levels of glucose and insulin, which was subsequently shown to occur because of increased insulin sensitivity and is now recognized as a hallmark of DR and potentially important in the anti-aging action of DR. Ed was chair of the Biological Sciences Section of GSA in 1979 and President in 1995. This session is dedicated to Edward Masoro who passed away on July 11, 2020 at the age or 95.Dr. Masoro was president in 1995 and BS chair in 1979, Clive McCay was President in 1949.

Modeling Alternate Conformations with Alphafold2 via Modification of the Multiple Sequence Alignment

The unprecedented performance of Deepmind's Alphafold2 in predicting protein structure in CASP XIV and the creation of a database of structures for multiple proteomes is reshaping structural biology. Moreover, the availability of Alphafold2's architecture and code has stimulated a number of questions on how to harness the capabilities of this remarkable tool. A question of central importance is whether Alphafold2's architecture is amenable to predict the intrinsic conformational heterogeneity of proteins. A general approach presented here builds on a simple manipulation of the multiple sequence alignment, via in silico mutagenesis, and subsequent modeling by Alphafold2. The approach is based in the concept that the multiple sequence alignment encodes for the structural heterogeneity, thus its rational manipulation will enable Alphafold2 to sample alternate conformations and potentially structural alterations due to point mutations. This modeling pipeline is benchmarked against canonical examples of protein conformational flexibility and applied to interrogate the conformational landscape of membrane proteins. This work broadens the applicability of Alphafold2 by generating multiple protein conformations to be tested biologically, biochemically, biophysically, and for use in structure-based drug design.

Using genderize.io to infer the gender of first names: how to improve the accuracy of the inference

Objective: We recently showed that genderize.io is not a sufficiently powerful gender detection tool due to a large number of nonclassifications. In the present study, we aimed to assess whether the accuracy of inference by genderize.io can be improved by manipulating the first names in the database.Methods: We used a database containing the first names, surnames, and gender of 6,131 physicians practicing in a multicultural country (Switzerland). We uploaded the original CSV file (file #1), the file obtained after removing all diacritic marks, such as accents and cedilla (file #2), and the file obtained after removing all diacritic marks and retaining only the first term of the compound first names (file #3). For each file, we computed three performance metrics: proportion of misclassifications (errorCodedWithoutNA), proportion of nonclassifications (naCoded), and proportion of misclassifications and nonclassifications (errorCoded).Results: naCoded, which was high for file #1 (16.4%), was reduced after data manipulation (file #2: 11.7%, file #3: 0.4%). As the increase in the number of misclassifications was small, the overall performance of genderize.io (i.e., errorCoded) improved, especially for file #3 (file #1: 17.7%, file #2: 13.0%, and file #3: 2.3%).Conclusions: A relatively simple manipulation of the data improved the accuracy of gender inference by genderize.io. We recommend using genderize.io only with files that were modified in this way.

Fundamental Aspects of Audio and Music Signals

This chapter introduces and explores some basic aspects of audio and music signal processing. It first looks at analogue signals, developing in good detail the concepts of frequency, phase, and amplitude, supported by some mathematics. Simple manipulation of signals is discussed and its effects on sound waveforms are shown. The key concept of discrete signals, and the discretisation process involved in sampling is introduced. The chapter concludes with the definition of digital audio.

Suppression of Circadian Timing and Its Impact on the Hippocampus

In this article, I describe the development of the disruptive phase shift (DPS) protocol and its utility for studying how circadian dysfunction impacts memory processing in the hippocampus. The suprachiasmatic nucleus (SCN) of the Siberian hamster is a labile circadian pacemaker that is easily rendered arrhythmic (ARR) by a simple manipulation of ambient lighting. The DPS protocol uses room lighting to administer a phase-advancing signal followed by a phase-delaying signal within one circadian cycle to suppress clock gene rhythms in the SCN. The main advantage of this model for inducing arrhythmia is that the DPS protocol is non-invasive; circadian rhythms are eliminated while leaving the animals neurologically and genetically intact. In the area of learning and memory, DPS arrhythmia produces much different results than arrhythmia by surgical ablation of the SCN. As I show, SCN ablation has little to no effect on memory. By contrast, DPS hamsters have an intact, but arrhythmic, SCN which produces severe deficits in memory tasks that are accompanied by fragmentation of electroencephalographic theta oscillations, increased synaptic inhibition in hippocampal circuits, and diminished responsiveness to cholinergic signaling in the dentate gyrus of the hippocampus. The studies reviewed here show that DPS hamsters are a promising model for translational studies of adult onset circadian dysfunction in humans.

Evaluation of a Practice System Supporting Distributed Practice for Novice Programming Students

Programming is an important skill in the 21st century, but it is difficult for novices to learn. To help students practice and learn efficiently, the authors developed a mobile platform called Daily Quiz, which incorporated distributed practice theory. To evaluate the impact of distributed practice in programming learning facilitated by Daily Quiz, the authors conducted a between-subject experiment with 200 freshmen divided into two groups. Both groups received the same number of multiple-choice questions via Daily Quiz. However, the control group was encouraged to practice every 7 days, whereas the experimental group was encouraged to practice every 3 days. The results showed that this simple manipulation significantly improved the experimental group’s performance on final exams. Further analysis revealed that the experimental group of students achieved a higher rate of first-check correctness and tended to be more engaged in academic social interaction. Finally, a behavioral sequence analysis was adopted to compare the behavioral patterns of the two groups to investigate how distributed practice helped the students learn more efficiently.

A rearrangement of saccharin-derived cyclic ketimines with 3-chlorooxindoles leading to spiro-1,3-benzothiazine oxindoles

An unusual rearrangement of saccharin-derived cyclic ketimines (SDCIs) and 3-chlorooxindoles has been developed to provide a series of spiro-1,3-benzothiazine oxindoles. The reaction features simple manipulation, short reaction time, mild reaction...

Pd-catalyst Anchored on Schiff Base-modified Chitosan-CNT Nanohybrid for the Suzuki–Miyaura Coupling Reaction

A novel Pd-nanoparticle-catalyst supported on chitosan-pyridine-modified carbon nanotube (CNT) was prepared. The obtained Pd-catalytic platform (Pd@CS-Py@CNT) was fully characterized and employed to the Suzuki–Miyaura coupling reaction as a heterogeneous catalyst, showing an excellent catalytic activity in aqueous media in the absence of phase transfer agents. Moreover, the easy recoverability and reusability of the catalytic system after a simple manipulation is a great benefit.

A Solution for Obtaining an Advanced Lamella Geometry on the Grid with a Single Manipulation Step

A protocol for obtaining an advanced TEM lamella geometry using FIB-SEM is presented. Lamella lift-out procedure might require multiple manipulation steps or even breaking the vacuum in order to reach inverted or plan-view lamella geometries. We have developed a setup which enables lamella transfer from a bulk sample onto a TEM grid within a single, very simple manipulation step, with no need to break the vacuum or unload the sample. Most importantly, this approach does not require any additional devices to be installed.

Pd-catalyst Anchored on Schiff Base-modified Chitosan-CNT Nanohybrid for the Suzuki–Miyaura Coupling Reaction

A novel Pd-nanoparticle-catalyst supported on chitosan-pyridine-modified carbon nanotube (CNT) was prepared. The obtained Pd-catalytic platform (Pd@CS-Py@CNT) was fully characterized and employed to the Suzuki–Miyaura coupling reaction as a heterogeneous catalyst, showing an excellent catalytic activity in aqueous media in the absence of phase transfer agents. Moreover, the easy recoverability and reusability of the catalytic system after a simple manipulation is a great benefit.