Drug and alcohol abuse elicits significant biological changes in the brain that drive compulsive behavior and lead to addiction. A new book from CSHL Press, Addiction, reviews the cell and molecular biology of drug addiction. It was edited by R. Christopher Pierce and Paul J. Kenny.

“Our goal was to highlight a cross-section of innovative contemporary addiction research,” write Pierce and Kenny. Contributors explore the biological basis of addiction to alcohol, nicotine, and other psychoactive drugs. They describe the molecular targets of these drugs, the resulting changes to neural networks, and the various genetic, developmental, and behavioral factors that influence the progression from abuse to addiction.

Addiction will be a useful resource for neuroscientists and all who are interested in reducing the public health burden of substance abuse.  For more details on the book, click here.

Imaging in Neuroscience, the manual from our imaging series that focuses on methods for studying neurons and their circuits, is given a positive review in the current issue of The Quarterly Review of Biology.

 “The most important feature of the manual is the protocol[s] provided,” write Lynne Oland and Patty Jansma. “These are clearly written with the intent of providing the gory detail needed to actually use the protocols successfully, and most chapters include troubleshooting hints, which are most helpful.”

 Oland and Jansma feel that the protocols on glial cells and brain pathology “will make the manual especially useful.” Some of these protocols are available online from Cold Spring Harbor Protocols: For example, check out how to visualize microglia in the mouse cortex, label astrocytes with sulforhodamine 101, and study neural networks in mouse models of Alzheimer’s disease. For more information on the manual, click here.

Protein Synthesis and Translational Control“Situated at the nexus between nucleic acids and proteins, the importance of translational control, now appreciated for its role in establishing the cell’s proteome, is comparable to that of transcriptional control,” write John Hershey, Nahum Sonenberg, and Michael Mathews, editors of our recently released book Protein Synthesis and Translational Control. “It is especially important in defining the proteome, maintaining homeostasis, and controlling cell proliferation, growth, and development.”

The book covers our current understanding of all aspects of protein synthesis and its regulation. Contributors describe the fundamental steps in protein synthesis (initiation, elongation, and termination), the factors involved, and high-resolution structures of the translational machinery where this takes place.  They also review the targets of translational control (e.g., initiation factors and mRNAs) and how signaling pathways modulate this machinery.  The book will be useful to cell and molecular biologists, as well as cancer biologists and others who study human diseases associated with translation dysfunction. For more information, click here.

Basic Stereology for Biologists and NeuroscientistsHow does one determine the size of an organelle? The length of a mass of capillaries? The number of synapses in the brain?

Stereological techniques can be used to estimate the number, length, surface area, and volume of structures in biological cells and tissues. Measurements are made on two-dimensional images or sections of a structure, and then mathematical rules are applied to generate a meaningful description of its three-dimensional geometry. Our newest book, Basic Stereology for Biologists and Neuroscientists, provides a practical guide to designing and critically evaluating stereological studies of the nervous system and other tissues.

“Over the past two decades, a large number of scientific papers have been published that collectively represent a paradigm shift in thinking about how to derive meaningful quantitative data about structural features in biological tissues,” writes the author, Mark West. “These are the design-based, unbiased stereological methods.”

These new stereological methods, the focus of the book, are introduced in “Introduction to Stereology,” a freely accessible article from Cold Spring Harbor Protocols. The book will be essential reading for neurobiologists and cell biologists interested in generating accurate representations of cell and tissue architecture.  For more information, click here.

A newborn’s blood spotted onto a Guthrie card. Photo: The New York State Department of Health Newborn Screening Program.

Over the last 50 years, the spotting of newborn’s blood onto filter paper for disease screening, called Guthrie cards, has become so routine that since 2000, more than 90% of newborns in the United States have had Guthrie cards created.  In a study published online in Genome Research (www.genome.org), researchers have shown that epigenetic information stored on archived Guthrie cards provides a retrospective view of the epigenome at birth, a powerful new application for the card that could help understand disease and predict future health.

DNA methylation, an epigenetic chemical modification of DNA, is known to affect gene activity and play a role in normal development, aging, and also in diseases such as heart disease, diabetes, and cancer.  “But are these epigenetic marks involved in causing the disease, or a result of the disease itself?” asked Dr. Vardhman Rakyan of Queen Mary, University of London and co-senior author of the study.  Rakyan explained that this is impossible to know when samples are obtained after onset of the disease.  Guthrie cards, commonly used to collect blood spots from the pricked heel of newborns to screen for diseases such as phenylketonuria, cystic fibrosis, and sickle cells disorders, might offer a snapshot of the epigenome before disease develops.  Many Guthrie cards are stored indefinitely by health authorities around the world, posing a potential wealth of information about the epigenome at birth.

Rakyan and an international group of colleagues purified genomic DNA and analyzed DNA methylomes from Guthrie cards and verified that this archived DNA yields high-quality methylation data when compared to fresh samples.  The researchers then compared the DNA methylation profiles of newborns to the same healthy individuals at the age of three, looking for epigenetic variations detected in the Guthrie card sample that are stable into the early years of life.

“We found similar epigenetic differences between different people both at birth and when they were three years old,” said Rakyan, who added that these differences, already present at birth, are unlikely due solely to inherent genetic differences between the individuals, but also due to environment or random events in utero.  Furthermore, Guthrie card samples could be analyzed for both genetic and epigenetic differences together to view a more complete picture of the genome at birth.

Guthrie card methylomics is a potentially powerful new application for archived blood spots, which could provide a wealth of information about epigenetics and disease, and could give clues about health later in life.  Dr. David Leslie, co-senior author of the study, added that because national health authorities routinely make Guthrie cards available, and with the proper consent obtained from parents and children, “we are talking about an invaluable, and non-renewable, resource for millions of individuals.”

“The shaking palsy,” as it was first described by James Parkinson in 1817, is a disabling neurodegenerative disorder common among the elderly. Parkinson’s Disease, a new book edited by Serge Przedborski, provides a current review of the disease, from its neuropathological and clinical bases to diagnostic challenges and therapeutic interventions.

The book is “designed specifically to bridge the clinical and basic science aspects of Parkinson’s disease under one cover,” writes Przedborski. It will be useful for neurobiologists, cell biologists, and pathologists pursuing the biological basis of Parkinson’s disease, as well as scientists and clinicians interested in its diagnosis and treatment.

Contributors discuss the mutations in genes encoding proteins such as α-synuclein, parkin, and LRRK2 that cause Parkinson’s disease; the roles of mitochondria, autophagy, protein quality control, and programmed cell death in disease progression; and the chemistry and anatomy of the basal ganglia that are affected. The use of functional neuroimaging and experimental models to probe the neurobiology of Parkinson’s disease are also described. For more information, click here.

From exercise to aging, metabolism plays a central role in normal physiology. Metabolic imbalances contribute to major diseases such as obesity, cancer, and diabetes. Our new volume Metabolism and Disease combines some of the most stimulating work on metabolism and its dysregulation.

The book’s 44 chapters are based on presentations by researchers at last year’s Cold Spring Harbor Symposium on Quantitative Biology. Contributors review the latest advances in our molecular understanding of energy consumption, storage, and homeostasis.  Topics include cell signaling and gene regulation in metabolic control; fat metabolism and its regulation; circadian clocks and aging; apoptosis and autophagy; and cancer.

Articles are also available online at http://symposium.cshlp.org/. For more information, click here.