Similar Fates Research Articles

Bypassing Big Pharma

There have been many resounding victories in the war against coronary artery disease. Among those are antiarrhythmic drugs, pacemakers, coronary bypass surgery, coronary angioplasty, reperfusion therapy, and statins. But the one goal that has continuously eluded us has been the clinical availability of an effective cardioprotective agent. Although reperfusion therapy has partially achieved the goal of limiting infarct size in the setting of acute myocardial infarction, the logistics usually prevent restoration of perfusion until after a significant amount of myocardium has been lost to infarction. In 1974, when Braunwald1 proposed that priority should be given to the identification of interventions that would make the myocardium resistant to infarction, nobody knew what an arduous task that would be. In the beginning, “big pharma” was a strong partner in this quest, and many drugs were evaluated. The first wave of drugs like β-blockers and calcium antagonists were examined because it was believed that they would reduce oxygen consumption and that an improvement in the supply-demand relationship in the heart would suppress infarction. Unfortunately, the determinants of oxygen consumption in the ischemic heart are very different from those in the well-perfused heart, and not surprisingly, these drugs were ineffective. Then, the focus shifted to antioxidants and antiinflammatory agents. Their preclinical performance was inconsistent, and the clinical trials that they spawned were all decidedly negative. Most recently, a great deal of money was spent on the development of the sodium–hydrogen exchange blocker cariporide, which again failed in clinical trials. Adenosine and insulin suffered similar fates. With each negative trial, the industry has become increasingly leery of cardioprotective interventions, and most companies are now very reluctant to include primary cardioprotectants in their development pipelines. Nobody knows …

Family effects on early survival and variance in long‐term reproductive success of female cheetahs

1. While it is generally accepted that the survival of offspring within families may be correlated, the extent of correlation has been largely untested. Furthermore, the impact of such correlation on the estimated variance in females' reproductive success has rarely been quantified. 2. Here we use an exceptional data set from a long-term study of individually recognized cheetahs from the Serengeti National Park in Tanzania to formally quantify family effects in carnivores. 3. We show (i) that cubs from the same litter exhibit more similar fates than unrelated cubs when it comes to first-year survival; and (ii) that the observed variance of the long-term reproductive success of females is twice the variance expected under the assumption of complete independence of fates between cubs. 4. We suggest that family effects are likely to be widespread in vertebrates with average litter sizes > 1, and could have important consequences for population dynamics and population viability analyses.

Endangered Scholars Worldwide: Introduction

Endangered Scholars Worldwide: Introduction IN TH IS ISSUE OF SOCIAL R ESEA R CH WE ARE INTRODUCING A N E W FEATURE that we hope will appear regularly in our pages. We resolve to dedicate a section ofeachfuture issue to a listing ofendangered and imprisoned scholars worldwide. We will publish the names ofthese scholars and provide sources of further details, along with as much information as we can about what actions we are being asked to take on their behalf. We recognize that there are many organizations both in the United States and elsewhere already doing this work, but we think adding our voice to those already speaking up can only help put pressure on the people and states responsiblefor these injustices. Our hope is that world opinion will help persuade them to free the individuals they unjustly imprison and persecute. We see this new effort as completely consistent not only with our own history as a journal but with the intensifying need to call attention to the increasing, often brutal, attempts to silence our colleagues around the world. Those of our readers who are familiar with the history of Social Research may know that it was launched in 1934 by the small group ofEuropean schol­ ars whom AlvinJohnson, the New School’sfirstpresident, rescuedfrom Hitler’s Germany and the spread offascism throughout Europe. The New School for Social Research (formerly known as the Graduate Faculty) began with this group ofexiles, who constituted what was originally known as the “University in Exile.” Social Research: An International Q uarterly of the Political and Social Sciences was established as the voice of these rescued and exiled scholars and intellectuals. Now, almost 75 years later, we once again wish to provide a voice for endangered and imprisoned scholars everywhere, and we think ourfounders would enthusiastically endorse this effort. Endangered Scholars W orldw ide v A word about why now: We have been motivated to launch this effort in response to the illegal arrest of two people who in the recent past were members of the New Schoolfamily. One of those arrested, Dr. Kian Tajbakhsh, is a friend, a Social Research author, and was a colleague at the New School from 1994 until 2001, teaching urban policy and politics. The other is Dr. Berhanu Nega, who received his Ph.D. in Economics from the New Schoolfor Social Research in 1991. We are initiating this special feature by singling out Kian Tajbakhsh and Berhanu Nega from the many other scholars and intellectuals suffering similar fates— such as Haleh Esfandiari, who also was arrested by Iranian authorities on May 8, 2007 and is also being held in Evin Prison in Tehran, or Professor Mesfin Woldemariam, who, like Dr. Nega, was arrested in Ethiopia in 2005 and remains in prison— because Doctors Tajbakhsh and Nega are part of our immediate family. In subsequent issues we will spread our atten­ tion globally, wherever it is needed, and provide information about scholars everywhere who are endangered sometimes for simply doing their scholarly work and sometimes for speaking out against the injustices around them. —Arien Mack, Editor “ Endangered Scholars Worldwide," the title of the new section that debuts this month in Social Research, succinctly sums up an urgent and ongoing matter ofgrave concern. It is onlyfitting that The New School, originallyfounded to provide a safe havenfor intellectuals at risk, joins the community ofthose dedi­ cated to calling attention to and taking action on behalfofthosefacing danger. I wholeheartedly applaud this inspired effort to champion the cause ofmembers of our “ family,”as well as other imperiled scholars across the globe. —Bob Kerrey, President, The New School vi social research ...

Notch It Up: Nudging Stem Cells toward a Neural Fate

From the black widow spider to the six-toed sloth, every multicellular organism starts life as a single cell. This cell and the embryonic stem cells it spawns will live or die, grow, proliferate, migrate, and differentiate at the direction of a tightly controlled genetic program. Embryonic stem cells can self-renew to produce populations of identical cells that retain the ability to turn into any cell type of the body, a feature called pluripotency. Identifying the molecular signals that govern the maintenance and release of the pluripotent state would help scientists refine their ability to use embryonic stem cells as models of disease, as test beds for drug screening, and as a source for cell-based therapies. Researchers are particularly interested in uncovering the early signals that commit a cell to a particular fate, such as a skin, gut, or nerve cell. Cell fate is determined in a wide variety of vertebrates and invertebrates by proteins called Notch receptors, which straddle the membrane of cells and transmit signals through local cell interactions. Depending on the context, Notch signaling can inhibit the spread of differentiation among adjacent cells or prompt them to adopt similar fates. In a new study, Sally Lowell, Austin Smith, and their colleagues discovered that Notch signaling also induces embryonic stem cells to make the initial commitment to a nervous system fate. Working with undifferentiated mouse embryonic stem cells, Lowell et al. first confirmed that the cells express both the Notch receptor and its activators, or ligands. When the Notch pathway is activated, the receptor's intracellular domain (NotchIC) detaches and enters the nucleus. Once inside the nucleus, NotchIC binds to and activates the RBPJκ transcription factor, which in turn activates target genes. To boost Notch signaling without having to depend on complex ligands, the researchers engineered a transgene to allow ongoing, moderate expression of active NotchIC. Cells that showed this constitutive NotchIC expression, termed R26NotchIC cells, served as the experimental model. These cells come from an embryonic stem cell line (called 46C) that has green fluorescent protein linked to a neural specification marker gene (Sox1), making it easy to identify cells that choose a neural fate. With a suitable experimental system in hand, Lowell et al. released R26NotchIC cells and a control cell line from the influence of self-renewal factors in order to allow differentiation. By the second day, they saw a roughly 3-fold increase in glowing Sox1-expressing cells compared with the control line. The researchers also observed reduced levels of a key marker of pluripotency (Oct4) and sharp increases of a protein associated with the initial stages of differentiation (FGF5). These findings, along with the observation that R26NotchIC cells give rise to a coherent mass of glowing Sox1 cells, indicate that NotchIC accelerates the onset of neural differentiation. The researchers go on to show that Notch not only guides cells into a neural fate—amplifying and coordinating induction within a cell population—but also restricts them from choosing other fates. To investigate whether NotchIC is necessary for neural induction, the researchers interfered with Notch activity. When 46C cells were treated with an agent that blocks Notch activation by preventing cleavage of its intracellular domain, the number of cells that activated the Sox1 neural marker was reduced to only 10% of normal, and most retained expression of the Oct4 pluripotency marker. Eventually, the cells differentiated, but not into neural cells. When this inhibitor was used to treat R26NotchIC cells, which have the already-cleaved receptor, Sox1 expressed was unaffected; thus, the anti-neural effects come specifically from blocking Notch signaling. Using embryonic stem cell lines without functional RBPJκ genes (needed to activate Notch's target genes) produced similar results: the cells yielded far fewer Sox1 cells and either retained Oct4 or differentiated into a non-neural cell type. Finally, Lowell et al. tested Notch's effects in human embryonic stem cells and show that it works much like it does in mouse stem cells, guiding them toward a neural fate. By revealing an unexpected role for Notch in directing early differentiation, the researchers have identified a key molecular determinant of stem cell regulation. As scientists identify more and more of these critical molecular cues, the closer they will come to harnessing the power and promise of these much-embattled, protean cells.

Keeping Afloat: A Strategy for Small Island Nations

Looking for some adventure? Then how about a trip to Fiji, the Caribbean, or the Seychelles? With their palm trees, lazy beaches, and clear turquoise waters, few places have more appeal than the world’s island nations. Roughly 40 such countries, some sovereign and others not, lie scattered across the planet, ranging in size from Papua New Guinea, with a land area of 452,860 square kilometers and more than 5 million citizens, to Tokelau, a tiny, self-administering territory of New Zealand with a land mass measuring just 10 square kilometers and a population of 1,400. Perhaps surprisingly, there is no clear official definition for what constitutes an island nation. The Alliance of Small Island States (AOSIS), an ad hoc lobbying and negotiation organization that coordinates the most prominent grouping, refers to its 45 members as “small island developing states,” or SIDS. The criteria that define SIDS are somewhat ambiguous, however. AOSIS members include Belize, Guinea-Bissau, Guyana, and Suriname, which are all coastal—although not technically island—nations. The upper population limit for SIDS, which is 10 million, also appears flexible: AOSIS counts Cuba as a member, despite the country’s population of 11.3 million. AOSIS has even received an application from Madagascar, despite that country’s population of 18 million. Island nations may be beautiful, but their isolation makes them vulnerable to outside forces that increasingly threaten their survival. Rising sea levels linked to global warming could submerge some altogether. Tuvalu, a West Pacific nation whose peak height rises just 5 meters over sea level, could be uninhabitable within 50 years, some experts say. A similar fate could also doom the Maldives, the Marshall Islands, Kiribati, and Tokelau. Meanwhile, for reasons not entirely understood, hurricane activity in the tropics appears to be increasing. Hurricane Ivan—the sixth most intense Atlantic hurricane on record—blasted the Caribbean with 160-mile-per-hour winds in 2004, devastating most of Grenada’s housing and virtually destroying its economy within just a few hours. The 2005 Caribbean hurricane season made headlines early on with Dennis in July. This earliest powerful hurricane ever recorded in the region caused an estimated US$5–9 billion in damage. Most island nations struggle daily with depleted fish stocks, inadequate waste management, ship pollution, degraded reefs, dwindling freshwater supplies, and poverty. In general, the farther an island nation is from global markets, the poorer it is. Distance makes everything more expensive; oil prices in particular tend to be extremely high owing to transportation costs. The more remote islands also tend to lack communications infrastructure, access to information technology, and adequate numbers of trained professionals, including engineers, doctors, and teachers. These technical limitations slow economic development and exacerbate environmental problems caused by poor management of island resources. Island nations are also uniquely threatened by price shocks from economic globalization. Most island nations depend heavily on tourism, foreign aid, and a limited range of exports like sugar and bananas. Declines in any of these sectors can decimate revenue streams, exacerbating the poverty that already plagues these countries. In St. Lucia, export revenue from bananas plunged from US$46 million in 1996 to US$22 million in 2002, largely because cheaper bananas from Central America flooded world markets during that same period. According to Kishan Kumarsingh, technical coordinator at the Environmental Management Authority in Trinidad and Tobago, climate change can also alter growing conditions, affecting agricultural productivity. Price shocks emanate in part from the World Trade Organization’s (WTO) trade liberalization policies, which are dismantling arrangements that traditionally have guaranteed markets for island exports. A preferential trade link between the European Union and African, Caribbean, and Pacific Island exporters known as the EU–ACP Agreement is being phased out by the WTO after 30 years in existence as part of a deliberate effort coordinated by the organization to reduce protectionism and open economies to more globalized trade. Its elimination already hurts Caribbean banana exports, as indicated by St. Lucia’s experience. Sugar exports from Pacific countries could suffer similar fates, says Francois Coutu, a spokesperson in the United Nations (UN) Department of Public Information. With environmental and economic problems mounting, island nations are turning increasingly to donor countries for aid. But these sources, too, are dwindling: donor nations’ development aid to island nations decreased from a high of US$2.3 billion in 1995 to US$1.7 billion in 2005, according to the UN Small Island Development Unit.

HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cells

Genetic manipulation of hematopoietic stem and progenitor cells is an important tool for experimental and clinical applied hematology. However, techniques that allow for gene targeting, subsequent in vitro selection, and expansion of genetically defined clones are available only for ES cells. Such molecularly defined and, hence, "safe" clones would be highly desirable for somatic gene therapy. Here, we demonstrate that in vitro differentiated ES cells completely recapitulate the growth and differentiation properties of adult bone marrow cells, in vitro and in vivo, when ectopically expressing HOXB4. Myeloid development was enforced and (T) lymphoid development suppressed over a wide range of expression levels, whereas only high expression levels of the transcription factor were detrimental for erythroid development. This indicates a close association between the amounts of ectopic HOXB4 present within a progenitor cell and and the decision to self renew or differentiate. Because HOXB4 mediates similar fates of ES-derived and bone marrow hematopoietic stem cells, the primitive embryonic cells can be considered a promising alternative for investigating hematopoietic reconstitution, in vivo, based on well defined clones. Provided that HOXB4 levels are kept within a certain therapeutic window, ES cells also carry the potential of efficient and safe somatic gene therapy.

Block Grant Head Start? Devolution's Potential Negative Impact on Children and Families

The “new federalism” paradigm offers an explanation why the federal government has devolved much of its administration of the Temporary Assistance for Needy Families (TANF, formerly AFDC) and Medicaid (through managed care) programs. A review of child and family outcomes data resulting from these devolutionary changes in TANF and Medicaid indicates that these devolutionary changes generally appear to have decreased access to medical coverage, decreased well-being outcomes, decreased cognitive development, increased behavioral and emotional difficulties, and increased the incidence of poor health for children and families. If the “new federalism” paradigm is extended to the Head Start program by block granting it to the states, children and their families served by Head Start are in potential jeopardy of suffering similar fates. This strong possibility should make policy makers very cautious about devolving or block granting the Head Start program to the states.

Patriotism, Pledging Allegiance, and Public Schools: Lessons from Washington County in the 1940s

THE PLEDGE OF ALLEGIANCE, first composed in nineteenth century, has once again become a topic of considerable editorial comment and political posturing in twenty-first century, as seventeen states have enacted new pledge laws or amended existing statutes.1 Nonetheless, there is little evidence that many citizens or elected officials are aware of history and consequences of attempts by patriotic organizations, local school districts, and state governments to define and require expressions of appropriate sentiments about nation's flag. This essay examines incidents at two schools in Washington County, Arkansas, during early 1940s, when public school children refused to pledge allegiance to because of their religious beliefs and suffered consequences. While these were certainly not only instances of controversy over salute in Arkansas schools in that period, Washington County episodes serve as an effective case study. They suggest something of motives, actions, and experiences of those involved in similar incidents across Arkansas and nation. The school movement began in 1888, when James Upham, head of premium department of Youth s Companion magazine, launched a four-year campaign to encourage display of United States flags in school classrooms, in order both to sell flags and to promote patriotism. The following year, Col. George Thatcher Balch introduced an American salute in his New York City kindergarten class, requiring students to stretch their right arm forward while pledging, We give our heads and our hearts to God and our country; one country, one language, one Flag. Balch spread his ideas for inculcating by publishing a book, Methods of Teaching Patriotism in Public Schools, in 1890. Youth's Companion had already sold over 25,000 flags to public schools when it first published Pledge of Allegiance in its issue of September 8, 1892. It wished to promote nationalism in schools during celebration of that October's 400th anniversary of Columbus's arrival in Americas. Written by Francis Bellamy, a thirty-year-old assistant to editor of magazine, Pledge originally read, I pledge allegiance to Flag and to Republic for which it stands: one Nation indivisible, with Liberty and Justice for all. Leaflets containing Pledge were distributed to public schools, and an estimated twelve million students recited Pledge on Columbus Day, 1892.3 The drums of war, as always, found public officials and professional patriots ready to seek national unity through force of law. In 1898, as United States went to war with Spain, New York legislature passed first statute mandating that each public school day open with a salute to and other patriotic exercises. What had begun as a youth magazine's publicity campaign to promote patriotism and sell flags had become a ritual required by law. During World War I, children of Mennonites were expelled from schools for refusing on religious grounds to recite Pledge of Allegiance, and, during 1920s, public school students of various religious backgrounds suffered similar fates from Delaware to Denver.4 During Red Scare following World War I, American Legion, Daughters of American Revolution, and other patriotic organizations urged public schools to stress 100 percent Americanism in curriculum. Arkansas was among states that acted. In 1923, General Assembly adopted laws requiring display of American at all educational institutions in state and mandating teaching of patriotism, both of which remain on statute books today.5 That summer, American Legion led call for first National Flag Conference to meet in Washington, D.C., and changed wording of Pledge of Allegiance, replacing my flag with the of United States, so that immigrants and their children could not covertly pledge allegiance to flags of their countries of origin. …

Science and celebrity

Science and celebrity

A CIITA-independent pathway that promotes expression of endogenous rather than exogenous peptides in immune-privileged sites.

A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class II in response to IFN-gamma alone, these cells readily expressed MHC class II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-gamma and TNF-alpha. CIITA-independent expression of MHCclass II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T cells. To determine whether CIITA-independent expression of MHC class II is relevant in vivo, minor H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class II KO mice or wild-type donors were placed in eyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class II-deficient corneas were rejected. In addition, MHC class II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens.

EDL/MAE regulates EGF-mediated induction by antagonizing Ets transcription factor Pointed.

Inductive patterning mechanisms often use negative regulators to coordinate the effects and efficiency of induction. During Spitz EGF-mediated neuronal induction in the Drosophila compound eye and chordotonal organs, Spitz causes activation of Ras signaling in the induced cells, resulting in the activation of Ets transcription factor Pointed P2. We describe developmental roles of a novel negative regulator of Ras signaling, EDL/MAE, a protein with an Ets-specific Pointed domain but not an ETS DNA-binding domain. The loss of EDL/MAE function results in reduced number of photoreceptor neurons and chordotonal organs, suggesting a positive role in the induction by Spitz EGF. However, EDL/MAE functions as an antagonist of Pointed P2, by binding to its Pointed domain and abolishing its transcriptional activation function. Furthermore, edl/mae appears to be specifically expressed in cells with inducing ability. This suggests that inducing cells, which can respond to Spitz they themselves produce, must somehow prevent activation of Pointed P2. Indeed hyperactivation of Pointed P2 in inducing cells interferes with their inducing ability, resulting in the reduction in inducing ability. We propose that EDL/MAE blocks autocrine activation of Pointed P2 so that inducing cells remain induction-competent. Inhibition of inducing ability by Pointed probably represents a novel negative feedback system that can prevent uncontrolled spread of induction of similar cell fates.

Infectious disease in Haiti. HIV/AIDS, tuberculosis and social inequalities.

More than 50 years after the introduction of chemotherapy for the treatment of tuberculosis (TB), the disease is far from being under control. Among curable infectious diseases, TB remains the number‐one killer—each year, 2 million people still die of the disease and 8.4 million more fall ill (World Health Organization (WHO), 2002a). And future projections are grim. Fewer than half of all TB cases are diagnosed, and of those that are, fewer than 30% have access to the care recommended by the WHO (WHO, 2002a). The increase in TB worldwide is due, in part, to the expansion of the HIV/AIDS pandemic (WHO, 2001): at least one‐third of people with HIV die of TB (WHO, 2002a). HIV/AIDS now causes more than 3 million deaths per year (UNAIDS, 2002). More than 90% of HIV/AIDS deaths and new infections occur in poor countries where less than 5% of those who need antiretroviral treatment have access to these therapies (WHO, 2002b). If we consider that, on average, 10% of people with HIV need antiretroviral treatment, the 5% figure comes down to less than 1% in sub‐Saharan Africa, the region most affected by the pandemic. > The social contexts in which our patients became infected are an integral part of their stories Large‐scale social forces, such as racism, sexism, political violence, poverty and other social inequalities, are rooted in historical and economic processes and sculpt the distribution and outcome of HIV/AIDS and TB. We refer to these social forces as ‘structural violence’ (Castro & Farmer, 2002, 2003a,b; Farmer, 2003), which predisposes the human body to pathogenic vulnerability by shaping the risk of infection and subsequent disease reactivation. After infection, structural violence also determines who has access to diagnostics and effective therapy. Drugs that could stop or slow down these epidemics, such as …

Living Fast, Dying When? The Link between Aging and Energetics

The idea that aging should be linked to energy expenditure has a long history that can be traced to the late 1800s and the industrial revolution. Machines that are run fast wear out more quickly, so the notion was born that humans and animals might experience similar fates: the faster they live (expressed as greater energy expenditure), the sooner they die. Evidence supporting the "rate-of-living" theory was gleaned from the scaling of resting metabolism and life span as functions of body mass. The product of these factors yields a mass-invariant term, equivalent to the "amount of living." There are at least four problems with this evidence, which are summarized and reviewed in this communication: 1) life span is a poor measure of aging, 2) resting metabolism is a poor measure of energy expenditure, 3) the effects are confounded by body mass and 4) the comparisons made are not phylogenetically independent. We demonstrate that there is a poor association between resting metabolic rate (RMR) and daily energy expenditure (DEE) measured using the doubly labeled water (DLW) method at the level of species. Nevertheless, the scaling relation between DEE and body mass still has the same scaling exponent as the RMR and body mass relationship. Thus, if we use DEE rather than RMR in the analysis, the rate-of-living ideas are still supported. Data for 13 species of small mammal were obtained, where energy demands by DLW and longevity were reliably known. In these species, there was a strong negative relationship between residual longevity and residual DEE, both with the effects of body mass removed (r(2) = 0.763, F = 32.1, P < 0.001). Hence, the association of energy demands and life span is not attributed to the confounding effects of body size. We subjected these latter data to an analysis that extracts phylogenetically independent contrasts, and the relationship remained significant (r(2) = 0.815, F = 39.74, P < 0.001). Small mammals that live fast really do die young. However, there are very large differences between species in the amounts of living that each enjoy and these disparities are even greater when other taxa are included in the comparisons. Such differences are incompatible with the "rate-of-living" theory. However, the link between energetics and aging across species is reconcilable within the framework of the "free-radical damage hypothesis" and the "disposable soma hypothesis." Within species one might anticipate the rate-of-living model would be more appropriate. We reviewed data generated from three different sources to evaluate whether this were so, studies in which metabolic rate is experimentally increased and impacts on life span followed, studies of caloric restriction and studies where links between natural variation in metabolism and life span are sought. This review reveals that there might be contrasting effects of resting and nonresting energy expenditure on aging, with increases in the former being protective and increases in the latter being harmful.

Alfred Hauptmann - the fate of a german neurologist of jewish origin

The pathway through life of the German psychiatrist and neurologist Alfred Hauptmann (1881 - 1948) and his work is described. It is exemplary for so many of his contemporaries of Jewish origin, who were forced to emigrate under the National Socialist dictatorship. Hauptmann's career was most of all marked by the short, but to him formative time with Max Nonne. Throughout his life his research focused on neurological topics. In 1926, Hauptmann got the chair of psychiatry at Halle University in order to continue the important neurological tradition of Eduard Hitzig, Carl Wernicke and Gabriel Anton. Until 1935, he worked as the director of the psychiatric clinic in Halle, but in the course of the Reichsbürgergesetz he had to give up his chair and his work as a doctor. The way into emigration, which was accelerated by the temporary imprisonment in the concentration camp Dachau, is described considering personal documents. After his emigration into the United States, Hauptmann was not too successful in starting new as a scientist. His most important contribution is still the article on the efficacy of Phenobarbital as an antiepileptic, which had been written already in 1912. For this reason, the Alfred-Hauptmann-Award for epilepsy research is awarded. In 1941 - after his emigration - he and Siegfried Joseph Thannhauser described the autosomal dominantly transmitted myopathy for the first time, which is today described as Hauptmann-Thannhauser myodystrophy. The name of Alfred Hauptmann should be unforgettable not only because of the entrance into medical nomenclature, but it should also remind of the man Alfred Hauptmann, standing for all those whose similar fates are still unknown until now.

Rudabánya: A late miocene subtropical swamp deposit with evidence of the origin of the African apes and humans

AbstractRudabánya, a rich late Miocene fossil site in northern central Hungary, has yielded an abundant record of fossil primates, including the primitive catarrhine Anapithecus and the early great ape Dryopithecus. While the affinities of Anapithecus are not clear, Dryopithecus is clearly a great ape sharing numerous characteristics of its dental, cranial and postcranial anatomy with living great apes. Like all Miocene hominids (great apes and humans), Dryopithecus is more primitive in a number of ways than any living hominid, which is probably related to the passage of time since the divergence of the various lineages of living hominids, allowing for similar refinements in morphology and adaptation to take place independently. On the other hand, Dryopithecus (and Ouranopithecus) share derived characters with hominines (African apes and humans), and Sivapithecus (and Ankarapithecus) share derived characters with orangutans, thus dating the split between pongines and hominines to a time before the evolution of these fossil great apes. Pongines and hominines follow similar fates in the late Miocene, the pongines moving south into Southeast Asia from southern or eastern Asia and the hominines moving south into East Africa from the Mediterranean region, between 6 to 9 Ma.

Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome.

Following transcription and splicing, each mRNA of a mammalian cell passes into the cytoplasm where its fate is in the hands of a complex network of ribonucleoproteins (mRNPs). The success or failure of a gene to be expressed depends on the performance of this mRNP infrastructure. The entry, gating, processing, and transit of each mRNA through an mRNP network helps determine the composition of a cell's proteome. The machinery that regulates storage, turnover, and translational activation of mRNAs is not well understood, in part, because of the heterogeneous nature of mRNPs. Recently, subsets of cellular mRNAs clustered as members of mRNP complexes have been identified by using antibodies reactive with RNA-binding proteins, including ELAV/Hu, eIF-4E, and poly(A)-binding proteins. Cytoplasmic ELAV/Hu proteins are involved in the stability and translation of early response gene (ERG) transcripts and are expressed predominately in neurons. mRNAs recovered from ELAV/Hu mRNP complexes were found to have similar sequence elements, suggesting a common structural linkage among them. This approach opens the possibility of identifying transcripts physically clustered in vivo that may have similar fates or functions. Moreover, the proteins encoded by physically organized mRNAs may participate in the same biological process or structural outcome, not unlike operons and their polycistronic mRNAs do in prokaryotic organisms. Our goal is to understand the organization and flow of genetic information on an integrative systems level by analyzing the collective properties of proteins and mRNAs associated with mRNPs in vivo.

Selenium Modifies the Metabolism and Toxicity of Arsenic in Primary Rat Hepatocytes

Arsenic and selenium are metalloids with similar chemical properties and metabolic fates. Inorganic arsenic (iAs) has been shown to modify metabolism and toxicity of inorganic and organic selenium compounds. However, little is known about effects of selenium on metabolism and toxicity of iAs. The present work examines the effects of selenite (SeIV) on the cellular retention, methylation, and cytotoxicity of trivalent iAs, arsenite (iAsIII), in primary cultures of rat hepatocytes. The concurrent exposure to SeIV (0.1 to 6 μM) inhibited methylation and/or significantly increased cellular retention of iAsIII in cultured cells. The ratio of the methylated metabolites produced from iAsIII, dimethylarsenic (DMAs) to methylarsenic (MAs), decreased considerably in cells treated with SeIV, suggesting that synthesis of DMAs from MAs may be more susceptible to inhibition by SeIV than is the production of MAs from iAsIII. The 24-h preexposure to 2 μM SeIV had a similar but less pronounced inhibitory effect on the methylation of iAsIII in cultured cells. The exposure to 2 μM SeIV alone for up to 24 h had no effect on the viability of cultured hepatocytes. However, concurrent exposure to 2 μM SeIV increased the cytotoxicity of iAsIII and its mono- and dimethylated metabolites that contain trivalent arsenic, MAsIII and DMAsIII. These data suggest that pre- or coexposure to inorganic selenium may enhance the toxic effects of iAs, increasing its retention in tissues and suppressing its methylation, which may be a pathway for detoxification of iAs.

An apology for orthologs - or brave new memes.

An apology for orthologs - or brave new memes.

Contact with Isolated Sclerotome Cells Steers Sensory Growth Cones by Altering Distinct Elements of Extension

During pathfinding, growth cones respond to guidance cues by altering their motility. This study shows that motile responses can be highly specific: filopodial contact with two different, physiologically relevant cells differentially alters discrete elements of motility. With each cell type, the responses to contact are invariant. Each cell induces a distinct response in sensory growth cones with every filopodial contact. Contact with an inhibitory cell, posterior sclerotome, alters a discrete motile characteristic; contact locally inhibits the ability of veils to extend down contacting filopodia. The inhibition is precise. Contact fails to alter other individual veil characteristics such as initiation frequency or extension rate. Moreover, despite local veil inhibition, the general level of extension across the growth cone is retained, as though protrusive activity is regulated to some set point. Contact with a stimulatory cell, anterior sclerotome, elicits a biphasic response. First, contact stimulates extension generally, altering the set point of protrusion. Contact increases veils and filopodia throughout the growth cone persistently. Then contacting processes consolidate, forming neurite. Filopodia contacting either cell type have similar lifetimes but different fates. Filopodia contacting posterior cells show morphological indications of structural instability, likely related to their inability to support veil extension. Filopodia contacting anterior cells branch, become morphologically complex, and ultimately consolidate into neurite. The invariance and precision of these responses suggests they are the steering components elicited by contact. These steering components, when integrated with other motile events, modulate growth cone trajectory. The discreteness of these responses suggests that guidance cues affect equally discrete elements in signaling cascades.

An Isotope Dilution Model for Partitioning Leucine Uptake by the Liver of the Lactating Dairy Cow

An isotope dilution model for partitioning leucine uptake by the liver of the lactating dairy cow is constructed and solved in the steady state. If assumptions ae made, model solution permits calculation of the rate of leucine uptake from portal and hepatic arterial blood supply, leucine export into the hepatic vein, leucine oxidation and transamination, and synthesis and degradation of hepatic constitutive and export proteins. The model requires the measurement of plasma flow rate through the liver in combination with leucine concentrations and plateau isotopic enrichments in arterial, portal and hepatic plasma during a constant infusion of [1-13C]leucine tracer. The model can be applied to other amino acids with similar metabolic fates and will provide a means for assessing the impact of hepatic metabolism on amino acid availability to peripheral tissues. This is of particular importance when considering the dairy cow and the requirements of the mammary gland for milk protein synthesis.