The cartwheel is a striking structure critical for building the centriole, a microtubule-based organelle fundamental for organizing centrosomes, cilia, and flagella. Over the last 50 years, the cartwheel has been described in many systems using electron microscopy, but the molecular nature of its constituent building blocks and their assembly mechanisms have long remained mysterious. Here, we review discoveries that led to the current understanding of cartwheel structure, assembly, and function. We focus on the key role of SAS-6 (...) protein self-organization, both for building the signature ring-like structure with hub and spokes, as well as for their vertical stacking. The resemblance of assembly intermediates in vitro and in vivo leads us to propose a novel registration step in cartwheel biogenesis, whereby stacked SAS-6-containing rings are put in register through interactions with peripheral elements anchored to microtubules. We conclude by evoking some avenues for further uncovering cartwheel and centriole assembly mechanisms. The cartwheel is crucial for centriole assembly. Despite this fundamental role, cartwheel structure and assembly mechanisms remain unclear for a long time. Here we review five decades of research that led to our current understanding of these questions, highlighting the central role of the SAS-6 protein family. (shrink)

The centriole is a widely conserved organelle required for the assembly of centrosomes, cilia, and flagella. Its striking feature – the nine‐fold symmetrical structure, was discovered over 70 years ago by transmission electron microscopy, and since elaborated mostly by cryo‐electron microscopy and super‐resolution microscopy. Here, we review the discoveries that led to the current understanding of how the nine‐fold symmetrical structure is built. We focus on the recent findings of the centriole structure in high resolution, its assembly pathways, and its (...) nine‐fold distributed components. We propose a model that the assembly of the nine‐fold symmetrical centriole depends on the concerted efforts of its core proteins. Also see the video abstract here:https://youtu.be/m4h_3II_WJo. (shrink)

This paper offers a critique of Martha Nussbaum’s description of the capability approach, and offers an alternative. I will argue that Nussbaum’s characterization of the capability approach is flawed, in two ways. First, she unduly limits the capability to two strands of work, thereby ignoring important other capabilitarian scholarship. Second, she argues that there are five essential elements that all capability theories meet; yet upon closer analysis three of them are not really essential to the capability approach. I also offer (...) an alternative description of the capability approach, which is called the cartwheel view of the capability approach. This view is at the same time radically multidisciplinary yet also contains a foundationally robust core among its various usages, and is therefore much better able to make the case that the capability approach can be developed in a very wide range of more specific normative theories. Finally, the cartwheel view is used to argue against Nussbaum's claim that all capabilitarian political theory needs to be politically liberal. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 10.1 (2003) 57-62 [Access article in PDF] Listening to People Or Listening to Prozac?Another Consideration of Causal Classifications Jennifer Hansen Keywords causal classification, descriptivism, melancholia, neurasthenia, depression, cultural relativism. The shape and detail of depression have gone through a thousand cartwheels, and the treatment of depression has alternated between the ridiculous and the sublime, but the excessive sleeping, inadequate eating, suicidiality, withdrawal from social interaction, (...) and relentless despair are all as old as the hill tribes, if not as old as the hills. In the years since man achieved the capacity for self-reference, shame has come and gone; treatments for bodily complaints have alternated and crossed with treatments for spiritual ones; pleas to external gods have echoed pleas to internal demons. To understand the history of depression is to understand the invention of human being as we now know and are him. Our Prozac-popping, cognitively focused, semi-alienated postmodernity is only a stage in the ongoing understanding and control of mood and character. (Solomon 2001, 286) ALTHOUGH ANDREW SOLOMON clearly believes that "the shape and detail of depression have gone through a thousand cartwheels," Jennifer Radden gives us pause before assuming that depression is just another name for Dame Melancholy. Solomon's claim depends on a deeper metaphysical claim about the nature of depression and its causes. The current method of psychiatric nosology, descriptivism, does not necessarily support equating melancholia and depression. Furthermore, it appears that adopting descriptivism as the sole method of classifying mental disorders commits us to cultural relativist psychiatry. Below I reconsider whether we want to rule out causal classifications and suggest that embracing both descriptivism and causal classifications offer us greater possibilities in understanding human illness and culture.Although the occasion for Jennifer Radden's essay is to investigate whether or not melancholia and depression refer to the same thing, her essay detours into a consideration of extra-descriptivist models of psychiatric illness versus the descriptivism of current psychiatric nosology. This detour turns out to be warranted; her purely academic question yields to a timelier question concerning the proper methodology for classifying mental disorders. Whereas debates about psychiatric nosology are perennial, the recent success of the new generation of antidepressants [End Page 57] is reviving biological psychiatry and its search for the neurochemical origins of depression. Hence, embedded in Radden's question concerning whether or not melancholia is the same thing as clinical depression, is another important question concerning the causes of mental illness, particularly depression.Currently, with its descriptivist approach, the Diagnostic and Statistical Manual of Mental Disorders (DSM) does not classify mental illness, such as clinical depression, based on underlying causes. The cluster of symptoms and behavioral signs that lead a clinician to diagnose one as depressed that are contained in either the DSM or the International Classification of Diseases (ICD) may be too fuzzy or elusive to give any clear distinction between major depression, mild depression, and the blues. For example, one group of epidemiologists points out that [t]he DSM-III, DSM-III-R, and DSM-IV acknowledge that depression, like many mental disorders, has no currently obvious natural classes... If natural classes of depression exist, then their nosology awaits the discovery of distinct and reliable genetic, biological, clinical, or other predictors of risk, severity, or clinical course. Clinicians have a tradition of separating depressions into subtypes; however, this subtyping has not yet led to clear-cut delineations of syndromes in populations. (Kaelber 1995, 4) The evidence is still insufficient to establish the biological or psychological origins of depression. Although many theories exist that explain why people become depressed, scientifically we are not yet in a position to determine which is the right theory. From a pragmatic perspective, however, whether or not we know what causes depression, we can nonetheless attempt to alleviate suffering from depression. And it is with this goal in mind that the DSM-IV and ICD-10 classify mental disorders.Now, given that our current methodology for psychiatric nosology does not establish causes, it is also insufficient for determining what... (shrink)

The century-old controversy over the reproduction and function of the centriole is examined to elucidate the conceptual and methodological issues that have made it so resistant to closure. The study of centrioles is situated in two distinct eras punctuated by the deployment of the electron microscope. From the late 19th century to the mid-20th century, centrioles were defined largely in functional terms- as self-reproducing 'central bodies' playing a directive role in mitosis. During this period, when their structure remained unknown, their (...) universal presence in all cells was ambiguous, and their reality was seriously debated. A conceptual switch occurred after the mid 1950s. When the centriole was made visible under the electron microscope, it was defined in terms of its characteristic cartwheel structure, but its function and manner of reproduction have remained enigmatic. The controversy over the nature of centrioles illustrates the dynamic interplay of techniques, theories, and background assumptions in the production of scientific knowledge. It also highlights the difficulties biologists face in coming to grips with problems of cell structure and intracellular morphogenesis. (shrink)

Paradoxes are many things. Artificial intelligence views them as viruses of the brain, strange replicators that unexpectedly exploit design possibilities. For the child, they are intellectual cartwheels, an everyday delight. For mathematicians and logicians, they reveal skeletons in the closet of reason. For philosophers and dramatists, they capture the contradictions of experience. The historian of ideas sees that they come in successive waves, surging through Classical Greece, the Renaissance and the twentieth century. Professor Leiber's user-'friendly guide to paradoxes provides an (...) up-to-date survey of an ancient and perennial source of puzzlement. Book jacket. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Weight I Just Can’t LoseShelley Lynn MeyersI have always been a “fat person”. According to the medical definition though, I have not always been obese. I have spent most of my life on a journey from chubby to obese, finally ending at my current “overweight” status. After years of struggling with obesity I had gastric bypass surgery, finally losing enough weight to be “normal.” However, regardless of the (...) number on the scale or the BMI category into which I fell, I was still “fat”. I may have lost weight but I did not lose the experience and memories of life as an obese person. I was a fat girl on the inside.My earliest memories of childhood consist of feeling fat and awkward. I was the kid reading a book, watching other little girls practice their cartwheels and boys play tag. I was the kid who also hated gym class, especially the days we practiced tumbling or had to climb ropes. I heard the other kids laugh when I had difficulty doing these things. It’s no surprise that I was last or next to last when we had to choose teams for sports. At least when we played flag football I could play center and use my weight as an asset, blocking players from the other team.Certainly, taunts about my weight and even my own intrusive condemning thoughts were not constant, but they were frequent. Admittedly, I probably berated myself much more often than my peers did. I hated being different. What saddens me to this very day are promises I would make to God if I only I could be “like everyone else”. Oh the things that I would change, or give up for the gift of being a normal size. Even my good qualities, such as academic achievement, became another characteristic that made me stand out when all I wanted to do was hide amongst the crowd. I would have happily traded the high GPA for a lower number on the scale. [End Page E4]Some memories from that era seem to be forever etched into my mind. It has been more than thirty years since I was in the seventh grade, but I remember one particular incident very clearly. I went to my first school dance and was thrilled that I actually slow danced with a boy that I had liked since the fourth grade, Jeff1*. We danced to “How Much I Feel” by Ambrosia. Jeff wore a plaid flannel shirt, and I remember how soft it felt when I put my arms around his neck. The puppy love joy I felt that night was short-lived. At school the next day I read a note written by a female classmate. She wrote about the dance, saying that she had wanted to dance with Jeff, but “he was dancing with that fat pig”. She included my name as well, so there was no mistaking to whom she was referring. I felt nauseous. I decided that happiness was just a set-up for disappointment.Even though I thinned out somewhat during high school, I was still larger than most of my friends and saw myself as fat. I received few actual comments about my weight but I just knew they were thinking it. My best friends were exceptionally thin (one, I would later find out had an eating disorder), which added to my distorted body image. I also was the “friend”, rather than the “girlfriend”, with boys asking me to introduce them to my skinny friends. I was ecstatic when I had a horrible case of the flu and lost a lot of weight due to vomiting and the inability to keep food down. I remember hoping that I could get the flu every couple of months.I read fashion magazines and studied the latest, greatest ways to lose weight. Diet pills, fad soup diets and low calorie frozen dinners were popular and I tried most of them. Sadly, the very methods I tried to “get skinny” likely put me on the path to obesity. Starving myself just led to unhealthy eating, cravings and quite possibly, a metabolism that had no... (shrink)