Heparan Sulfate Regulates Hair Follicle and Sebaceous Gland Morphogenesis and Homeostasis

Hair follicle (HF) morphogenesis and cycling are a result of intricate autonomous epithelial-mesenchymal interactions. Once the first HF cycle is complete it repeatedly undergoes cyclic transformations. Heparan sulfate (HS) proteoglycans are found on the cell surface and in the extracellular matrix where they influence a variety of biological processes by interacting with physiologically important proteins, such as growth factors. Inhibition of heparanase (an HS endoglycosidase) in in vitro cultured HFs has been shown to induce a catagen-like process. Therefore, this study aimed to elucidate the precise role of HS in HF morphogenesis and cycling. An inducible tetratransgenic mouse model was generated to excise exostosin glycosyltransferase 1 (Ext1) in keratin 14-positive cells from P21. Interestingly, EXT1^{StEpiΔ/StEpiΔ} mice presented solely anagen HFs. Moreover, waxing the fur to synchronize the HFs revealed accelerated hair regrowth in the EXT1^{StEpiΔ/StEpiΔ} mice and hindered cycling into catagen. The ablation of HS in the interfollicular epidermal cells of mature skin led to the spontaneous formation of new HFs and an increase in Sonic Hedgehog expression resembling wild-type mice at P0, thereby indicating that the HS/Sonic Hedgehog signaling pathway regulates HF formation during embryogenesis and prevents HF formation in mature skin. Finally, the knock-out of HS also led to the morphogenesis and hyperplasia of sebaceous glands and sweat glands in mature mice, leading to exacerbated sebum production and accumulation on the skin surface. Therefore, our findings clearly show that an intricate control of HS levels is required for HF, sebaceous gland, and sweat gland morphogenesis and HF cycling.     

The Influence of Diabetic Peripheral Neuropathy on Local Postural Muscle and Central Sensory Feedback Balance Control

Poor balance control and increased fall risk have been reported in people with diabetic peripheral neuropathy (DPN). Traditional body sway measures are unable to describe underlying postural control mechanism. In the current study, we used stabilogram diffusion analysis to examine the mechanism under which balance is altered in DPN patients under local-control (postural muscle control) and central-control (postural control using sensory cueing). DPN patients and healthy age-matched adults over 55 years performed two 15-second Romberg balance trials. Center of gravity sway was measured using a motion tracker system based on wearable inertial sensors, and used to derive body sway and local/central control balance parameters. Eighteen DPN patients (age = 65.4±7.6 years; BMI = 29.3±5.3 kg/m²) and 18 age-matched healthy controls (age = 69.8±2.9; BMI = 27.0±4.1 kg/m²) with no major mobility disorder were recruited. The rate of sway within local-control was significantly higher in the DPN group by 49% (healthy local-control_slope = 1.23±1.06×10^-2 cm²/sec, P<0.01), which suggests a compromised local-control balance behavior in DPN patients. Unlike local-control, the rate of sway within central-control was 60% smaller in the DPN group (healthy central-control_slope-Log = 0.39±0.23, P<0.02), which suggests an adaptation mechanism to reduce the overall body sway in DPN patients. Interestingly, significant negative correlations were observed between central-control rate of sway with neuropathy severity (r _Pearson = 0.65-085, P<0.05) and the history of diabetes (r _Pearson = 0.58-071, P<0.05). Results suggest that in the lack of sensory feedback cueing, DPN participants were highly unstable compared to controls. However, as soon as they perceived the magnitude of sway using sensory feedback, they chose a high rigid postural control strategy, probably due to high concerns for fall, which may increase the energy cost during extended period of standing; the adaptation mechanism using sensory feedback depends on the level of neuropathy and the history of diabetes.     

Inv(10)(p11.2q21.2), a variant chromosome

We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome 10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status is not warranted in view of the unnecessary concern this may cause parents and other family members. Received: 7 July 1997 / Accepted: 4 August 1997     

The Proverbial Bourdieu: Habitus and the Politics of Representation in the Ethnography of Kabylia

Since the 1970s, anthropologists have been centrally concerned with the relationship of ethnographic representation to political and historical context. Interestingly, the work of Pierre Bourdieu has largely escaped such contextualization, despite the significance of Bourdieu's ideas to anthropological theorizing. Today, many of Bourdieu's central concepts float free from the context out of which they arose—the Kabyle region of Algeria. This article addresses this omission by reading Bourdieu's early works against each other to reconstitute aspects of his methodology and fieldwork. Focusing on his choice to represent the Kabyles of his early work in prose, and those in his later work via proverbs, I suggest that key premises of Bourdieu's theory may not be supported by historical and ethnographic evidence. I consider how Bourdieu's position as a young social scientist grappling with ethnographic responsibilities in colonial wartime led him to privilege his interlocutors' accounts in some studies while expunging them from others. [Keywords: Bourdieu, represented speech, literacy, Algeria, Berbers]     

Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors

Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.