Coordinating development: uncovering the mechanisms that coordinate organ growth and patterning with the development of the whole body

Organisms produce correctly patterned structures across a wide range of organ and body sizes. Despite considerable work revealing the mechanisms that regulate the growth and patterning of organs, those responsible for coordinating organ development with whole-body development are still largely unknown.(...)

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study

Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.

Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans

OBJECTIVE: Lipids stored in adipose tissue can originate from dietary lipids or from de novo lipogenesis (DNL) from carbohydrates. Whether DNL is abnormal in adipose tissue of overweight individuals remains unknown. The present study was undertaken to assess the effect of carbohydrate overfeeding on glucose-induced whole body DNL and adipose tissue lipogenic gene expression in lean and overweight humans. DESIGN: Prospective, cross-over study. SUBJECTS AND METHODS: A total of 11 lean (five male, six female, mean BMI 21.0+/-0.5 kg/m(2)) and eight overweight (four males, four females, mean BMI 30.1+/-0.6 kg/m(2)) volunteers were studied on two occasions. On one occasion, they received an isoenergetic diet containing 50% carbohydrate for 4 days prior to testing; on the other, they received a hyperenergetic diet (175% energy requirements) containing 71% carbohydrates. After each period of 4 days of controlled diet, they were studied over 6 h after having received 3.25 g glucose/kg fat free mass. Whole body glucose oxidation and net DNL were monitored by means of indirect calorimetry. An adipose tissue biopsy was obtained at the end of this 6-h period and the levels of SREBP-1c, acetyl CoA carboxylase, and fatty acid synthase mRNA were measured by real-time PCR. RESULTS: After isocaloric feeding, whole body net DNL amounted to 35+/-9 mg/kg fat free mass/5 h in lean subjects and to 49+/-3 mg/kg fat free mass/5 h in overweight subjects over the 5 h following glucose ingestion. These figures increased (P<0.001) to 156+/-21 mg/kg fat free mass/5 h in lean and 64+/-11 mg/kg fat free mass/5 h (P<0.05 vs lean) in overweight subjects after carbohydrate overfeeding. Whole body DNL after overfeeding was lower (P<0.001) and glycogen synthesis was higher (P<0.001) in overweight than in normal subjects. Adipose tissue SREBP-1c mRNA increased by 25% in overweight and by 43% in lean subjects (P<0.05) after carbohydrate overfeeding, whereas fatty acid synthase mRNA increased by 66 and 84% (P<0.05). CONCLUSION: Whole body net DNL is not increased during carbohydrate overfeeding in overweight individuals. Stimulation of adipose lipogenic enzymes is also not higher in overweight subjects. Carbohydrate overfeeding does not stimulate whole body net DNL nor expression of lipogenic enzymes in adipose tissue to a larger extent in overweight than lean subjects.

Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels.

Chronic disorders, such as obesity, diabetes, inflammation, non-alcoholic fatty liver disease and atherosclerosis, are related to alterations in lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPAR)α, PPARβ/δ and PPARγ are involved. These receptors form a subgroup of ligand-activated transcription factors that belong to the nuclear hormone receptor family. This review discusses a selection of novel PPAR functions identified during the last few years. The PPARs regulate processes that are essential for the maintenance of pregnancy and embryonic development. Newly found hepatic functions of PPARα are the mediation of female-specific gene repression and the protection of the liver from oestrogen induced toxicity. PPARα also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPARγ controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes. Activation of PPARβ/δ increases lipid catabolism in skeletal muscle, the heart and adipose tissue. In addition, PPARβ/δ ligands prevent weight gain and suppress macrophage derived inflammation. In fact, therapeutic benefits of PPAR ligands have been confirmed in inflammatory and autoimmune diseases, such as encephalomyelitis and inflammatory bowel disease. Furthermore, PPARs promote skin wound repair. PPARα favours skin healing during the inflammatory phase that follows injury, whilst PPARβ/δ enhances keratinocyte survival and migration. Due to their collective functions in skin, PPARs represent a major research target for our understanding of many skin diseases. Taken altogether, these functions suggest that PPARs serve as physiological sensors in different stress situations and remain valuable targets for innovative therapies.

Skeletal muscle fibre-type comparison of whole tissue and subcellular membrane phospholipids and fatty acids

Membranes are dynamic structures that affect cell structure and function. Compositional changes ofmembranes have been shown with the application of a perturbation; however these are limited to whole tissue analysis. The purpose of this thesis was to compare the phospholipid (PL) fatty acid (FA) composition of rat whole muscle (Wm) to 1) purified and non-purified subsarcolemmal (SS) mitochondria in soleus, plantaris, and red gastrocnemius, and 2) sarcolemma, transverse-tubules, SS and intermyofibrillar (IMF) mitochondria fix)m whole hindlimb. The major findings were that 1) contamination significantly altered the PL FA composition of the SS mitochondrial membrane fraction, 2) Wm and SS mitochondria compositions differed between muscle types, and 3) Wm did not accurately reflect the PL FA composition of any isolated subcellular membranes, with each being unique from each other. As such, the relevancy of the trends reported in the literature of the effects of perturbations on Wm may be limited.

Pollen and grain size records in abyssal sediments of the northwest Pacific Ocean as proxies of Plio-Pleistocene climate change /

A distinctive period of global change occurred during the PUocene between the warm Miocene and subsequent Quaternary cooling. Samples from Ocean Drilling Project Site 11 79 (-5586 mbsl, 41°4'N, 159°57'E), Site 881 (-5765 mbsl, 47°6.133'N, 161°29.490'E) and Site 882 (-3255 mbsl, 50°22'N, 167°36'E) were studied to determine the magnitude and composition ofterrigenous flux to the western mid-latitude North Pacific and its relation to climate change in East Asia since the mid-Pliocene. Dust-sized particles (including pollen), sourced from the arid regions and loess plateaus in East Asia are entrained by prevailing westerly winds and transported to the midlatitude northwest North Pacific Ocean. This is recorded by peaks in the total concentration of pollen and spores, as well as the mean grain size of allochthonous and autochthonous silicate material in abyssal marine sediments. Aridification of the Asian interior due to the phased uplift of the Himalayan-Tibetan Plateau created the modem East Asian Monsoon system dominated by a strengthening of the winter monsoon. The winter monsoon is further enhanced during glacials due to the expansion of desert and steppe environments at the expense ofwoodlands and forests recorded by the composition of palynological assemblages. The late Pliocene-Pleistocene glacials at ODP Sites 1 179, 881, and 882 are characterized by increases in grain size, magnetic susceptibility, pollen and spore concentrations around 3.5-3.3, 2.6-2.4, 1.7-1.6, and 0.9-0.7 Ma (ages based on magnetostratigraphic and biostratigraphic datums). The peaks during these times are relatively rich in pollen taxa derived primarily from steppe and boreal vegetation zones, recording cool, dry climates. The overall size increase of sediment and abundance of terrestrial palynomorphs record enhanced wind strength. The increase in magnitude of pollen and spore concentrations as well as grain size record global cooling and Northern Hemisphere glaciation. The peaks in grain size as well as pollen and spore abundance in marine sediments correlate with the mean grain size of loess in East Asia, consistent with the deflation of unarmoured surfaces during glacials. The transport of limiting nutrients to marine environments enhanced sea surface productivity and increased the rate of sediment accumulation.

Spelling performance of third grade students : a comparison of whole-language-plus-strategy instruction, strategy instruction only, and the whole language approach

This study investigated three methods for teaching children how to spell. Third grade students were divided into three conditions for a one-week training period consisting of 15- to 20-minute lessons. One of the two experimental conditions used a whole language approach along with explicit strategy instruction. The second condition used strategy instruction within a traditional setting. The control used strictly a whole language approach to le~ing hO\\l to spell. The spelling perfonnance of all three conditions improved after the one-week training period. However, students in the strategy instruction groups did significantly better on the study "'7ords than the whole language only group. The students in whole-Ianguage-plusstrateg)! instruction outperformed both other groups. Significantly better spelling perfonnance was observed even at the nine-week posttest. This study frrst supported the hypothesis that children can make significantly greater improven1ents in their spelling when explicitly taught how to use spelling strategies. Secondl)', this study indicated that whole language provided a relevant context for the study words, clearly giving the students in the whole-Ianguage-plus-strategy condition an additional advantage.

The measurement of the optical absorption cross section of photosystem 1 and photosystem 2 from whole live cells of porphyridium cruentum, in light state 1 and light state 2

The optical cross section of PS I in whole cells of Porphyridium cruentum (UTEX 161), held in either state 1 or state 2, was determined by measuring the change in absorbance at 820nm, an indication of P700+; the X-section of PS2 was determined by measuring the variable fluorescence, (Fv-Fo)/Fo, from PS2. Both cross-sections were 7 determined by fitting Poisson distribution equations to the light saturation curves obtained with single turnover laser flashes which varied in intensity from zero to a level where maximum yield occurred. Flash wavelengths of 574nm, 626nm, and 668nm were used, energy absorbed by PBS, by PBS and chla, and by chla respectively. There were two populations of both PSi and PS2. A fraction of PSi is associated with PBS, and a fraction of PS2 is free from PBS. On the transition S1->S2, only with PBS-absorbed energy (574nm) did the average X-section of PSi increase (27%), and that of PS2 decrease (40%). The fraction of PSi associated with PBS decreased, from 0.65 to 0.35, and the Xsection of this associated PS 1 increased, from 135±65 A2 to 400±300A2. The cross section of PS2 associated with PBS decreased from 150±50 A2 to 85±45 A2, but the fraction of PS2 associated with PBS, approximately 0.75, did not change significantly. The increase in PSi cross section could not be completely accounted for by postulating that several PSi are associated with a single PBS and that in the transition to state2, fewer PSi share the same number of PBS, resulting in a larger X-section. It is postulated that small changes occur in the attachment of PS2 to PBS causing energy to be diverted to the attached PSi. These experiments support neither the mobile-PBS model of state transitions nor that of spillover. From cross section changes there was no evidence of energy transfer from PS2 to PSi with 668nm light. The decrease in PS2 fluorescence which occurred at this wavelength cannot be explained by energy transfer; another explanation must be sought. No explanation was found for an observed decrease in PSi yield at high flash intensities.

Every man his own guide to the Falls of Niagara : or, The whole story in a few words /

Cover title: Guide to Niagara Falls.

"The whole earth as village" : a chronotopic analysis of Marshall McLuhan's "Global Village" and Patrick McGoohan's The Prisoner

Marshall McLuhan's "global village", and his theories on communications and technology, in conjunction with Patrick McGoohan's television series The Prisoner (ATV, 1967-1968) are explored in this thesis. The Prisoner, brainchild of McGoohan, is about the abduction and confinement of a British government agent imprisoned within the impenetrable boundaries of a benign but totalitarian city -state called "The Village". The purpose of his abduction and imprisonment is for the extraction of information regarding his resignation as a government spy. Marshall McLuhan originally popularized the phrase "the global village" in The Gutenberg Galaxy: The Making o/the Topographic Man (1962), asserting that, "The new electronic interdependence recreates the world in the image of a global village" (p. 31). This thesis argues that valid parallels exist between McGoohan's conception of "village", as manifested in The Prisoner, and McLuhan's global village. The comprehensive methodological stratagem for this thesis includes Marshall McLuhan's "mosaic" approach, Mikhail Bakhtin's concept ofthe "chronotope", as well as a Foucauldian genealogicallhistorical discourse analysis. In the process of deconstructing McLuhan's texts and The Prisoner as products of the 1960s, an historical "constellation" (to use Walter Benjamin's concept) of the same present has been executed. By employing this synthesized methodology, conjunctions have been made between McLuhan's theories and the series' main themes of bureaucracy as dictatorship, the perversion of science and technology, freedom as illusion, and the individual in opposition to the collective. A thorough investigation of the global village and The Prisoner will determine whether or not Marshall McLuhan and/or Patrick McGoohan visualize the village as an enslaving technological reality.

The effects of an acute bout of whole-body vibration on pulse wave velocity in individuals with SCI

Cardiovascular disease is a leading cause of mortality in the spinal cord injured (SCI) population. Reduced arterial compliance is a cardiovascular risk factor and whole body vibration (WBV) has be en shown to improve arterial compliance in able-bodied individuals. The study investigated the effect of an acute session ofWBV on arterial compliance as measured by pulse wave velocity (PWV). On separate days, arm, leg and aortic PWV were measured pre- and post- a 45 minute session of passive stance (PS) and WBV. The WBV was intermittent with a set frequency of 45Hz and amplitude of O.6mm. There was no condition by time effect when comparing PWV after WBV and PS. Following WBV, aortic (928.6±127.7 vs. 901.1±96.6cm/sec), leg (1035.2±113.8 vs.l099.8±114.2cm/sec) and arm PWV (1118.9±119.8 vs. 1181.1±124.4cm/s) did not change. As such, WBV did not reduce arterial compliance, however future research with protocol modifications is recommended.

The Weekly Register Vol. III, No. 11, Whole No. 63- November 14,1812

The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. This issue is part of a bound book titled the Weekly Register 1812-1814. Pages are divided as follows: November 14, 1812- Pages 161-174 January 22, 1814- Pages 337-352 July 30, 1814- Pages 361-376 Look for other issues of the Weekly Register within the website.