FACKEL is a sterol C-14 reductase required for organized cell division and expansion in Arabidopsis embryogenesis

In flowering plants, the developing embryo consists of growing populations of cells whose fates are determined in a position-dependent manner to form the adult organism. Mutations in the FACKEL (FK) gene affect body organization of the Arabidopsis seedling. We report that FK is required for cell division and expansion and is involved in proper organization of the embryo. We isolated FK by positional cloning. Expression analysis in embryos revealed that FK mRNA becomes localized to meristematic zones. FK encodes a predicted integral membrane protein related to the vertebrate lamin B receptor and sterol reductases across species, including yeast sterol C-14 reductase ERG24. We provide functional evidence that FK encodes a sterol C-14 reductase by complementation of erg24. GC/MS analysis confirmed that fk mutations lead to accumulation of intermediates in the biosynthetic pathway preceding the C-14 reductase step. Although fk represents a sterol biosynthetic mutant, the phenotype was not rescued by feeding with brassinosteroids (BRs), the only plant sterol signaling molecules known so far. We propose that synthesis of sterol signals in addition to BRs is important in mediating regulated cell growth and organization during embryonic development. Our results indicate a novel role for sterols in the embryogenesis of plants

Fertility Ideals of Women and Men Across the Life Course

This paper explores the stability of women’s and men’s fertility preferences across the life course. The data come from the first six waves of the German Family Panel (pairfam), which span the period from 2008/2009 until 2013/2014. In our analysis, fertility preferences are measured using the following question: “Under ideal circumstances, how many children would you like to have?” The average number cited by both women and men is 2.2. With rising age, this number declines modestly. Relying on fixed-effects modelling, we find that neither partnership status nor economic circumstances have any causal effect on fertility preferences. However, as the number of children a respondent has increases, his or her ideal number of children is also likely to grow. Thus, fertility ideals appear to undergo changes over time, and are adjusted in line with the size of the respondent’s own family

3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing

BACKGROUND: To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT) performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures. MATERIALS AND METHODS: 39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomittant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax (® )and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22). Later the dose distribution was calculated with KonRad (® )and fluence was modified by MCP 96 alloy compensators (n = 17). Gross tumor/tumor bed (PTV 1) was irradiated up to 60–70 Gy, [5 fractions/week, single fraction dose: 2.0–2.2 (simultaneously integrated boost)], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2) with 48–54 Gy [single dose: 1.5–1.8]). Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ). RESULTS: Mean of the median doses at the parotid glands to be spared was 25.9 (16.3–46.8) Gy, for tin graulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (°0–2/3): xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed °0–2/3): 88%/12%. 6 months postRT chronic xerostomia °0–2/3 was observed in 85%/15% of patients, none with °4 xerostomia. CONCLUSION: 3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced head and neck cancers. Since the concept of lower single (and total) doses in the adjuvantly treated volumes reduces acute morbidity 3D-c-IMRT nicely meets demands of concurrent chemotherapy protocols

Effects of conjugated linoleic acid on myogenic and inflammatory responses in a human primary muscle and tumor coculture model

The antiproliferative and anti-inflammatory properties of conjugated linoleic acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle wasting disease, particularly cancer cachexia. Human primary muscle cells were grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD, myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF-) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11 isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%. There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%, respectively), but no change in either Myf5 or myostatin, in myotubes grown in coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A similar pattern of myogenic gene expression changes was observed in myotubes treated with TNF- alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF- expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF- in myotubes and could ameliorate its tumor-induced rise. The study provides insight into the anti-inflammatory and antiproliferative actions of CLA and its application as a therapeutic agent in inflammatory disease states.<br /

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition

Foraminiferal assemblages as palaeoenvironmental bioindicators in Late Jurassic epicontinental platforms: relation with trophic conditions

Foraminiferal assemblages from the neritic environment reveal the palaeoecological impact of nutrient types in relation to shore distance and sedimentary setting. Comparatively proximal siliciclastic settings from the Boreal Domain (Brora section, Eastern Scotland) were dominated by inner−shelf primary production in the water column or in sea bottom, while in relatively seawards mixed carbonate−siliciclastic settings from the Western Tethys (Prebetic, Southern Spain), nutrients mainly derived from the inner−shelf source. In both settings, benthic foraminiferal assemblages increased in diversity and proportion of epifauna from eutrophic to oligotrophic conditions. The proximal setting example (Brora Brick Clay Mb.) corresponds to Callovian offshore shelf deposits with a high primary productivity, bottom accumulation of organic matter, and a reduced sedimentation rate for siliciclastics. Eutrophic conditions favoured some infaunal foraminifera. Lately, inner shelf to shoreface transition areas (Fascally Siltstone Mb.), show higher sedimentation rates and turbidity, reducing euphotic−zone range depths and primary production, and then deposits with a lower organic matter content (high−mesotrophic conditions). This determined less agglutinated infaunal foraminifera content and increasing calcitic and aragonitic epifauna, and calcitic opportunists (i.e., Lenticulina). The comparatively distal setting of the Oxfordian example (Prebetic) corresponds to: (i) outer−shelf areas with lower nutrient input (relative oligotrophy) and organic matter accumulation on comparatively firmer substrates (lumpy lithofacies group) showing dominance of calcitic epifaunal foraminifera, and (ii) mid−shelf areas with a higher sedimentation rate and nutrient influx (low−mesotrophic conditions) favouring potentially deep infaunal foraminifers in comparatively unconsolidated and nutrient−rich substrates controlled by instable redox boundary (marl−limestone rhythmite lithofacies).This research was carried out with the financial support of projects CGL2005−06636−C0201 and CGL2005−01316/BTE, and University of Oslo, Norway−Statoil cooperation. M.R. holds a Juan de la Cierva grant from the Ministry of Science and Technology of Spain