Versatile Solid Supports for Oligonucleotide Synthesis that Incorporate Urea Bridge

The universal solid support, USIII, representing a new and improved version of commercial USII, as well as 2 ′-deoxynucleoside and 2 ′-deoxy-2 ′-fluoronucleoside bound supports, incorporating a labile phenoxyacetyl fragment, was synthesized by an aminomethyl polystyrene carbamoylation with corresponding azides in the presence of aqueous triethylammonium bicarbonate. All three solid phases incorporate a stable urea tether, thus bridging the polymer and functional linker. These new matrices proved to be potent solid phases for the synthesis of DNA, RNA, or modified oligonucleotides as well as randomized mixed 2 ′-ribo/2 ′-deoxy-2 ′-fluoro-RNA libraries and/or DNA libraries, randomized with trinucleotides (codons).     

Synthesis of Biotin-Containing Phosphoramidite Linker with Polyether Spacer Arm

A phosphoramidite linker unit, based on glycerol backbone and containing a biotin residue attached through a tetraethylene glycol spacer arm, was synthesized. DMTr-Glycidol and tetraethylene glycol were used as starting materials. After conversion of one of hydroxy groups in tetraethylene glycol into an amino group, the epoxy cycle in DMTr-glycidol was opened by this amino alcohol, resulting in the corresponding ether and some quantity of secondary amine. After attaching of biotin residue to the ether followed by phosphitylation, the desirable linker was obtained. The structure of the linker was confirmed by ¹H-¹H COSY, ¹H-¹³C HSQC, ¹H-¹³C HMBC, ¹H-¹⁵N HSQC, and ¹H-¹⁵N HMBC spectra. The resulted phosphoramidite linker unit is suitable for use in common DNA synthesizers. This approach can be used for preparation of various modifiers containing reporter groups attached to the primary amino function using conventional procedures.     

Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation

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Highlights? Tmem64-deficient mice show increased bone volume ? Tmem64 deficiency reduces [Ca²⁺]_i oscillation in response to RANKL stimulation ? Tmem64 interacts with SERCA2 ? Tmem64 positively regulates osteoclast formation via SERCA2/Ca²⁺ signaling     

Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience

Purpose

Standard treatment for glioblastoma (GBM) is surgery followed by radiation (RT) and temozolomide (TMZ). While there is variability in survival based on several established prognostic factors, the prognostic utility of other factors such as tumor size and location are not well established.

Experimental Design

The charts of ninety two patients with GBM treated with RT at the National Cancer Institute (NCI) between 1998 and 2012 were retrospectively reviewed. Most patients received RT with concurrent and adjuvant TMZ. Topographic locations were classified using preoperative imaging. Gross tumor volumes were contoured using treatment planning systems utilizing both pre-operative and post-operative MR imaging.

Results

At a median follow-up of 18.7 months, the median overall survival (OS) and progression-free survival (PFS) for all patients was 17.9 and 7.6 months. Patients with the smallest tumors had a median OS of 52.3 months compared to 16.3 months among patients with the largest tumors, P = 0.006. The patients who received bevacizumab after recurrence had a median OS of 23.3 months, compared to 16.3 months in patients who did not receive it, P = 0.0284. The median PFS and OS in patients with periventricular tumors was 5.7 and 17.5 months, versus 8.9 and 23.3 months in patients with non-periventricular tumors, P = 0.005.

Conclusions

Survival in our cohort was comparable to the outcome of the defining EORTC-NCIC trial establishing the use of RT+TMZ. This study also identifies several potential prognostic factors that may be useful in stratifying patients.     

Effects of Ramadan upon Fluid and Food Intake,Fatigue, and Physical,Mental, and Social Activities: A Comparison between the UK and Libya

Two studies were performed during Ramadan, one in the UK (N=31) and the other in Libya (N=33). The aims were to assess some changes to lifestyle that are produced by fasting as well as effects due to culture. Subjects were studied on eight separate occasions: four control days (two before and two after Ramadan) and four days during the four weeks of Ramadan itself. A questionnaire was answered that asked about naps and fluid and food intake. The questions elicited if an individual had slept, drank, or eaten, plus the reasons for doing or not doing so. Also, subjects were asked to describe their physical, mental, and social activities, their fatigue, and their perceived abilities to perform physical or mental work. The questionnaire was answered five times per day: at sunrise, at 10:00 h, at 14:00 h, at sunset, and on retiring to sleep at night. Urine samples were collected at sunset and measured for osmolality. Differences between control and Ramadan days, as well as between subjects studied in UK and Libya, were assessed by analysis of variance. Correlations between fatigue and physical, mental, and social activities were also assessed, as were differences in urine osmolality. Fasting during Ramadan resulted in fewer activities and increased fatigue and frequency of napping during daytime. Changes in fluid and food intake indicated some degree of preparation for fasting before sunrise and a marked “recuperation” from fasting after sunset. The reasons given for napping in the daytime, for drinking or not drinking, and for eating or not eating, changed during Ramadan compared with control days; as a result, links between fatigue and activities, and fatigue and fluid and food intake, were all altered during Ramadan, particularly after sunset. Subjects become dehydrated during the daytime, but this was not reduced when females who were menstruating drank during this time. Several differences between the two studies were found. There was a greater frequency of napping during the daytime in the Libya study, and evidence for the conservation of energy during the daytime and reduced physical, mental, and social activities. Subjects' preparations for fasting and recovering from it—their fluid and food intakes and associated reasons for these—also differed. Possible explanations of these differences are discussed. (Author correspondence: waterhouseathome@hotmail.com)