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A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICE Ml Sym ᴿ⁷ᴬ is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS . Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171 , producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses indicated that the PRF occurred through +1 slippage of the tRNA ᵖʰᵉ from UUU to UUC within a conserved msi172 -encoded motif. FseA activated rdfS expression in the absence of ICE Ml Sym ᴿ⁷ᴬ, suggesting that it directly activated rdfS transcription, despite being unrelated to any characterized DNA-binding proteins. Bacterial two-hybrid and gene-reporter assays demonstrated that FseA was also bound and inhibited by the ICE Ml Sym ᴿ⁷ᴬ-encoded quorum-sensing antiactivator QseM. Thus, activation of ICE Ml Sym ᴿ⁷ᴬ excision is counteracted by TraR antiactivation, ribosomal frameshifting, and FseA antiactivation. This robust suppression likely dampens the inherent biological noise present in the quorum-sensing autoinduction circuit and ensures that ICE Ml Sym ᴿ⁷ᴬ transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICE Ml Sym ᴿ⁷ᴬ transfer regulatory system provides an example of how a set of modular components have assembled through evolution to form a robust genetic toggle that regulates gene transcription and translation at both single-cell and cell-population levels. Significance Integrative and conjugative elements (ICEs) facilitate horizontal transfer of multiple genetic determinants. Here we show that a programmed ribosomal frameshift (PRF) contributes to the regulation of ICE transfer. The low-frequency PRF fuses the coding sequences of two genes, resulting in a single-protein Frameshifted excision activator (FseA) that activates ICE excision. An antiactivator, QseM, known to disrupt the quorum-sensing regulator TraR, also disrupted FseA. The evolved PRF site, together with the dual-target antiactivator, QseM, likely provides robust suppression of ICE transfer in the face of the inherent biological noise of quorum-sensing autoinduction. This work illustrates how a complex multipartite regulatory system has assembled through evolution to form a robust genetic toggle to control gene transcription and translation at both single-cell and cell-population levels.

This study reviews the campaigns and battles of the Sixth Century A. D. Byzantine General Belisarius, attempting to extract common threads of military thought and principles and providing an analysis as to the application of his method to today's military operations. Belisarius won extraordinary victories on three continents, often fighting against overwhelming odds. The study reviews the world environment from the perspective of the Eastern Roman Empire along with the major personalities of the age. After a short review of the Eastern Roman Empire's military structure, the study reviews chronologically, and analyzes Belisarius' campaigns against the Persians, the Vandals, and the Ostrogoths. This study concludes showing that mastership of strategic and tactical thought, deception, psychological warfare, superior technology and training, and elite forces were among the keys of Belisarius success. Finally, these keys of success are related to modern day military operations.

Despite similar strategic and procurement interests, defense contracting practices vary between the United States and Australia. This comparative article discusses how both countries approach termination for convenience (TFC) in defense contracts, ultimately arguing that the use of TFC clauses in U.S. government contracts is exercised too broadly. Minor, but impactful, reform is posited based on Australia’s approach. Limiting the exercise of a TFC clause to times of exigency, or where performance of the contract is no longer practicable, is likely to limit a contractor’s risk associated with fulfillment of a government contract, minimize policy harms and could serve to bolster the government’s position in the commercial marketplace.

The Army Transformation is highly visible at Fort Lewis WA, and no more so than with the engineers. Wright discusses how this transformation can be seen through the structure, equipment, and training at Fort Lewis.

With a median follow-up of 13 years, a randomized comparison of radiotherapy with or without antiandrogen therapy in patients with a rising PSA level after prostatectomy showed that 2 years of antiandrogen therapy resulted in a significantly higher overall survival rate. Patients with localized prostatic cancer are often treated with radical prostatectomy. More than 30% of such patients will subsequently have recurrence. This recurrence manifests first as a rising serum level of prostate-specific antigen (PSA), 1 – 3 termed biochemical recurrence. Large, retrospective studies suggest that salvage radiation therapy after biochemical recurrence may be associated with long-term freedom from cancer recurrence. 4 , 5 However, 50% of the patients who are treated with salvage radiation therapy will have further disease progression, particularly when there are aggressive disease features. 4 – 7 The combination of radiation therapy and either androgen-deprivation therapy or antiandrogen therapy prolongs survival among some . . .

In a trial in patients with pelvic or acetabular fractures or extremity fractures that were treated operatively, aspirin thromboprophylaxis was noninferior to low-molecular-weight heparin in preventing death at 90 days.