In the trenches: rescue archaeology at the Bala Hissar, Kabul

The Bala Hissar was the royal, military and administrative heart of Kabul for a significant period before itwas occupied by British forces during the first two Anglo-Afghan wars in the nineteenth century. Despite itsarchaeological and historical significance, part of the site continues to function as a military base, an expansionof which began in 2007 when nine large holes were bulldozed into the site before protests halted thework. This paper details the findings of an archaeological impact assessment undertaken in July 2007, andincorporates an analysis of satellite images documenting further construction in 2009. The results provide thefirst explicit archaeological (in particular ceramic) evidence suggesting deep continuity of occupation at thesite. The contested ownership and uncertain future of the Bala Hissar in Kabul exemplify the pressures placedon archaeological sites around the world, in the face of uncontrolled development and competing agendas

Intraventricular Sialidase Administration Enhances GM1 Ganglioside Expression and Is Partially Neuroprotective in a Mouse Model of Parkinson\u27s Disease.

BACKGROUND: Preclinical and clinical studies have previously shown that systemic administration of GM1 ganglioside has neuroprotective and neurorestorative properties in Parkinson\u27s disease (PD) models and in PD patients. However, the clinical development of GM1 for PD has been hampered by its animal origin (GM1 used in previous studies was extracted from bovine brains), limited bioavailability, and limited blood brain barrier penetrance following systemic administration. OBJECTIVE: To assess an alternative therapeutic approach to systemic administration of brain-derived GM1 to enhance GM1 levels in the brain via enzymatic conversion of polysialogangliosides into GM1 and to assess the neuroprotective potential of this approach. METHODS: We used sialidase from Vibrio cholerae (VCS) to convert GD1a, GD1b and GT1b gangliosides to GM1. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. After the first week of infusion, animals received MPTP injections (20 mg/kg, s.c., twice daily, 4 hours apart, for 5 consecutive days) and were euthanized 2 weeks after the last injection. RESULTS: VCS infusion resulted in the expected change in ganglioside expression with a significant increase in GM1 levels. VCS-treated animals showed significant sparing of striatal dopamine (DA) levels and substantia nigra DA neurons following MPTP administration, with the extent of sparing of DA neurons similar to that achieved with systemic GM1 administration. CONCLUSION: The results suggest that enzymatic conversion of polysialogangliosides to GM1 may be a viable treatment strategy for increasing GM1 levels in the brain and exerting a neuroprotective effect on the damaged nigrostriatal DA system

Republican Party doctrine and the West Virginia Coal Mine Wars

The West Virginia Coal Mine Wars of 1912-1913 and 1920-1921 are most strongly associated with the use of government and military force against organized labor. A deeper examination of the contemporary newspapers in the state, associated with the Republican Party reveals the attitudes of the party toward labor. Looking at how these editors reacted to the key events of the mine wars reveals that the Republican Party of the time supported two principles: free enterprise and rule of law. This study shows how the importance of these key principles caused the editors loyal to the party to shift the blame for these strikes from the laborers to the coal companies

Lesioning of the Nucleus of the Hippocampal Commissure Followed by Food Deprivation Stress in Birds Demonstrates Simultaneous Involvement in both the Hypothalamo-Pituitary-Adrenal Axis and the Hypothalamo-Pituitary-Thyroid Axis

The hypothalamo-pituitary-adrenal (HPA) axis is the regulatory system for the neuroendocrine stress response within vertebrates. Within the HPA axis corticotropin releasing hormone (CRH) is a major regulator and driving hormone. A structure named the nucleus of the hippocampal commissure (NHpC) has been found to contain CRH neurons and also these neurons respond to early food deprivation stress significantly prior to the paraventricular nucleus (PVN), the major driving nucleus of the classic neuroendocrine HPA axis. The objective of this study was to perform a knock down of the NHpC via electrolytic lesioning, thus eliminating a significant portion of its population of CRH neurons. An experiment was designed to determine whether the elimination of CRH neurons within the NHpC would have a significant effect on HPA function following exposure of broiler chicks to food deprivation (FD). Male chicks (BW 300-350g, 10-14 d) were used in this experiment and split into 3 groups: 1) Sham surgical controls without FD (SHAM), 2) Sham surgical birds with 2h FD stress (SHAM+FD), and 3) Birds subjected to electrolytic lesioning and 2h FD (LES+FD). Blood, brain and anterior pituitary (APit) were sampled promptly from each bird at 2h of FD for the LES+FD and SHAM+FD groups and intermittently for SHAM CON birds. RT-PCR was performed for gene expression within the NHpC, PVN and anterior pituitary (APit) and a radioimmunoassay was performed to determine plasma corticosterone (CORT) concentrations. All RT-PCR data were analyzed with the Tukey Kramer HSD test and all CORT data were analyzed using one-way ANOVA. Electrolytic lesioning of the NHpC significantly reduced plasma CORT in the LES+FD group compared to intact levels in the SHAM+FD group. Decreased CORT occurred concurrently with decreased amounts of CRH mRNA within the NHpC of the LES + FD group. Supporting this, Proopiomelanocortin heteronuclear RNA (POMC hnRNA) within the APit was significantly downregulated. Interestingly, PVN CRH levels were found to be significantly decreased in the LES+FD group of birds with no lesioning of the PVN itself. Results suggest a possible neural connection from the NHpC to the PVN exists, resulting in down regulation of CRH expression in the PVN. Corticotropin releasing hormone receptor 2 (CRHR2) was found to be significantly downregulated within the PVN and APit in the LES+FD group of birds. Thyroid stimulating hormone beta (TSHβ) was also downregulated along with CRHR2 in the PVN and APit suggesting that CRHR2 expression within the PVN could be an important part of the hypothalamo-pituitary-thyroid (HPT) axis. In conclusion, lesioning the NHpC had a significant effect on the HPA axis. CRH neurons within the NHpC and/or PVN had a significant effect on the HPA and/or HPT axes

Development and Assessment of a Diagnostic DNA Oligonucleotide Microarray for Detection and Typing of Meningitis-Associated Bacterial Species.

Meningitis is commonly caused by infection with a variety of bacterial or viral pathogens. Acute bacterial meningitis (ABM) can cause severe disease, which can progress rapidly to a critical life-threatening condition. Rapid diagnosis of ABM is critical, as this is most commonly associated with severe sequelae with associated high mortality and morbidity rates compared to viral meningitis, which is less severe and self-limiting. We have designed a microarray for detection and diagnosis of ABM. This has been validated using randomly amplified DNA targets (RADT), comparing buffers with or without formamide, in glass slide format or on the Alere ArrayTubeTM (Alere Technologies GmbH) microarray platform. Pathogen-specific signals were observed using purified bacterial nucleic acids and to a lesser extent using patient cerebral spinal fluid (CSF) samples, with some technical issues observed using RADT and glass slides. Repurposing the array onto the Alere ArrayTubeTM platform and using a targeted amplification system increased specific and reduced nonspecific hybridization signals using both pathogen nucleic and patient CSF DNA targets, better revealing pathogen-specific signals although sensitivity was still reduced in the latter. This diagnostic microarray is useful as a laboratory diagnostic tool for species and strain designation for ABM, rather than for primary diagnosis

Short- and Long-Term Complications of Free Anterolateral Thigh Flap Reconstructions: A Single-Centre Experience of 92 Consecutive Cases.

Background The anterolateral thigh (ALT) flap has been amongst the most versatile components of the reconstructive surgeon's armamentarium. The authors utilise these flaps for a variety of reconstructive procedures including lower limb reconstruction; postsarcoma excision; and open fractures. Few studies have discussed the extent of recipient site morbidity and subsequent revisional procedures. We will report our experience of the ALT flap in 92 consecutive reconstructions with focus on recipient site complications and revisional procedures. Methods Retrospective data collection was done from 92 patients who underwent ALT flap reconstruction-for various large soft tissue defects-at our unit at the Royal Free Hospital, London. We evaluated primary recipient site complications and the requirements for secondary operations after flap transfer. Results All flaps survived with the exception of 3 cases (97% survival rate) in which irreversible venous thrombosis was encountered. 16 of 92 patients (17%) required a second recipient site operation for the following: 7 patients experienced major recipient site complications that warranted early return to theatre and 9 patients required a secondary revision thinning procedure(s). 8 of the 16 patients (50%) requiring second operations had construction on their lower leg/ankle/feet (p value = 0.10). Conclusions Our data demonstrated effective use of the ALT flap in the management of soft tissue reconstructive surgery. Partial flap necrosis was the main complication at the recipient site. In future work, secondary thinning procedures, particularly at the ankle/foot, should be separated from flap-specific complications. Furthermore, we demonstrate tailoring ALT thickness can be performed safely without compromising flap viability

Uninterrupted translation through putative 12-nucleotide coding gap in sequence of carA: business as usual

Journal ArticlePrevious work of others reported an untranslated stretch of 12 nucleotides in the 5' coding sequence of carA from Pseudomonas aeruginosa. However, N-terminal protein sequencing of carA-lacZ translational fusions shows that these 12 nucleotides are normally translated in a continuous triplet manner, both in P. aeruginosa and in Escherichia coli