Retention of function without normal disc morphogenesis occurs in cone but not rod photoreceptors

It is commonly assumed that photoreceptor (PR) outer segment (OS) morphogenesis is reliant upon the presence of peripherin/rds, hereafter termed Rds. In this study, we demonstrate a differential requirement of Rds during rod and cone OS morphogenesis. In the absence of this PR-specific protein, rods do not form OSs and enter apoptosis, whereas cone PRs develop atypical OSs and are viable. Such OSs consist of dysmorphic membranous structures devoid of lamellae. These tubular OSs lack any stacked lamellae and have reduced phototransduction efficiency. The loss of Rds only appears to affect the shape of the OS, as the inner segment and connecting cilium remain intact. Furthermore, these structures fail to associate with the specialized extracellular matrix that surrounds cones, suggesting that Rds itself or normal OS formation is required for this interaction. This study provides novel insight into the distinct role of Rds in the OS development of rods and cones

Who owns the diamonds? The occult eco-nomy of diamond mining in Sierra Leone

Much of the literature on Sierra Leonean diamonds focuses on the role that this mineral resource played in the recent civil conflict (1991–2002). However, the political-economic perspective that is common to these analyses has lost sight of the main actors in this social reality. What do miners think of diamonds? Like their Malagasy colleagues engaged in the search for sapphires, the Sierra Leonean diamond miners often maintain that they do not know what diamonds could possibly be used for. What is specific to the diamond mining areas in this West African country is that suspicions and fantasies about the uses of diamonds go hand in hand with the idea that these precious stones belong to invisible spiritual entities known locally as djinns or dεbul dεn. Although this article aims to analyse the occult imaginary of diamond miners, it takes a different stand from the occult economies approach. By combining a historical-imaginative perspective with a historical and ecological one, this article intends to highlight the indissoluble interweaving of material and imaginative processes of artisanal diamond production in the context of Sierra Leone's mines

God’s gifts: destiny, poverty, and temporality in the mines of Sierra Leone

In Sierra Leone, many artisanal miners share the view that every human act and every event is the realisation of an inscrutable divine plan. Even though notions of fate and destiny are part of the vocabulary of Krio, the country’s lingua franca, miners prefer to use expressions that evoke God and stress His immanent presence and influence in their everyday lives. In order to understand the religious vocabulary of contingency and the cosmology underlying the ways in which miners interpret, reproduce, and imaginatively prepare the conditions to change their lives, this article focuses on the ritual practices connected to artisanal diamond mining. It considers these rituals as attempts to resolve the ever-present temporal and moral tensions between actual conditions of suffering and poverty, and the realisation of the well-being that miners associate with their desired futures

A Partial Structural and Functional Rescue of a Retinitis Pigmentosa Model with Compacted DNA Nanoparticles

Previously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the wild-type retinal degeneration slow (Rds) gene were injected into the subretinal space of rds+/− mice on postnatal day 5. Gene expression was sustained for up to four months at levels up to four times higher than in controls injected with saline or naked DNA. The nanoparticles were taken up into virtually all photoreceptors and mediated significant structural and biochemical rescue of the disease without histological or functional evidence of toxicity. Electroretinogram recordings showed that nanoparticle-mediated gene transfer restored cone function to a near-normal level in contrast to transfer of naked plasmid DNA. Rod function was also improved. These findings demonstrate that compacted DNA nanoparticles represent a viable option for development of gene-based interventions for ocular diseases and obviate major barriers commonly encountered with non-viral based therapies

MPI-Ding reference glasses for in situ microanalysis: New reference values for element concentrations and isotope ratios

We present new analytical data of major and trace elements for the geological MPI-DING glasses KL2-G, ML3B-G, StHs6/80-G, GOR128-G, GOR132-G, BM90/21-G, T1-G, and ATHO-G. Different analytical methods were used to obtain a large spectrum of major and trace element data, in particular, EPMA, SIMS, LA-ICPMS, and isotope dilution by TIMS and ICPMS. Altogether, more than 60 qualified geochemical laboratories worldwide contributed to the analyses, allowing us to present new reference and information values and their uncertainties (at 95% confidence level) for up to 74 elements. We complied with the recommendations for the certification of geological reference materials by the International Association of Geoanalysts (IAG). The reference values were derived from the results of 16 independent techniques, including definitive (isotope dilution) and comparative bulk (e.g., INAA, ICPMS, SSMS) and microanalytical (e.g., LA-ICPMS, SIMS, EPMA) methods. Agreement between two or more independent methods and the use of definitive methods provided traceability to the fullest extent possible. We also present new and recently published data for the isotopic compositions of H, B, Li, O, Ca, Sr, Nd, Hf, and Pb. The results were mainly obtained by high-precision bulk techniques, such as TIMS and MC-ICPMS. In addition, LA-ICPMS and SIMS isotope data of B, Li, and Pb are presented

Preliminary Evidence for Limbic-Frontal Hyperexcitability in Psychogenic Nonepileptic Seizure Patients

OBJECTIVES: The goal of the current pilot project was to probe the resting-state magnetoencephalography (MEG) in individuals with psychogenic nonepileptic seizures (PNES) and ascertain if there is evidence for frontal temporal cortical hyperexcitability, as evidenced by increased focal coherence in these regions. METHODS: Six patients with PNES and without any evidence of epilepsy were included. Nine healthy control (HC) subjects (age matched as a group) were also included. Subjects underwent 10 minutes of eyes open and 10 minutes of eyes closed MEG recording without any specific cognitive tasks (ie, resting state). RESULTS: Analysis shows posterior-occipital alpha power to be decreased but fronto-temporal delta/theta power increased in people with PNES compared with HC subjects. Analyses of mean interregional functional connectivity of 54 brain regions, patients with PNES tended to have reduced mean coherence in extra-fronto-temporal regions (ex-FTRs) while increased mean coherence in fronto-temporal regions (FTRs) compared with HC. Furthermore, all 6 patients with PNES had their highest coherence structure within the FTRs. This is in contrast to the HC subjects where only 3 of the 9 subjects had their highest coherence value structure in the FTRs (χ CONCLUSIONS: The above findings are consistent with a disbalance between frontotemporal and posterior brain regions in this population with possible increased excitability in the FTRs. The data support the need for further investigations of the pathophysiology of PNES. The identification of a biomarker for PNES would not only provide for more informed therapeutic approaches, but it could also eliminate the stigma associated with the diagnosis of PNES

Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa

The purpose of the present study was to test the therapeutic efficiency and safety of compacted-DNA nanoparticle-mediated gene delivery into the subretinal space of a juvenile mouse model of retinitis pigmentosa. Nanoparticles containing the mouse opsin promoter and wild-type mouse Rds gene were injected subretinally into mice carrying a haploinsufficiency mutation in the retinal degeneration slow (rds+/−) gene at postnatal day (P)5 and 22. Control mice were either injected with saline, injected with uncompacted naked plasmid DNA carrying the Rds gene, or remained untreated. Rds mRNA levels peaked at postinjection day 2 to 7 (PI-2 to PI-7) for P5 injections, stabilized at levels 2-fold higher than in uninjected controls for both P5 and P22 injections, and remained elevated at the latest time point examined (PI-120). Rod function (measured by electroretinography) showed modest but statistically significant improvement compared with controls after both P5 and P22 injections. Cone function in nanoparticle-injected eyes reached wild-type levels for both ages of injections, indicating full prevention of cone degeneration. Ultrastructural examination at PI-120 revealed significant improvement in outer segment structures in P5 nanoparticle-injected eyes, while P22 injection had a modest structural improvement. There was no evidence of macrophage activation or induction of IL-6 or TNF-α mRNA in P5 or P22 nanoparticle-dosed eyes at either PI-2 or PI-30. Thus, compacted-DNA nanoparticles can efficiently and safely drive gene expression in both mitotic and postmitotic photoreceptors and retard degeneration in this model. These findings, using a clinically relevant treatment paradigm, illustrate the potential for application of nanoparticle-based gene replacement therapy for treatment of human retinal degenerations.—Cai, X., Conley, S. M., Nash, Z., Fliesler, S. J., Cooper, M. J., Naash, M. I. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa