Notes from the Balkans Green, Sarah F
2016, 2005., 20160926, 2005, 2005-01-01, 20050101, Letnik:
20
eBook
Maps and borders notwithstanding, some places are best described as "gaps"--places with repeatedly contested boundaries that are wedged in between other places that have clear boundaries. This book ...explores an iconic example of this in the contemporary Western imagination: the Balkans. Drawing on richly detailed ethnographic research around the Greek-Albanian border, Sarah Green focuses her groundbreaking analysis on the ambiguities of never quite resolving where or what places are. One consequence for some Greek peoples in this border area is a seeming lack of distinction--but in a distinctly "Balkan" way. In gaps (which are never empty), marginality is, in contrast with conventional understandings, not a matter of difference and separation--it is a lack thereof.
Notes from the Balkans represents the first ethnographic approach to exploring "the Balkans" as an ideological concept. Green argues that, rather than representing a tension between "West" and "East," the Balkans makes such oppositions ambiguous. This kind of marginality means that such places and peoples can hardly engage with "multiculturalism." Moreover, the region's ambiguity threatens clear, modernist distinctions. The violence so closely associated with the region can therefore be seen as part of continual attempts to resolve the ambiguities by imposing fixed separations. And every time this fails, the region is once again defined as a place that will continually proliferate such dangerous ambiguity, and could spread it somewhere else.
The XRN family of 5′→3′ exoribonucleases is critical for ensuring the fidelity of cellular RNA turnover in eukaryotes. Highly conserved across species, the family is typically represented by one ...cytoplasmic enzyme (XRN1/PACMAN or XRN4) and one or more nuclear enzymes (XRN2/RAT1 and XRN3). Cytoplasmic and/or nuclear XRNs have proven to be essential in all organisms tested, and deficiencies can have severe developmental phenotypes, demonstrating that XRNs are indispensable in fungi, plants and animals. XRNs degrade diverse RNA substrates during general RNA decay and function in specialized processes integral to RNA metabolism, such as nonsense-mediated decay (NMD), gene silencing, rRNA maturation, and transcription termination. Here, we review current knowledge of XRNs, highlighting recent work of high impact and future potential. One example is the breakthrough in our understanding of how XRN1 processively degrades 5′ monophosphorylated RNA, revealed by its crystal structure and mutational analysis. The expanding knowledge of XRN substrates and interacting partners is outlined and the functions of XRNs are interpreted at the organismal level using available mutant phenotypes. Finally, three case studies are discussed in more detail to underscore a few of the most exciting areas of research on XRN function: XRN4 involvement in small RNA-associated processes in plants, the roles of XRN1/PACMAN in Drosophila development, and the function of human XRN2 in nuclear transcriptional quality control. This article is part of a Special Issue entitled: RNA Decay mechanisms.
•XRNs degrade diverse RNAs in the nucleus and cytoplasm of eukaryotes.•Crystal structure and interaction studies enhance mechanistic understanding.•Mutant phenotypes illustrate roles of XRNs in development, stress and more.•Cases highlight exciting Drosophila XRN1, human XRN2, and plant XRN4 functions.
Abstract
BACKGROUND
Targeting of the motor thalamus for the treatment of tremor has traditionally been achieved by a combination of anatomical atlases and neuroimaging, intraoperative clinical ...assessment, and physiological recordings.
OBJECTIVE
To evaluate whether thalamic nuclei targeted in tremor surgery could be identified by virtue of their differing connections with noninvasive neuroimaging, thereby providing an extra factor to aid successful targeting.
METHODS
Diffusion tensor tractography was performed in 17 healthy control subjects using diffusion data acquired at 1.5-T magnetic resonance imaging (60 directions, b value = 1000 s/mm2, 2 × 2 × 2-mm3 voxels). The ventralis intermedius (Vim) and ventralis oralis posterior (Vop) nuclei were identified by a stereotactic neurosurgeon, and these sites were used as seeds for probabilistic tractography. The expected cortical connections of these nuclei, namely the primary motor cortex (M1) and contralateral cerebellum for the Vim and M1, the supplementary motor area, and dorsolateral prefrontal cortex for the Vop, were determined a priori from the literature.
RESULTS
Tractogram signal intensity was highest in the dorsolateral prefrontal cortex and supplementary motor area after Vop seeding (P > .001, Wilcoxon signed-rank tests). High intensity was seen in M1 after seeding of both nuclei but was greater with Vim seeding (P > .001). Contralateral cerebellar signal was highest with Vim seeding (P > .001).
CONCLUSION
Probabilistic tractography can depict differences in connectivity between intimate nuclei within the motor thalamus. These connections are consistent with published anatomical studies; therefore, tractography may provide an important adjunct in future targeting in tremor surgery.
Open electronic cigarette (e-cigarette) systems are customizable by consumers and often allow for potential "unorthodox" use of the product; that is, use not as intended by the manufacturer. Little ...is known about the types and prevalence of unorthodox uses and how these practices are transmitted via popular social media.
Monthly searches of YouTube were conducted from June through November 2016 using the following search terms: "e-cigarettes," "vaping," and "e-juice." After collecting static and dynamic data on the 150 videos identified, two coders independently coded videos for general information, unorthodox use behaviors, health claims, and production quality and characteristics for orthodox and unorthodox use. Intercoder reliability was high (Cohen's κ 0.81, p < .001).
One hundred fifty videos were included in the study with a total of 115 551 563 views. We identified nine categories of unorthodox uses of e-cigarettes. Unorthodox use was three times as prevalent as orthodox use. Seventy-seven percent of the unorthodox use videos included recreational e-cigarette use, 57% included modification of mechanical parts and components, and 44.6% included unorthodox substance application (dripping). There were more than twice as many social media links in videos depicting unorthodox compared to orthodox use, but the level of engagement was lower for unorthodox use.
E-cigarette unorthodox use on YouTube is more prevalent than orthodox use, suggesting the need to further investigate the prevalence of unorthodox use among e-cigarette users and the influence of social media on consumer uptake of unorthodox and orthodox uses of e-cigarettes.
The US Food and Drug Administration has regulatory authority over e-cigarettes, parts and components. Many e-cigarettes currently marketed are open systems. Closed systems may allow less manipulation and may influence the safety of these products. This study provides valuable information on ways that open system e-cigarettes are used and it can inform safety tests that can be conducted by the US Food and Drug Administration to determine whether or not these products should remain on the market. In addition, our definitions of unorthodox use can be incorporated into the Population Assessment of Tobacco on Health Study to better understand the prevalence of these behaviors.
De novo mutations in
have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and ...neonatal hypotonia.
To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations.
Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of
-derived Pur-alpha homologues. Finally, we explored genotype-phenotype correlations by analysis of both recurrent mutations as well as mutation classes.
We report mutations in
(purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes.
We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.
Deep brain stimulation (DBS) is a remarkably effective clinical tool, used primarily for movement disorders. DBS relies on precise targeting of specific brain regions to rebalance the oscillatory ...behaviour of whole-brain neural networks. Traditionally, DBS targeting has been based upon animal models (such as MPTP for Parkinson's disease) but has also been the result of serendipity during human lesional neurosurgery. There are, however, no good animal models of psychiatric disorders such as depression and schizophrenia, and progress in this area has been slow. In this paper, we use advanced tractography combined with whole-brain anatomical parcellation to provide a rational foundation for identifying the connectivity 'fingerprint' of existing, successful DBS targets. This knowledge can then be used pre-surgically and even potentially for the discovery of novel targets. First, using data from our recent case series of cingulate DBS for patients with treatment-resistant chronic pain, we demonstrate how to identify the structural 'fingerprints' of existing successful and unsuccessful DBS targets in terms of their connectivity to other brain regions, as defined by the whole-brain anatomical parcellation. Second, we use a number of different strategies to identify the successful fingerprints of structural connectivity across four patients with successful outcomes compared with two patients with unsuccessful outcomes. This fingerprinting method can potentially be used pre-surgically to account for a patient's individual connectivity and identify the best DBS target. Ultimately, our novel fingerprinting method could be combined with advanced whole-brain computational modelling of the spontaneous dynamics arising from the structural changes in disease, to provide new insights and potentially new targets for hitherto impenetrable neuropsychiatric disorders.
Bovine respiratory disease (BRD) remains the leading disease within the U.S. beef cattle industry. Marketing decisions made prior to backgrounding may shift BRD incidence into a different phase of ...production, and the importance of host gene expression on BRD incidence as it relates to marketing strategy is poorly understood. Our objective was to compare the influence of marketing on host transcriptomes measured on arrival at a backgrounding facility on the subsequent probability of being treated for BRD during a 45-day backgrounding phase. This study, through RNA-Seq analysis of blood samples collected on arrival, evaluated gene expression differences between cattle which experienced a commercial auction setting (AUCTION) versus cattle directly shipped to backgrounding from the cow-calf phase (DIRECT); further analyses were conducted to determine differentially expressed genes (DEGs) between cattle which remained clinically healthy during backgrounding (HEALTHY) versus those that required treatment for clinical BRD within 45 days of arrival (BRD). A profound difference in DEGs (n = 2961) was identified between AUCTION cattle compared to DIRECT cattle, regardless of BRD development; these DEGs encoded for proteins involved in antiviral defense (increased in AUCTION), cell growth regulation (decreased in AUCTION), and inflammatory mediation (decreased in AUCTION). Nine and four DEGs were identified between BRD and HEALTHY cohorts in the AUCTION and DIRECT groups, respectively; DEGs between disease cohorts in the AUCTION group encoded for proteins involved in collagen synthesis and platelet aggregation (increased in HEALTHY). Our work demonstrates the clear influence marketing has on host expression and identified genes and mechanisms which may predict BRD risk.
For almost one hundred years, the exact role of human brain structures controlling the cardiorespiratory response to exercise
(âcentral commandâ) has been sought. Animal experiments and ...functional imaging studies have provided clues, but the underlying
electrophysiological activity of proposed relevant neural sites in humans has never been measured. In this study, local field
potentials were directly recorded in a number of âdeepâ brain nuclei during an exercise task designed to dissociate the exercise
from peripheral feedback mechanisms. Several patient groups had electrodes implanted sterotaxically for the treatment of movement
disorder or chronic pain. Fast Fourier transform analysis was applied to the neurograms to identify the power of fundamental
spectral frequencies. Anticipation of exercise resulted in increases in heart rate, blood pressure and ventilation. The greatest
neural changes were found in the periaqueductal grey area (PAG) where anticipation of exercise was accompanied by an increase
of 43% in the power of the 12â25 Hz frequency band ( P
= 0.007). Exercise increased the activity by 87% compared to rest ( P
= 0.006). Changes were also seen in the 60â90 Hz band when anticipation or exercise increased power by 32% ( P
= 0.006) and 109% ( P < 0.001), respectively. In the subthalamic nucleus there was a reduction in the power of the beta frequency during both anticipation
(7.6 ± 0.68%
P
= 0.001) and exercise (17.3 ± 0.96%
P < 0.001), whereas an increase was seen with exercise only at higher frequencies (93 ± 1.8%
P
= 0.007). No significant changes were seen in the globus pallidus during anticipation of exercise. We provide direct
electrophysiological evidence highlighting the PAG as an important subcortical area in the neural circuitry of the cardiorespiratory
response to exercise, since stimulation of this structure is known to alter blood pressure in awake humans.
•A method was developed for analysis of an acetaminophen protein adduct biomarker.•The method quantifies protein-derived acetaminophen-cysteine in human serum.•The assay was validated on two ...different HPLC-ESI-MS/MS platforms.•The assay was applied to clinical and mouse-model study samples.
The aims of this study were to develop, validate, and apply a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method for quantification of protein-derived 3-(cystein-S-yl)-acetaminophen (APAP-Cys) in human serum. Formation of acetaminophen (APAP) protein adducts is thought to be a critical, early event in the development of APAP-induced hepatotoxicity, and quantification of these protein adducts in human serum represents a valuable tool for assessment of APAP exposure, metabolism, and toxicity. In the reported procedure, serum samples were first dialyzed or passed through gel filtration columns to remove APAP-Cys not covalently bound to proteins. Serum eluates were then subjected to enzymatic protease digestion to liberate protein-bound APAP-Cys. Norbuprenorphine-D3 was utilized as an internal standard (IS). APAP-Cys and IS were recovered from digested serum by protein precipitation with acetonitrile, and sample extracts were analyzed by HPLC-ESI-MS/MS. The method was validated by assessment of intra- and inter-assay accuracy and imprecision on two different analytical instrument platforms. APAP-Cys could be accurately quantified from 0.010 to 10μM, and intra- and inter-assay imprecision were <15% on both analytical instruments. APAP-Cys was stable in human serum for three freeze-thaw cycles and for 24h at ambient temperature. Extracted samples were stable when stored in refrigerated autosamplers for the typical duration of analysis or when stored at −20°C for six days. Results from process efficiency and matrix effect experiments indicated adequate recovery from human serum and insignificant ion suppression or enhancement. The utility and sensitivity of the reported procedure were illustrated by analysis of clinical samples collected from subjects taking chronic, therapeutic doses of APAP. Applicability to other biological matrices was also demonstrated by measurement of protein-derived APAP-Cys in plasma collected from APAP-treated mice, a common animal model of APAP-induced hepatotoxicity.
The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment‐resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some ...progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain’s default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery.
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