Moving past: probing the agency and affect of recordkeeping in individual and community lives in post-conflict Croatia

Reporting on ongoing research, this paper reviews stories, drawn from recent literature as well as gathered through ethnographic research, that people tell about records and recordkeeping during and since the Yugoslav Wars. It focuses on what these stories reveal of the agency and affect of recordkeeping in individual and community lives, particularly in Croatia. The paper concludes with a contemplation of what might be learned from such an approach for the development of recordkeeping infrastructures that can anticipate, avert or alleviate some of the ways in which records and recordkeeping continue to traumatize or target the vulnerable, and frustrate and prevent the human and societal need to "move forward," if not "move past." © 2014 Springer Science+Business Media Dordrecht

Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID). Anxiety and social withdrawal are considered core features of the FXS phenotype, yet there is limited diagnostic evidence of the prevalence of formal anxiety disorders in FXS. This study assessed the prevalence of anxiety disorders in a sample of 58 males and 39 females with FXS (ages 5.0–33.3 years). Participants’ parents completed the Anxiety Disorders Interview Schedule (ADIS-IV), a clinical interview based on DSM-IV criteria, and the Anxiety Depression and Mood Scale (ADAMS), a psychiatric disorders screening instrument normed in ID. We conducted cognitive (IQ) and autism (AUT) assessments and surveyed medication use. Despite a high rate of psychopharmacological treatment, 86.2% of males and 76.9% of females met criteria for an anxiety disorder, with social phobia and specific phobia the most commonly diagnosed. Proband status, gender, and IQ were not significantly related to any anxiety disorders, however significantly higher rates of a few anxiety disorders were found in older age and AUT groups. Significant correlations between ADIS diagnoses and ADAMS scores provided cross-validation of instruments, indicating that the ADIS is suitable for use in FXS. A greater percentage of our sample met criteria for most anxiety disorders than has been reported in other ID groups or the general population. The rate of anxiety compared to general ID suggests that the FMR1 full mutation confers an especially high risk for these disorders, regardless of factors commonly associated with FXS clinical involvement. A thorough clinical assessment and treatment of anxiety should be included in the FXS standard of care

Nef Alleles from All Major HIV-1 Clades Activate Src-Family Kinases and Enhance HIV-1 Replication in an Inhibitor-Sensitive Manner

The HIV-1 accessory factor Nef is essential for high-titer viral replication and AIDS progression. Nef function requires interaction with many host cell proteins, including specific members of the Src kinase family. Here we explored whether Src-family kinase activation is a conserved property of Nef alleles from a wide range of primary HIV-1 isolates and their sensitivity to selective pharmacological inhibitors. Representative Nef proteins from the major HIV-1 subtypes A1, A2, B, C, F1, F2, G, H, J and K strongly activated Hck and Lyn as well as c-Src to a lesser extent, demonstrating for the first time that Src-family kinase activation is a highly conserved property of primary M-group HIV-1 Nef isolates. Recently, we identified 4-amino substituted diphenylfuropyrimidines (DFPs) that selectively inhibit Nef-dependent activation of Src-family kinases as well as HIV replication. To determine whether DFP compounds exhibit broad-spectrum Nef-dependent antiretroviral activity against HIV-1, we first constructed chimeric forms of the HIV-1 strain NL4-3 expressing each of the primary Nef alleles. The infectivity and replication of these Nef chimeras was indistinguishable from that of wild-type virus in two distinct cell lines (U87MG astroglial cells and CEM-T4 lymphoblasts). Importantly, the 4-aminopropanol and 4-aminobutanol derivatives of DFP potently inhibited the replication of all chimeric forms of HIV-1 in both U87MG and CEM-T4 cells in a Nef-dependent manner. The antiretroviral effects of these compounds correlated with inhibition of Nef-dependent activation of endogenous Src-family kinases in the HIV-infected cells. Our results demonstrate that the activation of Hck, Lyn and c-Src by Nef is highly conserved among all major clades of HIV-1 and that selective targeting of this pathway uniformly inhibits HIV-1 replication

A High-Resolution View of Genome-Wide Pneumococcal Transformation

Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae. To characterise the process in detail, the genomes of 124 S. pneumoniae isolates produced through in vitro transformation were sequenced and recombination events detected. Those recombinations importing the selected marker were independent of unselected events elsewhere in the genome, the positions of which were not significantly affected by local sequence similarity between donor and recipient or mismatch repair processes. However, both types of recombinations were sometimes mosaic, with multiple non-contiguous segments originating from the same molecule of donor DNA. The lengths of the unselected events were exponentially distributed with a mean of 2.3 kb, implying that recombinations are stochastically resolved with a fixed per base probability of 4.4×10−4 bp−1. This distribution of recombination sizes, coupled with an observed under representation of large insertions within transferred sequence, suggests transformation has the potential to reduce the size of bacterial genomes, and is unlikely to act as an efficient mechanism for the uptake of accessory genomic loci

Hippocampal state-dependent behavioral reflex to an identical sensory input in rats.

We examined the local field potential of the hippocampus to monitor brain states during a conditional discrimination task, in order to elucidate the relationship between ongoing brain states and a conditioned motor reflex. Five 10-week-old Wistar/ST male rats underwent a serial feature positive conditional discrimination task in eyeblink conditioning using a preceding light stimulus as a conditional cue for reinforced trials. In this task, a 2-s light stimulus signaled that the following 350-ms tone (conditioned stimulus) was reinforced with a co-terminating 100-ms periorbital electrical shock. The interval between the end of conditional cue and the onset of the conditioned stimulus was 4±1 s. The conditioned stimulus was not reinforced when the light was not presented. Animals successfully utilized the light stimulus as a conditional cue to drive differential responses to the identical conditioned stimulus. We found that presentation of the conditional cue elicited hippocampal theta oscillations, which persisted during the interval of conditional cue and the conditioned stimulus. Moreover, expression of the conditioned response to the tone (conditioned stimulus) was correlated with the appearance of theta oscillations immediately before the conditioned stimulus. These data support hippocampal involvement in the network underlying a conditional discrimination task in eyeblink conditioning. They also suggest that the preceding hippocampal activity can determine information processing of the tone stimulus in the cerebellum and its associated circuits

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

BACKGROUND: Individuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover. METHODS: Fifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed. RESULTS: Early abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal. CONCLUSION: The results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient

Network-Based Prediction and Analysis of HIV Dependency Factors

HIV Dependency Factors (HDFs) are a class of human proteins that are essential for HIV replication, but are not lethal to the host cell when silenced. Three previous genome-wide RNAi experiments identified HDF sets with little overlap. We combine data from these three studies with a human protein interaction network to predict new HDFs, using an intuitive algorithm called SinkSource and four other algorithms published in the literature. Our algorithm achieves high precision and recall upon cross validation, as do the other methods. A number of HDFs that we predict are known to interact with HIV proteins. They belong to multiple protein complexes and biological processes that are known to be manipulated by HIV. We also demonstrate that many predicted HDF genes show significantly different programs of expression in early response to SIV infection in two non-human primate species that differ in AIDS progression. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of AIDS development. More generally, if multiple genome-wide gene-level studies have been performed at independent labs to study the same biological system or phenomenon, our methodology is applicable to interpret these studies simultaneously in the context of molecular interaction networks and to ask if they reinforce or contradict each other