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- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
- 2010
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Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have previously demonstrated that in young rats (12-20-day-old) a sustained long-term potentiation (LTP) can still be induced under conditions of protein synthesis inhibition. It was therefore suggested that sufficient and necessary proteins were already available at the induction time to accomplish LTP maintenance for several hours. Against this background, we have questioned whether hippocampal slices subjected to certain insult conditions might be more sensitive to protein synthesis inhibitors. High K+ concentration has previously been reported to cause an amnesic effect in vivo as well as increasing protein turnover in vitro. We have here employed a K+ insult model under conditions when protein synthesis was inhibited. Recordings were obtained from hippocampal slices for up to 9 h, with or without a cocktail of protein synthesis inhibitors, containing cycloheximide (60 µM) and anisomycin (25 µM). High potassium (50 mM) was transiently applied (5-15 min) shortly after inducing LTP in one of two separate pathways stimulated alternatively. Additionally, an NMDA-receptor antagonist AP5 was supplied after LTP induction to minimize effects related to depolarization-induced glutamate release. Following elimination of all responses for about 30 min, both test and control responses partly recovered. The degree of remaining LTP, defined as test/control ratio, was reduced in both groups of slices (NMDA-independent depotentiation) but was significantly smaller in the drug-treated ones. We are also running an insult model based on oxidative stress, applying hydrogen peroxide (4-5 mM) before or after LTP induction; however, the results are still insufficient for a final conclusion. The potency of cycloheximide, anisomycin or cocktail of the drugs was verified by measurement of incorporation of [3H]-leucine into trichloracetic acid (TCA) precipitable macromolecules. Cycloheximide, anisomycin or cocktail, at concentrations used here caused 95%, 97% and 95% blocking effect, respectively. Our data confirm the idea that sufficient and necessary constitutive proteins are available in the young hippocampus to maintain LTP under conditions of protein synthesis inhibition. They also reveal that LTP in slices subjected to certain insult conditions early after the induction is sensitive to protein synthesis inhibition, probably due to increase in constitutive proteins turnover.
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| 2. |
- Trägårdh, Karin, et al.
(författare)
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Risk Profiles of Female Perpetrators of Severe Violence
- 2019
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Ingår i: 13th Nordic Symposium on Forensic Psychiatry. August 20-22, Gothenburg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Female offenders without a severe mental disorder show more criminogenic factors than those with. Both groups are characterized by mental health problems. We need to further characterize female offenders. Background Offenders of lethal/severe violence are in a majority of cases male, about 90% (Falk et al., 2014), and research has to a considerable extent focused on male violent offenders. Although less is known about female violent offenders than male offenders, previous research has indicated significant differences between male and female offenders of lethal/severe violence (Trägårdh et al., 2016; Yourstone et al., 2008). Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation (RPU/FPI), these documents contains important information about this group. Purpose The aim of this ongoing study is to characterize female perpetrators of severe violent crimes, and to compare female perpetrators sentenced to forensic psychiatric compulsory care with those sentenced to correctional treatment. Method This is an exploratory and descriptive study with a cross-sectional design. All forensic evaluations (FPI) made in Sweden between 2000-2014 (from The National Board of Forensic Medicine/RMV), and the subsequent court verdicts, in cases where women had used lethal/severe violence (n≈180) where used as the basis for data collection in this study. The present preliminary analyses (2-tests and ANOVA) contains approx. 26% (n=47) of the total group. Group differences were investigated regarding: Mental health (FPI) Risk factors (HCR-20 and PCL-R) Victim relation (FPI) Criminal behavior (FPI) Results Female offenders with and without a Severe mental disorder (SMD) seems to differ in some respects. For female offenders with a SMD, the crime was more likely to have been conducted in a less criminal context (see Table). For female offenders without a SMD, the following characteristics were more frequently present: Victim gender – male Substance abuse + Under the influence of substance (offender and victim) Previous violence between victim and offender Previous registered criminality Also, several common features between the SMD and non-SMD group of female offenders were found. The majority of all female offenders had: Previous psychiatric contact and diagnoses Previously attempted suicide No previously registered criminality Conclusions Preliminary results of the female perpetrators who had underwent a FPI seems to identify both substantial differences and similarities between those with versus without a SMD, where those without show more criminogenic factors. Both groups were also characterized by a high amount of mental illness. Also, these results supports previous research that female and male offenders of severe violence differ in important ways. Since a majority of female perpetrators of lethal violence undergo a forensic psychiatric investigation, these results should be generalizable to this group as a whole in Sweden. Based on these results, a great need to further characterize female offenders of severe/lethal violence remain.
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| 4. |
- Munthe, Christian, 1962
(författare)
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The Return of Lombroso? Ethical and Philosophical Aspects of (Visions of) Forensic Screening
- 2013
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Ingår i: 33rd International Congress of Law and Mental Health, Amsterdam, July 14-19, 2013.
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Konferensbidrag (refereegranskat)abstract
- Italian nineteenth century criminologist Cesare Lombroso is notorious for his seminal ideas about criminality and anti-social behaviour resulting from physiological anomalies that should be detected by society and used for forensic preventive purposes. After an extended period of disrepute following World War II, similar ideas have been resurrected in psychiatry, genetics, neurology and criminology in the past decade or two. In particular, there is a growing focus on early detection and application of preventive measures. This development actualizes a complex web of ethics and policy issues having to do with the well-known fact that screening and prevention in the health area are far from ethically clear-cut activities and actualize vivid prospects of doing extensive harm to individuals as well as society. Also, taken to its extreme, it actualizes the idea of using prenatal or preimplantation testing to preselect against children with a predisposition for criminal or antisocial behaviour. In the forensic case, such screening-prevention strategies will connect further to a complicated issue about the proper use of risk-assessment models for societal decision-making for precautionary purposes. Based on former work in all of these areas, this presentation will outline and analyze the basic issue of the defensibility of activities of this sort, with the perspective of forestalling unintentional harm to individuals and society.
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| 7. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Pharmacological characteristics of protein synthesis inhibitors by radioactive leucine incorporation in rat hippocampal slices: experimental evidence and pre-clinical implications
- 2011
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Ingår i: The 23rd Biennial Meeting of the International Society for Neurochemistry (ISN), August 28-September 1 2011, Athens, Greece.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Protein synthesis inhibitors (PSIs) constitute a major tool to validate the hypothesis of protein synthesis-dependent phase of synaptic plasticity and memory consolidation. However, several reports have showed inconsistent findings about the effect of these drugs on behavioral learning and synaptic plasticity. Testing the potencies of these drugs is hence crucial for validating such negative findings and in planning future studies. It is also necessary to examine the dose dependence, onset dynamics and reversibility, and possible effects on basal proteins. Here we used the labeled leucine as marker for the newly synthesized proteins. The fraction of leucine incorporation, following 50 min of pre-incubation, was compared between two groups of slices: a PSI-treated and a control group. Both anisomycin and cycloheximide revealed a dose-dependent but time-independent manner of inhibition reaching over 92% at concentrations well below those used in previous experiments which revealed effects on synaptic plasticity and learning. Surprisingly, washout of a “reversible” inhibitor, anisomycin was not followed by rapid reversibility of the action of the drug, the case that differs with cycloheximide. Interestingly, emetine revealed a time-dependent inhibition of protein synthesis, where levels above 80% needed drug pre-incubation for as long as 90 min. Since the duration of labeling relates to the half-life of the proteins, short-time labeling as used in this study will result in radioactivity incorporation into short-lived proteins and proteins that are synthesized in large quantities. We therefore studied the availability of newly synthesized proteins at 8-10 h following leucine incorporation. The results revealed virtually the same protein content as in slices retrieved for analysis immediately following the labeling period, indicating that the main pool of the newly synthesized proteins is of intracellular long-lived pool. This likely reflects a stable metabolic state of our prepared slices. These findings challenge current idea on the role of de novo protein synthesis in synaptic plasticity as well as brain changes underlying several neurological and psychiatric disorders.
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| 8. |
- Krona, Cecilia, et al.
(författare)
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GLIOBLASTOMA GROWTH IS SHAPED BY INVASION ROUTE-SPECIFIC FUNCTIONAL SIGNATURES
- 2023
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Ingår i: Neuro-Oncology. - 1522-8517. ; 25:Supplement: 5, MODL-16
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- One of the defining features of glioblastomas (GBMs) is the capacity for invasive growth along multiple anatomical pathways in the brain. GBM is well-studied on a genetic and molecular level, but clinically relevant and experimentally tractable models of invasive growth are largely lacking. Here, we report an integrated study of patient-matched information, genomic- and molecular profiles with growth in mouse brains to expose treatments and biomarkers associated with glioblastoma invasion and recurrence. In total, 64 patient-derived cell lines (PDCLs) were injected into the striatum of n ≥ 4 mice each. The 45 tumor-forming PDCLs were each scored for 10 distinct growth characteristics (n = 182 mice). The repertoire of phenotypes was highly divergent, and our material included clear cases of perivascular route invasion, white matter route invasion, perineuronal satellitosis, and gliosarcoma. We explored if cellular pathways, monitored by RNA-sequencing, could account for these differences. GSEA highlighted a positive enrichment for highly proliferative proneural tumors characterized by Notch activation, neuronal signaling, and epigenetic gene regulatory programs in the tumor-initiating lines. Transcriptional signatures were also strongly predictive of route-specific invasion. Diffuse invasion was predominantly seen in classical-subtype PDCLs with astrocytic or outer radial glia-like signatures. Proneural PDCLs, in turn, grew as solid tumors with an invasive peripheral region around vasculature, and mesenchymal tumors were more demarcated. To explore the therapeutic implications of our findings, we used our data-driven method (TargetTranslator, Nat Comm 2020) to predict the drug vulnerabilities of different types of invasive glioblastoma. Defined GBM tumors with perivascular invasion are characterized by increased IGFR1, MAPK/ERK, PI3K/AKT/mTOR, and JAK2 signaling. Diffusively growing GBM tumors, on the other hand, depend more on Wnt/β-catenin signaling, neuronal signaling, and active inflammatory response. Using a sphere invasion assay, we confirm that targeting both PI3K- and Wnt signaling selectively reduces glioblastoma invasion, highlighting their therapeutic potential.
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| 9. |
- Lendaro, Eva, 1989, et al.
(författare)
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Differential Activation of Biceps Brachii Muscle Compartments for Human-Machine Interfacing
- 2018
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Ingår i: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS. - 1557-170X. ; 2018-July, s. 4705-4709
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Konferensbidrag (refereegranskat)abstract
- A central challenge for myoelectric limb prostheses resides in the fact that, as the level of amputation becomes more proximal, the number of functions to be replaced increases, while the number of muscles available to collect input signals for control decreases. Differential activation of compartments from a single muscle could provide additional control sites. However, such feat is not naturally under voluntary control. In this study, we investigated the feasibility of learning to differentially activate the two heads of the bicep brachii muscle (BBM), by using biofeedback via high-density surface electromyography (HD-sEMG). Using a one degree of freedom Fitts' law test, we observed that eight subjects could learn to control the center of gravity of BBM's myoelectric activity. In addition, we examined the activations patterns of BBM that allow for the decoding of distal hand movements. These patterns were found highly individual, but different enough to allow for decoding of motor volition of distal joints. These findings represent promising venues to increase the functionality of myoelectrically controlled upper limb prostheses.
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