Dissecting the brain`s fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders

Effective defense against natural threats in the environment is essential for the survival of individual animals. Thus, instinctive behavioral responses accompanied by fear have evolved to protect individuals from predators and from opponents of the same species (dominant conspecifics). While it has been suggested that all perceived environmental threats trigger the same set of innately determined defensive responses, we tested the alternate hypothesis that different stimuli may evoke differentiable behaviors supported by distinct neural circuitry. The results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments indicate that the hypothalamus is necessary for full expression of defensive behavioral responses in a subordinate conspecific, that lesions of the dorsal premammillary nucleus drastically reduce behavioral measures of fear in these animals, and that essentially separate hypothalamic circuitry supports defensive responses to a predator or a dominant conspecific. It is now clear that differentiable neural circuitry underlies defensive responses to fear conditioning associated with painful stimuli, predators, and dominant conspecifics and that the hypothalamus is an essential component of the circuitry for the latter two stimuli.

Att leva med diagnosen Abdominellt Aorta Aneurysm : -en litteraturstudie om upplevelser kring sjukdom och omvårdnad ur ett patientperspektiv

Bakgrund: Över 150 000 människor i Sverige behandlas årligen för hjärt- och kärlsjukdom. En vanlig form är ateroskleros, åderförkalkning. Av alla de som idag avlider på grund av annan orsak än naturligt åldrande, gör de flesta det av komplikationer till aterosklerossjukdom. En av dessa komplikationer är aortaanerysm, mera känt som ”pulsåderbråck”. Det vanligast förekommande är abdominellt aortaanerysm, bukaortaaneurysm. Syfte: Syftet med denna studie var att belysa livssituationer, livskvalitet och omvårdnadsbehov hos patienter med diagnosen AAA samt att visa på omvårdnadsåtgärder som främjar hälsa hos patienter med denna diagnos. Metod: En litteraturgranskning gjordes i databaserna PubMed, Chinal och Psychinfo samt Högskolan Dalarnas sökmotor Elin. Artiklarna valdes ut efter relevans till syftet. Dess kvalitet värderades med hjälp av granskningsmallar. Fyra kvalitativa och 16 kvantitativa ansatser ingick i studien. Resultat: Det framkom att HRQoL hos patienter som fick diagnosen AAA försämrades signifikant perioperativt. Oro och rädsla samt känslor av overklighet, nära döden upplevelser och existentiella frågor var vanligt perioperativt. Ingen påvisbar skillnad före och efter screening i HRQoL eller upplevd hälsa iakttogs. Mer information kring exempelvis sexualitet perioperativt kunde lindra oro och rädsla. Diskussion: Omvårdnaden är otillräcklig vid diagnostillfället samt postoperativt. Screening har positiv inverkan på patienternas generella hälsa. Konklusion: Studien visade på ökat behov av omvårdnad i samband med att diagnosen ställts samt efter utskrivning postoperativt.

Dissecting computer fraud : from definitional issues to a taxonomy

Computer frauds, while less dramatic than crimes of violence, can inflict significant damage at community, organizational or individual level. In order to properly quantify and mitigate the risk, computer frauds needs to be well understood. In this paper, in a conceptual-analytical research approach, we propose a dissection of computer fraud. First, we look into the elements of an offense, the act of fraud in general, than explain what is and what is not computer fraud. Next, from a prevention perspective, we propose a taxonomy of computer fraud with respect to perpetration platform, and to perpetration method. We believe that our contributions extend the existing knowledge of the phenomenon, and can assist those fighting computer fraud to better understand it and to design means of preventing and reporting it.

Dissecting obesogenic behaviours: the development and application of a test battery for targeting prescription for weight loss

There are limited practical tools to help clinicians or public health workers manage obesity in their patients. We have previously developed a scanning technique for diagnosing environments leading to obesity (Analysis Grid for Environments/Elements Leading to Obesity). Here we describe the development of a tool for identifying behaviours in an individual most likely to lead to obesity. A questionnaire battery of five tests called the DAB-Q (Diet, Activity and Behaviour Questionnaire) was developed, piloted and internally validated with overweight women from a commercial weight loss programme. Outcome from the tests, which are available free on the Internet, provides clinicians with a simple, effective and time-saving tool for ranking foods, drinks and activities likely to be most effectively targeted for weight loss in an individual. This is based on total scores derived from measures of frequency, potential for change and potency of each item as a potential contributor to overweight.

Dissecting isoform selectivity of P13K inhibitors: the role of non-conserved residues in the catalytic pocket

The last few years have seen the identification of numerous small molecules that selectively inhibit specific class I isoforms of PI3K (phosphoinositide 3-kinase), yet little has been revealed about the molecular basis for the observed selectivities. Using site-directed mutagenesis, we have investigated one of the areas postulated as being critical to the observed selectivity. The residues Thr⁸⁸⁶ and Lys⁸⁹⁰ of the PI3Kγ isoform project towards the ATP-binding pocket at the entrance to the catalytic site, but are not conserved. We have made reciprocal mutations between those residues in the β isoform (Glu⁸⁵⁸ and Asp⁸⁶²) and those in the α isoform (His⁸⁵⁵ and Gln⁸⁵⁹) and evaluated the potency of a range of reported PI3K inhibitors. The results show that the potencies of β-selective inhibitors TGX221 and TGX286 are unaffected by this change. In contrast, close analogues of these compounds, particularly the α-isoform-selective compound (III), are markedly influenced by the point mutations. The collected data suggests two distinct binding poses for these inhibitor classes, one of which is associated with potent PI3Kβ activity and is not associated with the mutated residues, and a second that, in accord with earlier hypotheses, does involve this pair of non-conserved amino acids at the catalytic site entrance and contributes to the α-isoform-selectivity of the compounds studied.

Dissecting the role of SOCS proteins using zebrafish

Suppressors of cytokine signalling (SOCS) proteins are negative regulators of the JAK-STAT pathway which is perturbed in certain disease states including cancers and inflammatory diseases. This thesis ascertained the suitability of zebrafish as an alternative animal model to study the SOCS proteins which established new and additional roles during development.

In vitro strain measurements in cerebral aneurysm models for cyber-physical diagnosis

Background: The development of new diagnostic technologies for cerebrovascular diseases requires an understanding of the mechanism behind the growth and rupture of cerebral aneurysms. To provide a comprehensive diagnosis and prognosis of this disease, it is desirable to evaluate wall shear stress, pressure, deformation and strain in the aneurysm region, based on information provided by medical imaging technologies. Methods: In this research, we propose a new cyber-physical system composed of in vitro dynamic strain experimental measurements and computational fluid dynamics (CFD) simulation for the diagnosis of cerebral aneurysms. A CFD simulation and a scaled-up membranous silicone model of a cerebral aneurysm were completed, based on patient-specific data recorded in August 2008. In vitro blood flow simulation was realized with the use of a specialized pump. A vision system was also developed to measure the strain at different regions on the model by way of pulsating blood flow circulating inside the model. Results: Experimental results show that distance and area strain maxima were larger near the aneurysm neck (0.042 and 0.052), followed by the aneurysm dome (0.023 and 0.04) and finally the main blood vessel section (0.01 and 0.014). These results were complemented by a CFD simulation for the addition of wall shear stress, oscillatory shear index and aneurysm formation index. Diagnosis results using imaging obtained in August 2008 are consistent with the monitored aneurysm growth in 2011. Conclusion: The presented study demonstrates a new experimental platform for measuring dynamic strain within cerebral aneurysms. This platform is also complemented by a CFD simulation for advanced diagnosis and prediction of the growth tendency of an aneurysm in endovascular surgery.

A global approach to dissecting lipid-induced impairment of liver gluconeogenesis

This thesis identified: 1) novel aspects of cholesterol metabolism, 2) a novel signalling lipid in the phosphatidylinositol class, and 3) a gene involved in regulating lipid breakdown, as being regulated in the reversal of a fatty acid induced diabetic liver. The identification of these targets may allow for future development of targeted therapies against type 2 diabetes with a specific focus on the liver.

In vitro simulator with numerical stress analysis for evaluation of stent-assisted coiling embolization in cerebral aneurysm treatments

There are several complications associated with Stent-assisted Coil Embolization (SACE) in cerebral aneurysm treatments, due to damaging operations by surgeons and undesirable mechanical properties of stents. Therefore, it is necessary to develop an in vitro simulator that provides both training and research for evaluating the mechanical properties of stents.

Dissecting the role of the ETV6 transcriptional regulator in development and disease

This study studied the ETV6 gene using zebrafish as a model. The work demonstrated that ETV6 was important for the development of both white and red blood cells. It also characterized the pathogenic effects of mutant forms of ETV6 found in various leukemias and other blood disorders.