Querschnittslähmung muss heilbar werden – das ambitionierte Ziel der Wings for Life Stiftung

A causal treatment for traumatic Spinal Cord Injury (SCI) is the goal of the charitable Wings for Life Spinal Cord Research Foundation, located in Salzburg. In order realize this ambitioned endeavour, since 2004 Wings for Life competitively funds selected scientific projects aiming at the neurobiological repair of the injured spinal cord.An international Medical/Scientific Board and independent Peer Review Panel composed of more than 200 renowned Scientists and Clinicians (Wings for Life-?Faculty“) specialized on Spinal Cord Injury support the Executive board selecting the most promising projects within a 2 step ?Peer Review“ procedure. To date, Wings for Life funds more than 55 research projects. The projects range from basic science (target finding), applied basic and preclinical research (target validation) to clinical trials.In collaboration with twelve respected, specialized ?non-governmental organisations“ (NGOs), Wings for Life forms the umbrella organisation ICCP (International Campaign for Cures of Spinal Cord Injury) a world-wide network which develops synergies for responsible and effective translational research in spinal cord injury.     

Increased Firearm Injury During the COVID-19 Pandemic: A Hidden Urban Burden

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Role of protein tyrosine phosphatases in the modulation of insulin signaling and their implication in the pathogenesis of obesity-linked insulin resistance

Insulin resistance is a major disorder that links obesity to type 2 diabetes mellitus (T2D). It involves defects in the insulin actions owing to a reduced ability of insulin to trigger key signaling pathways in major metabolic tissues. The pathogenesis of insulin resistance involves several inhibitory molecules that interfere with the tyrosine phosphorylation of the insulin receptor and its downstream effectors. Among those, growing interest has been developed toward the protein tyrosine phosphatases (PTPs), a large family of enzymes that can inactivate crucial signaling effectors in the insulin signaling cascade by dephosphorylating their tyrosine residues. Herein we briefly review the role of several PTPs that have been shown to be implicated in the regulation of insulin action, and then focus on the Src homology 2 (SH2) domain-containing SHP1 and SHP2 enzymes, since recent reports have indicated major roles for these PTPs in the control of insulin action and glucose metabolism. Finally, the therapeutic potential of targeting PTPs for combating insulin resistance and alleviating T2D will be discussed.     

<Emphasis Type="Italic">GSTP1</Emphasis> and <Emphasis Type="Italic">MDR1</Emphasis> Genotypes and Central Nervous System Relapse in Childhood Acute Lymphoblastic Leukemia

The probability of event-free survival of childhood acute lymphoblastic leukemia (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic regimens. One major contribution to this success has been reduction of the rate of central nervous system (CNS) relapses to less than 5%. However, heterogeneity is observed with regard to the incidence of CNS relapse in homogenously treated patient populations. One potential explanation for this heterogeneity is variation in the genetic background of these populations. Glutathione S-transferase P1 and P-glycoprotein are implicated in resistance to a variety of chemotherapeutic agents and have been localized to the blood-brain barrier. In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were observed for patients homozygous for the GSTP1 Val105 allele as well as for patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect was restricted to patients at intermediate or high risk of treatment failure. These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols.     

Young red blood cells; observations about the cytometric and morphologic alterations in the beginning of their life

Summary A recently described separation technique consisting of a combination of counterflow centrifugation and subsequent density (Percoll) scparation was tested for its ability to enrich red cell populations with young cells in comparison to either separation technique alone. The relative age of every fraction was determined by HbAlc measurements, resulting in the lowest HbAlc for the combination method. Conventional reticulocyte counting and floweytometric counting with thiazole orange indicated that in the youngest fractions the combination method showed the highest reticulocyte counts. There was a good correlation between manual and flowcytometric counting results. Radio-iron studies showed a two-fold enrichment with young cells in the fraction with the lowest HbAIc acquired by the combination technique in comparison to the other two methods. Cytometric measurements showed that the fractions with the lowest HbAlc were the ones with the highest MCV and MCH and the lowest MCHC. Besides loss of their RNA-material, young cells already seem to loose water and haemoglobin like older cells, resulting in a decrease of MCV and MCH and in increase in MCHC. It is concluded that combining counterflow centrifugation with subsequent density fractionation results in superior enrichment with young cells in comparison to the results of each method alone.     

Toward the development of peptide nanofilaments and nanoropes as smart materials

Protein design studies using coiled coils have illustrated the potential of engineering simple peptides to self-associate into polymers and networks. Although basic aspects of self-assembly in protein systems have been demonstrated, it remains a major challenge to create materials whose large-scale structures are well determined from design of local protein-protein interactions. Here, we show the design and characterization of a helical peptide, which uses phased hydrophobic interactions to drive assembly into nanofilaments and fibrils ("nanoropes"). Using the hydrophobic effect to drive self-assembly circumvents problems of uncontrolled self-assembly seen in previous approaches that used electrostatics as a mode for self-assembly. The nanostructures designed here are characterized by biophysical methods including analytical ultracentrifugation, dynamic light scattering, and circular dichroism to measure their solution properties, and atomic force microscopy to study their behavior on surfaces. Additionally, the assembly of such structures can be predictably regulated by using various environmental factors, such as pH, salt, other molecular crowding reagents, and specifically designed "capping" peptides. This ability to regulate self-assembly is a critical feature in creating smart peptide biomaterials.     

Der Schlaganfall beim Diabetespatienten

Diabetes and stroke are important clinical conditions from epidemiological and economical points of view. An interdisciplinary approach is always indicated to diagnose and treat these diseases optimally. Diabetes elevates the risk of stroke between two- and four-fold. Diabetic stroke patients need longer in-patient treatment, have a higher mortality rate and recover less well during the rehabilitation process. Approximately 20%-30% of first-ever stroke patients reveal an impaired glucose tolerance or even manifest diabetes. Already in the prediabetic phase, vessel damage can be seen in the form of endothelial dysfunction and early arteriosclerosis. Measurements of microalbuminuria and intima-media thickness of the common carotid artery enable an assessment of the vascular system. Hyperglycemia represents a serious risk during the acute treatment phase, as it diminishes the effect of thrombolysis and worsens the ischemic parenchymal lesion. Specific neurological signs and symptoms complicate the acute phase of stroke treatment, which should always be carried out in a stroke unit. For secondary prevention purposes, risk-adapted platelet inhibition and statins are recommended.     

Racial/ethnic disparities among women receiving intrauterine transfusions for alloimmunization at a single fetal treatment center

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This “IUT cohort” was compared to an “Alloimmunization cohort”: patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p < .0001), and more non-English speakers (18.6% vs. 4.6%, p = .001). Twenty-one percent (9/43) of patients had immigrated to the United States, all of whom had pregnancies or miscarriages in their country of origin. A third of patients had new antibodies identified on serial screens during the current pregnancy. Significantly more women of Latina ethnicity and non-English speakers required IUTs compared to the cohort of women with alloimmunization. Insufficient access to care prior to arriving in the United States and among racial and ethnic minorities in the United States may contribute to these findings. Providers should be cognizant of potential, racial, and ethnic inequalities among women receiving intrauterine transfusions.