Amyloid formation of bovine insulin is retarded in moderately acidic pH and by addition of short-chain alcohols

Protein aggregation and amyloid formation are associated with multiple human diseases, but are also a problem in protein production. Understanding how aggregation can be modulated is therefore of importance in both medical and industrial contexts. We have used bovine insulin as a model protein to explore how amyloid formation is affected by buffer pH and by the addition of short-chain alcohols. We find that bovine insulin forms amyloid fibrils, albeit with different rates and resulting fibril morphologies, across a wide pH range (2-7). At pH 4.0, bovine insulin displayed relatively low aggregation propensity in combination with high solubility; this condition was therefore chosen as basis for further exploration of how bovine insulin\u27s native state can be stabilized in the presence of short-chain alcohols that are relevant because of their common use as eluents in industrial-scale chromatography purification. We found that ethanol and isopropanol are efficient modulators of bovine insulin aggregation, providing a three to four times retardation of the aggregation kinetics at 30-35% (vol/vol) concentration; we attribute this to the formation of oligomers, which we detected by AFM. We discuss this effect in terms of reduced solvent polarity and show, by circular dichroism recordings, that a concomitant change in alpha-helical packing of the insulin monomer occurs in ethanol. Our results extend current knowledge of how insulin aggregates, and may, although bovine insulin serves as a simplistic model, provide insights into how buffers and additives can be fine-tuned in industrial production of proteins in general and pharmaceutical insulin in particular

The role of intrinsic pathway in apoptosis activation and progression in Peyronie’s disease

Peyronie’s disease (PD) is a connective tissue disorder where formation of fibrous plaques in tunica albuginea (TA) and erectile tissue can result in penile deformity, pain, and erectile dysfunction. Fibrosis, its major pathological manifestation, arises from fibroblast proliferation and accumulation of extracellular matrix; PD progresses with formation of plaques or even ectopic calcification having the appearance of scar tissue, which prevent TA expansion during erections. The mechanisms underpinning PD are unclear, and relatively little is known about the disease itself. To date corrective surgery is the sole effective treatment. A greater understanding of PD pathophysiology at the molecular level has the potential to help develop novel medical therapeutic approaches. The aim of this study was to investigate the activation of the apoptotic intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD and control patients were assessed for the expression of bax, bcl-2, caspase 9 and 3 using immunohistochemistry, and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplasic bone tissue, in fibroblasts and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplasic bone tissue. Apoptotic cell death occurs in stabilized PD plaques and is partly induced by the intrinsic mitochondrial pathway. The present findings can have clinical implications and may help devise improved treatment strategies. A therapeutic approach aimed at enhancing apoptosis-inducing molecules would at least help delay the progression of PD. Identification of target molecules for gene construct or biological or chemical reagent delivery to target sites could contribute to induce PD plaque stabilization

Mobility as a contradictory resource: Peripatetic Qur’anic students in Kano, Nigeria

Mobility is a powerful resource young people can draw on to improve their lives, but it can also entail risks. This paper explores how mobility becomes a contradictory resource for peripatetic Qur'anic students (almajirai) in Kano State in northern Nigeria. Moving to urban areas allows the young almajirai to escape difficult conditions and to access educational and income opportunities absent in their rural homes. It makes it possible for them to adopt self-conceptions as migrants in search of sacred knowledge who were once widely respected. However, economic decline has made survival in the city more difficult. Lacking the economic and cultural resources to participate in displays of status, and without social superiors to speak for them, the almajirai feel they have become fair game for those searching for scapegoats

Family functioning, parental psychological distress and child behaviours : evidence from the Victorian child health and wellbeing study

We examined, using data from the 2006 Victorian Child Health and Wellbeing Study (VCHWS), whether family functioning is associated with parental psychological distress and children&rsquo;s behavioural difficulties. The VCHWS was a statewide cross-sectional telephone survey to 5,000 randomly selected primary caregivers of 0- to 12-year-old children between October 2005 and March 2006. Only parents or guardians of children aged 4&ndash;12 years (n = 3,370) were included in this study. After adjusting for sociodemographic variables and ethnicity, parents or guardians scoring higher on the family functioning scale (i.e., from poorly functioning households) were at greater risk of psychological distress and had children with lower levels of prosocial behaviour and higher levels of behavioural difficulties relative to those from healthily functioning households. Mental health prevention programmes addressing child mental and conduct problems should consider the family environment and target those families functioning poorly.<br /

Characterization of the "deqi" response in acupuncture

<p>Abstract</p> <p>Background</p> <p>Acupuncture stimulation elicits <it>deqi</it>, a composite of unique sensations that is essential for clinical efficacy according to traditional Chinese medicine (TCM). There is lack of adequate experimental data to indicate what sensations comprise <it>deqi</it>, their prevalence and intensity, their relationship to acupoints, how they compare with conventional somatosensory or noxious response. The objective of this study is to provide scientific evidence on these issues and to characterize the nature of the <it>deqi phenomenon </it>in terms of the prevalence of sensations as well as the uniqueness of the sensations underlying the <it>deqi </it>experience.</p> <p>Methods</p> <p>Manual acupuncture was performed at LI4, ST36 and LV3 on the extremities in randomized order during fMRI in 42 acupuncture naïve healthy adult volunteers. Non-invasive tactile stimulation was delivered to the acupoints by gentle tapping with a von Frey monofilament prior to acupuncture to serve as a sensory control. At the end of each procedure, the subject was asked if each of the sensations listed in a questionnaire or any other sensations occurred during stimulation, and if present to rate its intensity on a numerical scale of 1–10. Statistical analysis including paired t-test, analysis of variance, Spearman's correlation and Fisher's exact test were performed to compare responses between acupuncture and sensory stimulation.</p> <p>Results</p> <p>The <it>deqi </it>response was elicited in 71% of the acupuncture procedures compared with 24% for tactile stimulation when thresholded at a minimum total score of 3 for all the sensations. The frequency and intensity of individual sensations were significantly higher in acupuncture. Among the sensations typically associated with <it>deqi</it>, aching, soreness and pressure were most common, followed by tingling, numbness, dull pain, heaviness, warmth, fullness and coolness. Sharp pain of brief duration that occurred in occasional subjects was regarded as inadvertent noxious stimulation. The most significant differences in the <it>deqi </it>sensations between acupuncture and tactile stimulation control were observed with aching, soreness, pressure and dull pain. Consistent with its prominent role in TCM, LI4 showed the most prominent response, the largest number of sensations as well as the most marked difference in the frequency and intensity of aching, soreness and dull pain between acupuncture and tactile stimulation control. Interestingly, the dull pain generally preceded or occurred in the absence of sharp pain in contrast to reports in the pain literature. An approach to summarize a sensation profile, called the <it>deqi composite</it>, is proposed and applied to explain differences in <it>deqi </it>among acupoints.</p> <p>Conclusion</p> <p>The complex pattern of sensations in the <it>deqi </it>response suggests involvement of a wide spectrum of myelinated and unmyelinated nerve fibers, particularly the slower conducting fibers in the tendinomuscular layers. The study provides scientific data on the characteristics of the <it>'deqi' </it>response in acupuncture and its association with distinct nerve fibers. The findings are clinically relevant and consistent with modern concepts in neurophysiology. They can provide a foundation for future studies on the <it>deqi </it>phenomenon.</p

The Genetic Basis of Hepatosplenic T-cell Lymphoma

Hepatosplenic T cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy number alterations in the disease. Chromatin modifying genes including SETD2, INO80 and ARID1B were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in STAT5B (31%), STAT3 (9%), and PIK3CD (9%) for which there currently exist potential targeted therapies. In addition, we noted less frequent events in EZH2, KRAS and TP53. SETD2 was the most frequently silenced gene in HSTL. We experimentally demonstrated that SETD2 acts as a tumor suppressor gene. In addition, we found that mutations in STAT5B and PIK3CD activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates novel gene mutations linked to HSTL pathogenesis and potential treatment targets

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

27th Annual Invitational Madrigal and Chamber Choir Festival

Program listing performers and works performe

War and challenges for contemporary criminology : an ethnography-inspired analysis of the narratives of unaccompanied young refugees with war experiences in institutional care in Sweden

This study concerns young people who have experienced war, taken shelter in Sweden, and been placed in institutions. The purpose of the study is to identify and analyze power relations that contribute to the shaping of young people’s identities and repertoires of action via stigmatizations and social comparisons with different reference groups. The study’s empirical material includes qualitatively oriented interviews with six young people from Iraq, Syria, and Afghanistan who have experienced war followed by placement in institutional care in Sweden. Analytical findings with the following themes are presented: (1) power relations and war, (2) power relations and escape from war, and (3) power relations and post war. The narratives on war and flight recounted by unaccompanied refugee minors describe the exercise of power in practice, in which wartime interactions (based on the exercise of power) are compared and related to peaceful interactions (in which there is no exercise of power). In this context, the interactive creation of contrasts and comparisons in relation to other actors reveals various categories of actor: victim, perpetrator, and hero.(Il)legal organizations and crime. Challenges for contemporary criminology. 21st Annual Conference of the European Society of Criminology, European Society of Criminology and University of Bucharest, Bucharest, Romania (20210908-20210911). ”War and challenges for contemporary criminology: an ethnography-inspired analysis of the narratives of unaccompanied young refugees with war experiences in institutional care in Sweden”, Goran Basic &amp; David Wästerfors. Youth with war experiences in institutional care. A sociological study of young immigrants' stigma and social comparison

Symbolic Interaction, Power, And War. An Ethnography-inspired Analysis Of The Narratives Of Unaccompanied Young Refugees With War Experiences In Institutional Care In Sweden

This study concerns young people who have experienced war, taken shelter in Sweden, and been placed in institutions. The purpose of the study is to identify and analyze power relations that contribute to the shaping of young people’s identities and repertoires of action via stigmatizations and social comparisons with different reference groups. The study’s empirical material includes qualitatively oriented interviews with six young people from Iraq, Syria, and Afghanistan who have experienced war followed by placement in institutional care in Sweden. Analytical findings with the following themes are presented: (1) power relations and war, (2) power relations and escape from war, and (3) power relations and post war. The study demonstrates that narratives about war, escaping war, and postwar life in Sweden construct and reconstruct an image of a series of interactive rituals that are both influenced by and influence the power dynamic between the actors. This relationship in turn creates and recreates an interplay among the stigmatizing experiences of the youths, their social comparisons, and definitions of inequality.Sociological Knowledges for Alternative Futures, the 15th European Sociological Association Conference, European Sociological Association, Autonomous University of Barcelona and Catalan Sociological Association, Barcelona, Spain (20210831-20210903). ”Symbolic interaction, power, and war: an ethnography-inspired analysis of the narratives of unaccompanied young refugees with war experiences in institutional care in Sweden”, Goran Basic &amp; David Wästerfors.Youth with war experiences in institutional care. A sociological study of young immigrants' stigma and social comparison