Making the Move: Migrating the Boston College Law School Library

Moving an institutional repository is no small feat. There are costs and benefits to every platform and to the migration process itself. However, Boston College Law Library\u27s partnership with Ubiquity Press has shown that this process can be approachable and create opportunities for improvement and growth of the repository. Members of the Boston College Law Library team will describe our decision process behind making the choice to move and selecting our new platform, outline the migration process itself, and discuss some of the changes that were enabled by this move to improve and modernize our repository

Context-Specific, User-Centred: Designing Urban Green Infrastructure to Effectively Mitigate Urban Density and Heat Stress

Green infrastructure plays a vital role for cities facing the challenges of urbanisation and climate change. It has the potential to mitigate the adverse effects of urban density and the heat island effect, enhancing the ecological and social resilience of cities and their inhabitants. This study identifies contextual, psychological, and social factors which influence people’s subjective evaluation of urban green infrastructure (UGI), density, and heat stress. Planning recommendations for effective, context-specific, user-centred design are developed to increase the social and health benefits of UGI in limited space. To do so, a mixed-methods approach that combines social surveys, GIS-analysis, and microclimate modelling was employed. The field studies were undertaken in two contrasting neighbourhoods in Munich, Germany: a densely built and scarcely vegetated inner-city neighbourhood and a declaimed “green and compact” neighbourhood at the outskirts. Both sites are assessed in terms of their supply of green infrastructure, building and population density, and outdoor summer heat loads drawing on geostatistical data and mean radiant temperature modelling. This assessment is compared to the inhabitants’ subjective evaluation thereof retrieved from face-to-face questionnaires, and semi-standardised interviews. The results indicate that the existence and the amount of UGI per se are not decisive for people’s perception of urban heat, density, and neighbourhood attractiveness. It is rather the perceived accessibility of green spaces, their design, quality, and contextual factors like traffic or the presence of other people that define its value for urban dwellers

Nanomedicine-driven molecular targeting, drug delivery, and therapeutic approaches to cancer chemoresistance

Cancer cell resistance to chemotherapeutics (chemoresistance) poses a significant clinical challenge that oncology research seeks to understand and overcome. Multiple anticancer drugs and targeting agents can be incorporated in nanomedicines, in addition to different treatment modalities, forming a single nanoplatform that can be used to address tumor chemoresistance. Nanomedicine-driven molecular assemblies using nucleic acids, small interfering (si)RNAs, miRNAs, and aptamers in combination with stimuli-responsive therapy improve the pharmacokinetic (PK) profile of the drugs and enhance their accumulation in tumors and, thus, therapeutic outcomes. In this review, we highlight nanomedicine-driven molecular targeting and therapy combination used to improve the 3Rs (right place, right time, and right dose) for chemoresistant tumor therapies

Polymorphism in COMT is associated with IgG 3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome

Background Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor- associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI. Methods We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA. Results Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG 3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI. Conclusion Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS

Cilostazol promotes blood vessel formation and bone regeneration in a murine non-union model

Non-unions represent a major complication in trauma and orthopedic surgery. Many factors contribute to bone regeneration, out of which an adequate vascularization has been recognized as crucial. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in a variety of preclinical studies. Hence, we herein investigated the effects of cilostazol on bone regeneration in an atrophic non-union model in mice. For this purpose, a 1.8 mm femoral segmental defect was stabilized by pin-clip fixation and the animals were treated daily with 30 mg/kg body weight cilostazol or saline (control) per os. At 2, 5 and 10 weeks after surgery the healing of femora was analyzed by X-ray, biomechanics, photoacoustic imaging, and micro-computed tomography (µCT). To investigate the cellular composition and the growth factor expression of the callus tissue additional histological, immunohistochemical and Western blot analyses were performed. Cilostazol-treated animals showed increased bone formation within the callus, resulting in an enhanced bending stiffness when compared to controls. This was associated with a more pronounced expression of vascular endothelial growth factor (VEGF), a higher number of CD31-positive microvessels and an increased oxygen saturation within the callus tissue. Furthermore, cilostazol induced higher numbers of tartrate-resistant acidic phosphate (TRAP)-positive osteoclasts and CD68-positive macrophages. Taken together, these findings demonstrate that cilostazol is a promising drug candidate for the adjuvant treatment of atrophic non-unions in clinical practice

Help-seeking attitudes and behaviours for mental health problems in adolescents before and during the first COVID-19 school closures in Germany.

AIM Comparing measures of psychological wellbeing and help-seeking in youths before and within the first school closures due to the coronavirus disease 2019 (COVID-19) pandemic enables a better understanding of the effects the pandemic has for those seeking professional help for mental health problems. METHODS Data were obtained from the Germany-based ProHEAD school study. Pre-lockdown and lockdown samples (n = 648) were compared regarding pupils' psychological wellbeing, help-seeking attitudes and help-seeking behaviour. RESULTS Participants from the lockdown sample showed greater positive attitudes towards seeking professional help, whereas psychological wellbeing and help-seeking behaviour remained stable. CONCLUSIONS Possible explanations may include an increased public discourse on mental health or self-selection bias for participation during lockdown

Moderators of pre-post changes in school-based mental health promotion: Psychological stress symptom decrease for adolescents with mental health problems, knowledge increase for all.

Background School-based mental health promotion aims to strengthen mental health and reduce stress. Results on the effectiveness of such programs are heterogeneous. This study realized a school-based mental health promotion program (StresSOS) for all students and aimed to identify moderators (mental health status, gender, grade level) of pre- to post-changes in stress symptoms and knowledge. Methods Participants were N = 510 adolescents (from 29 classes; 46.7% female) aged 12-18 years (M = 13.88, SD = 1.00; grade levels 7-10). They were without mental health problems (65.9%), at risk for mental health problems (21.6%), or with mental health problems (12.5%) and participated in a 90 min per week face-to-face training with 8 sessions in class at school. Demographic variables, mental health status, stress symptoms, and knowledge about stress and mental health were collected at baseline. Program acceptance, stress symptoms, and knowledge were collected post-intervention. Multilevel mixed effects models were conducted with the fixed effects time (within factor), mental health status, gender, and grade level (between factors). Random effects for students within classes were included. Results In the pre-post comparison, mental health status moderated the changes on psychological stress symptoms (p < 0.05). In adolescents with mental health problems the largest reduction in stress symptoms was observed between pre- and post-assessment. Gender and grade level were less relevant. For all adolescents knowledge gains were revealed (p < 0.001). Program acceptance was moderated by mental health status and grade level (p < 0.01). Mentally healthy adolescents and within the group of adolescents at-risk or with mental health problems, especially younger students (7th/8th grade), rated program acceptance higher. Conclusion Psychological stress symptoms decreased among adolescents with mental health problems and not among adolescents at risk for or without mental health problems. Mental health-related knowledge increased for all adolescents. The results add to knowledge on school-based mental health intervention research and practice. Its implications for different prevention strategies (universal, selective or a combination of both) are discussed

Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation

Mouse cells package heterochromatin into compact foci. Erdel et al. show that these foci lack hallmarks of liquid droplets and rather resemble collapsed polymer globules. Their size, accessibility, and compaction are independent of HP1. They can adopt two distinct folding states that possibly represent the fundamental modes of chromatin compaction

The Nucleoside Diphosphate Kinase Gene Nme3 Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance

The t-haplotype, a variant form of the t-complex region on mouse chromosome 17, acts as selfish genetic element and is transmitted at high frequencies (>95%) from heterozygous (t/+) males to their offspring. This phenotype is termed transmission ratio distortion (TRD) and is caused by the interaction of the t-complex responder (Tcr) with several quantitative trait loci (QTL), the t-complex distorters (Tcd1 to Tcd4), all located within the t-haplotype region. Current data suggest that the distorters collectively impair motility of all sperm derived from t/+ males; t-sperm is rescued by the responder, whereas +-sperm remains partially dysfunctional. Recently we have identified two distorters as regulators of RHO small G proteins. Here we show that the nucleoside diphosphate kinase gene Nme3 acts as a QTL on TRD. Reduction of the Nme3 dosage by gene targeting of the wild-type allele enhanced the transmission rate of the t-haplotype and phenocopied distorter function. Genetic and biochemical analysis showed that the t-allele of Nme3 harbors a mutation (P89S) that compromises enzymatic activity of the protein and genetically acts as a hypomorph. Transgenic overexpression of the Nme3 t-allele reduced t-haplotype transmission, proving it to be a distorter. We propose that the NME3 protein interacts with RHO signaling cascades to impair sperm motility through hyperactivation of SMOK, the wild-type form of the responder. This deleterious effect of the distorters is counter-balanced by the responder, SMOKTcr, a dominant-negative protein kinase exclusively expressed in t-sperm, thus permitting selfish behaviour and preferential transmission of the t-haplotype. In addition, the previously reported association of NME family members with RHO signaling in somatic cell motility and metastasis, in conjunction with our data involving RHO signaling in sperm motility, suggests a functional conservation between mechanisms for motility control in somatic cells and spermatozoa