bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuron-recognizable characteristics of peptides recombined using a neuronal binding domain of botulinum neurotoxin
Authors: Kim Hye Rin , Jung Younghun , Shin Jonghyeok , Park Myungseo , Kweon Dae-Hyuk , Ban Choongjin 
Published: March 2022

AbstractRecombinant peptides were designed using the C-terminal domain (receptor binding domain, RBD) and its subdomain (peptide A2) of a heavy chain of botulinum neurotoxin A-type 1 (BoNT/A1), which can bind to the luminal domain of synaptic vesicle glycoprotein 2C (SV2C-LD). Peptide A2- or RBD-containing recombinant peptides linked to an enhanced green fluorescence protein (EGFP) were prepared by expression in Escherichia coli. A pull-down assay using SV2C-LD-covered resins showed that the recombinant peptides for CDC297 BoNT/A1, referred to EGFP-A2ʹ and EGFP-RBDʹ, exhibited ≥ 2.0-times stronger binding affinity to SV2C-LD than those for the wild-type BoNT/A1. Using bio-layer interferometry, an equilibrium dissociation rate constant (KD) of EGFP-RBDʹ to SV2C-LD was determined to be 5.45 μM, which is 33.87- and 15.67-times smaller than the KD values for EGFP and EGFP-A2ʹ, respectively. Based on confocal laser fluorescence micrometric analysis, the adsorption/absorption of EGFP-RBDʹ to/in differentiated PC-12 cells was 2.49- and 1.29-times faster than those of EGFP and EGFP-A2ʹ, respectively. Consequently, the recombinant peptides acquired reasonable neuron-specific binding/internalizing ability through the recruitment of RBDʹ. In conclusion, RBDs of BoNTs are versatile protein domains that can be used to mark neural systems and treat a range of disorders in neural systems.
Organization and dynamics of the SpoVAEa protein and its surrounding inner membrane lipids, upon germination of Bacillus subtilis spores
Authors: Wen Juan , Vischer Norbert O. E. , de Vos Arend L. , Manders Erik. M. M. , Setlow Peter , Brul Stanley 
Published: March 2022

AbstractThe SpoVA proteins make up a channel in the inner membrane (IM) of Bacillus subtilis spores. This channel responds to signals from activated germinant receptors (GRs), and allows release of Ca2+-DPA from the spore core during germination. In the current work, we studied the location and dynamics of SpoVAEa in dormant spores. Notably, the SpoVAEa-SGFP2 proteins were present in a single spot in spores, similar to the IM complex formed by all GRs termed the germinosome. However, while the GRs’ spot remains in one location, the SpoVAEa-SGFP2 spot in the IM moved randomly with high frequency. It seems possible that this movement may be a means of communicating germination signals from the germinosome to the IM SpoVA channel, thus stimulating CaDPA release in germination. The dynamics of the SpoVAEa-SGFP2 and its surrounding IM region as stained by fluorescent dyes were also tracked during spore germination, as the dormant spore IM appeared to have an immobile germination related functional microdomain. This microdomain disappeared around the time of appearance of a germinated spore, and the loss of fluorescence of the IM with fluorescent dyes, as well as the appearance of peak SpoVAEa-SGFP2 fluorescent intensity occurred in parallel. These observed events were highly related to spores’ rapid phase darkening, which is considered as due to rapid Ca2+DPA release. We also tested the response of SpoVAEa and the IM to thermal treatments at 40–80 °C. Heat treatment triggered an increase of green autofluorescence, which is speculated to be due to coat protein denaturation, and 80 °C treatments induce the appearance of phase-grey-like spores. These spores presumably have a similar intracellular physical state as the phase grey spores detected in the germination but lack the functional proteins for further germination events.
Local induction of regulatory T cells prevents inflammatory bone loss in ligature-induced experimental periodontitis in mice
Authors: Greene Ashlee C. , Shehabeldin Mostafa , Gao Jin , Balmert Stephen C. , Ratay Michelle , Sfeir Charles , Little Steven R. 
Published: March 2022

AbstractPeriodontitis (periodontal disease) is a highly prevalent disease, affecting over 65 million adults in the United States alone. Characterized by an overburden of invasive bacteria, gum inflammation and plaque buildup, over time, these symptoms can result in severe loss of gingival tissue attachment, bone resorption and even tooth loss. Although current treatments (local antibiotics and scaling and root planing procedures) target the bacterial dysbiosis, they do not address the underlying inflammatory imbalance in the periodontium. In the healthy steady state, the body naturally combats destructive, imbalanced inflammatory responses through regulatory pathways mediated by cells such as regulatory T cells (Tregs). Consequently, we hypothesized that local enrichment of regulatory lymphocytes (Tregs) could restore local, immunological homeostasis and prevent the main outcome of bone loss. Accordingly, we locally delivered a combination of TGFβ, Rapamycin, and IL2 microspheres in a ligature-induced murine periodontitis model. Herein, we have demonstrated this preventative treatment decreases alveolar bone loss, increases the local ratio of Tregs to T effector cells and changes the local microenvironment’s expression of inflammatory and regenerative markers. Ultimately, these Treg-inducing microspheres appear promising as a method to improve periodontitis outcomes and may be able to serve as a platform delivery system to treat other inflammatory diseases.
Mitochondrial dynamics in the neonatal brain – a potential target following injury?
Authors: Jones Adam , Thornton Claire 
Published: March 2022

AbstractThe impact of birth asphyxia and its sequelae, hypoxic–ischaemic (HI) brain injury, is long-lasting and significant, both for the infant and for their family. Treatment options are limited to therapeutic hypothermia, which is not universally successful and is unavailable in low resource settings. The energy deficits that accompany neuronal death following interruption of blood flow to the brain implicate mitochondrial dysfunction. Such HI insults trigger mitochondrial outer membrane permeabilisation leading to release of pro-apoptotic proteins into the cytosol and cell death. More recently, key players in mitochondrial fission and fusion have been identified as targets following HI brain injury. This review aims to provide an introduction to the molecular players and pathways driving mitochondrial dynamics, the regulation of these pathways and how they are altered following HI insult. Finally, we review progress on repurposing or repositioning drugs already approved for other indications, which may target mitochondrial dynamics and provide promising avenues for intervention following brain injury. Such repurposing may provide a mechanism to fast-track, low-cost treatment options to the clinic.
Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics
Authors: Brassington Kurt , Selemidis Stavros , Bozinovski Steven , Vlahos Ross 
Published: March 2022

AbstractChronic obstructive pulmonary disease (COPD) and atherosclerosis are chronic irreversible diseases, that share a number of common causative factors including cigarette smoking. Atherosclerosis drastically impairs blood flow and oxygen availability to tissues, leading to life-threatening outcomes including myocardial infarction (MI) and stroke. Patients with COPD are most likely to die as a result of a cardiovascular event, with 30% of all COPD-related deaths being attributed to cardiovascular disease (CVD). Both atherosclerosis and COPD involve significant local (i.e. lung, vasculature) and systemic inflammation and oxidative stress, of which current pharmacological treatments have limited efficacy, hence the urgency for the development of novel life-saving therapeutics. Currently these diseases must be treated individually, with no therapies available that can effectively reduce the likelihood of comorbid CVD other than cessation of cigarette smoking. In this review, the important mechanisms that drive atherosclerosis and CVD in people with COPD are explained and we propose that modulation of both the oxidative stress and the inflammatory burden will provide a novel therapeutic strategy to treat both the pulmonary and systemic manifestations related to these diseases.
Evaluating the Effect of Rich Vocabulary Instruction and Retrieval Practice on the Classroom Vocabulary Skills of Children With (Developmental) Language Disorder
Authors: Levlin Maria , Wiklund-Hörnqvist Carola , Sandgren Olof , Karlsson Sara , Jonsson Bert 
Published: March 2022

Purpose:Learning new vocabulary has been identified as a challenge for students with (developmental) language disorder ((D)LD). In this study, we evaluate the effects of two active learning methods, (a) retrieval practice (RP) and (b) rich vocabulary instruction (RVI), in a group of students with (D)LD in secondary school.Method:A quasi-experimental counterbalanced within-subject design was used to compare and evaluate the effect of RP and RVI on learning Tier 2 vocabulary, with target and control words as dependent measures. Eleven students with (D)LD (Mage= 14.9 years) attending a language unit participated. RP and RVI were implemented in regular classroom activities during 16 lessons (eight lessons/instructional condition). Learning was assessed by comparing performance on a pretest session 1–2 weeks prior, with posttest performance 1 week after each instructional condition.Results:The learning gain for RP was superior to that for RVI, both with respect to the Bayesian probabilistic estimations for target words relative to control words and in direct comparison with RVI. Only weak evidence was found for RVI with respect to the Bayesian probabilistic estimations for target words relative to control words.Conclusions:All participants showed positive learning gains following RP, whereas the outcome for RVI was more diverse. This initial work suggests that RP promotes larger learning gains relative to RVI and promotes learning across language profiles. This study extends previous studies by exploring the implementation of RP in regular classroom activities and by using more complex to-be-learned material (Tier 2 words).
Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells
Authors: Zhou Zhihong , Liu Shangjun 
Published: March 2022

AbstractMaprotiline is an antidepressant that has been found to cause hypoglycemia. However, the effect of maprotiline on diabetic nephropathy (DN) has not been investigated. Here, we explored the effect of maprotiline on human renal glomerular endothelial cells (HRGECs) in response to high glucose (HG) stimulation. We found that maprotiline attenuated HG-induced oxidative stress in HRGECs with decreased reactive oxygen species production and increased superoxide dismutase activity. Maprotiline repressed the HG-induced expression of cyclooxygenases 2 at both mRNA and protein levels in HRGECs. The increased thromboxane B2 level and decreased 6-keto-prostaglandin F1α level induced by HG were significantly attenuated by maprotiline treatment. Maprotiline also prevented the HG-induced increase in the permeability of HRGECs and the decrease in the zonula occludens-1 expression and downregulated HG-induced increase in the expression of protein kinase C-α (PKC-α) in HRGECs. This protective effect of maprotiline on HG-induced HRGECs dysfunction was abolished by overexpression of PKC-α. In conclusion, maprotiline displayed a protective effect on HG-challenged HRGECs, which was mediated by the regulation of PKC-α. These findings provide further evidence for the potential use of maprotiline for the treatment of DN.
Effects of B12 Deficiency Anemia on Radial Peripapillary and Macular Vessel Density: An Optical Coherence Tomography Angiography (OCTA) Study
Authors: Koca Semra , Bozkurt Erhan , Dogan Mustafa , Yavasoglu Filiz , Erogul Özgür , Bulut Ayten Kocaman 
Published: March 2022

Abstract
Background To evaluate the macular and optic disc vascular changes in vitamin B12 deficiency anemia.
Methods A total of 24 patients with vitamin B12 deficiency anemia and 24 healthy controls were involved in this study. All participants were evaluated for central macular thickness
(CMT), peripapillary retina nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, macular vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus
(DCP), choriocapillaris flow area, and optic disc radial peripapillary capillary (RPC) VD using optic coherence tomography (OCT) and optic coherence tomography angiography (OCTA). Metabolic
parameters were also noted.
Results Temporal RNFL thickness significantly decreased in the B12 deficiency anemia group (p = 0.04). Choriocapillaris flow area (p = 0.045) and macular vessel density in both SCP
(p = 0.022) and DCP (p = 0.018) markedly declined in the study group. Optic disc RPC VD in the B12 deficiency anemia group was lower in all regions compared to that of the control group, but
the difference was not statistically significant (p > 0.05). There were significant positive correlations between choriocapillaris flow area, macular VD, vitamin B12, and hemoglobin.
Conclusion Retinal vascular alterations were observed in B12 deficiency anemia, and OCTA may be beneficial in the diagnosis and follow-up of ocular complications in these cases.
Eine Fallserie wacher Glaukomoperationen mittels Sub-Tenon- oder subkonjunktivaler Anästhesie bei älteren PatientInnen mit Aortenklappenstenose
Authors: Lersch Friedrich , Harte Johannes , Ugen Gesar , Kuonen Astrid 
Published: March 2022

ZusammenfassungBei zunehmender Alterung unserer Gesellschaft behandeln AnästhesistInnen und AugenchirurgInnen zusehends mehr GlaukompatientInnen, die gleichzeitig an Aortenklappenstenose (AKS) leiden. In
der chirurgischen und anästhesiologischen Therapie erfordert diese Konstellation eine anspruchsvolle gemeinsame Herangehensweise. Wir berichten über 6 Fälle von AKS-PatientInnen, die sich
einer Glaukomoperation in Sub-Tenon-Block oder subkonjunktivaler Anästhesie unterzogen haben. Dabei musste einer Patientin mit intraoperativen Schmerzen wiederholt eine subkonjunktivale
Lokalanästhesie gegeben werden. Die Patientin war anhaltend hypertensiv und es kam zu einer umschriebenen Choroidalblutung. Das komplizierte Follow-up war geprägt durch exorbitante
intraokulare Druckschwankungen und einer sekundären Choroidalblutung. Anästhesiologie und Ophthalmochirurge müssen ihre Strategie aufeinander abstimmen, um den optimalen transmuralen Druck
über die choroidalen Gefäße, aber auch den stenotischen aortalen Ausflusstrakt gewährleisten zu können. Oftmals sind den Klinikern die pathophysiologischen Kernkonzepte der Partnerdisziplin
nicht geläufig. Die Diskussion unserer Fallserie erörtert die differenzierte Herangehensweise beider beteiligter Disziplinen, Pathophysiologie der AKS und der choroidalen Blutung und
besonders jene Arbeitsschritte und therapeutischen Entscheidungen, die zur Sicherheit solcher Hochrisikopatienten gemeinsam angegangen werden müssen.
Analysis of the Thickness of the Outer Retinal Layer Using Optical Coherence Tomography – A Predictor of Visual Acuity in Schizophrenia
Authors: Bozali Erman , Yalinbas Duygu 
Published: March 2022

Abstract
Background The aim of this study was to evaluate the thickness of the outer retinal layer (ORL) together with macular thickness and changes in the retinal nerve fiber layer (RNFL) in
patients with schizophrenia in comparison with healthy controls.
Methods This study included 114 eyes of 57 patients diagnosed with schizophrenia and 114 eyes of 57 healthy controls. Central foveal thickness (CFT), central macular thickness (CMT),
and ORL thickness were measured in both groups via the images obtained by spectral-domain optical coherence tomography (SD-OCT). RNFL was also assessed in four quadrants (inferior, superior,
temporal, nasal). CMT measurements were presented as the average thickness of the macula in the central 1 mm area on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The ORL
thickness was defined as the distance between the external limiting membrane and retinal pigment epithelium at the center of the foveal pit.
Results The mean age of 57 patients was 37 ± 10 years, of whom 34 (60%) were male and 23 (40%) female. No statistically significant difference was found between groups in terms of
age and gender (p = 0.8 for age, p = 0.9 for gender). There was no statistically significant difference in the mean CMT between the two groups (p = 0.1). The mean ORL thickness in the two
groups was 99.8 ± 8.3 and 103.7 ± 6.2, respectively, and was significantly decreased in the schizophrenia group (p = 0.005). RNFL analysis demonstrated significant thinning in the inferior
and superior quadrants compared to healthy controls (p < 0.001 and p = 0.017, respectively).
Conclusions SD-OCT findings – especially ORL and RNFL thickness – may be related to the neurodegenerational changes in schizophrenia.
Immuntherapie bei Brustkrebs
Authors: Würstlein Rachel , Harbeck Nadia 
Published: March 2022

ZusammenfassungWährend bei anderen soliden Tumoren Immuntherapie seit Jahren zum
Therapiestandard gehört, steht sie bei Brustkrebs noch ganz am Anfang.
Klinisch relevant ist sie beim triple-negativen Mammakarzinom (TNBC). Seit 2019
ist der PD-L1-Inhibitor (PD-L1: Programmed death-ligand 1) Atezolizumab als
Erstlinientherapie beim metastasierten TNBC zugelassen. Vielversprechende Daten
gibt es auch zur neoadjuvanten Therapie bei TNBC sowohl für Atezolizumab
als auch für den PD1-Inhibitor Pembrolizumab. Studien beim luminalen
frühen Mammakarzinom laufen derzeit. Eine kommentierte
Übersicht.
Ultrastructural Examination of the Corneal Interface after Predescemetic Deep Anterior Lamellar Keratoplasty (DALK) – A Case Report with Light and Transmission Electron
Microscopy
Authors: Berger Tim , Seitz Berthold , Hamon Loïc , Flockerzi Fidelis , Schlötzer-Schrehardt Ursula , Daas Loay 
Published: March 2022

Abstract
Purpose To examine corneal buttons with light and transmission electron microscopy (TEM) to visualize the interface area and highlight the ultrastructural corneal changes after deep
anterior lamellar keratoplasty (DALK).
Methods Two patients underwent excimer laser-assisted penetrating repeat keratoplasty after predescemetic DALK. The corneal buttons were examined by light microscopy and TEM.
Results The light microscopic examination of the corneal buttons revealed fragments of a second Descemetʼs membrane in the central and midperipheral areas (Case 1). In both cases,
visualization of the interface area was not possible by light microscopy. The donor and host stroma were tightly attached without dehiscence. TEM identified the interface area by
irregularities in the collagen distribution between the donor and host stroma. The thickness of the remaining recipient corneal stroma measured approximately 30 µm (Case 1) and 100 µm (Case
2), respectively. In the host stroma, TEM revealed the absence or degeneration of keratocytes, accumulation of amorphous material between the collagen lamellae, and vacuolar inclusions
dispersed in the stroma, forming a band-like zone anterior to Descemetʼs membrane.
Conclusion The interface area after DALK has been mainly investigated by in vivo confocal microscopy. Light microscopy and TEM findings indicate remodeling processes after
DALK that are associated with increased keratocyte degeneration and structural alterations of the extracellular matrix in the host stroma. The choice of surgical method may influence the
postoperative morphological and functional outcome since these findings were primarily apparent in the remaining host stroma. Therefore, complete exposure of Descemetʼs membrane is an
important prognostic factor for the postoperative visual outcome.
New Paradigms for Familiar Diseases: Lessons Learned on Circulatory
Bacterial Signatures in Cardiometabolic Diseases
Authors: Chakaroun Rima , Massier Lucas , Musat Niculina , Kovacs Peter 
Published: March 2022

AbstractDespite the strongly accumulating evidence for microbial signatures in metabolic
tissues, including the blood, suggesting a novel paradigm for metabolic disease
development, the notion of a core blood bacterial signature in health and
disease remains a contentious concept. Recent studies clearly demonstrate that
under a strict contamination-free environment, methods such as 16 S rRNA
gene sequencing, fluorescence in-situ hybridization, transmission electron
microscopy, and several more, allied with advanced bioinformatics tools, allow
unambiguous detection and quantification of bacteria and bacterial DNA in human
tissues. Bacterial load and compositional changes in the blood have been
reported for numerous disease states, suggesting that bacteria and their
components may partially induce systemic inflammation in cardiometabolic
disease. This concept has been so far primarily based on measurements of
surrogate parameters. It is now highly desirable to translate the current
knowledge into diagnostic, prognostic, and therapeutic approaches.This review addresses the potential clinical relevance of a blood bacterial
signature pertinent to cardiometabolic diseases and outcomes and new avenues for
translational approaches. It discusses pitfalls related to research in low
bacterial biomass while proposing mitigation strategies for future research and
application approaches.
Zwanghaftes Zweifeln als philosophisch-psychopathologisches Phänomen
Authors: Mavrogiorgou Paraskevi , Juckel Georg 
Published: March 2022

ZusammenfassungZwanghaftes Zweifeln (zZ) ist ein eher vergessenes und unterschätztes psychopathologisches Phänomen, obgleich er klinisch bei vielen Patienten mit einer Zwangsstörung vorhanden zu sein scheint. Die wenige vorhandene vor allem psychoanalytische und kognitionswissenschaftliche Literatur zum zZ erklärt das Phänomen nicht vollständig und bietet darüber hinaus nur wenig an Behandlungsperspektiven. Hier soll ein anderer Weg vorgeschlagen werden. Das dem Menschen gehörige Zweifeln an der Wahrnehmung von Objekten, Anderen und sich selbst steigert sich als zZ ins Pathologische. Zweifeln wird als ein existenzielles Problem des Menschen angesehen, das als solches zu den Grundfragen der Philosophie seit ihren Anfängen, speziell zum Skeptizismus gehört. Wenn bzgl. dieses Zweifelns Gegengründe gefunden werden könnten, würden sich für die Behandlung von Patienten mit zZ mentale Lösungsstrategien im Rahmen theoretisch vertiefter Psychotherapie einschließlich kognitiver Übungsansätze ergeben.
Synthesis of Diaza[5]helicenes by ortho,ortho′-Fusion of ortho-Terphenyls
Authors: Podlech Joachim , Herzog Stefan , Marten Inka , Weiß Aaron 
Published: March 2022

AbstractDouble ortho-fusion in suitably substituted ortho-terphenyls was used for the synthesis of diaza[5]helicenes. Bis(carboxamido)-substituted ortho-terphenyls can be condensed to 5,9- and 6,9-diaza[5]helicenes, where substituents at the 6,10- and 5,10-positions, respectively­, are introduced with the carboxamido groups. While a twofold­ coupling sequence with intermediate protection of one amino group has to be used for 5,9-diaza[5]helicenes, a more concise sequence avoiding the protection leads to 6,9-diaza[5]helicenes. The simple heating of ortho,ortho′-diazidoterphenyls furnishes 5,8-dihydroindolo[2,3-c]carbazoles, i.e., [5]helicenes with alternating benzene and pyrrole rings.