bluuebunny/crossref_metadata_2025 huggingface dataset:
Der lange Weg zum Psychotherapeutengesetz
Authors: Schulte Dietmar
Published: July 2021

Zusammenfassung. In diesem Beitrag soll die wechselhafte Geschichte des Gesetzes anhand historischer Quellen sowie eigener Unterlagen und Erinnerungen nachvollzogen werden. Dabei ergeben sich fünf historische Phasen. Zeit des Aufbruchs: In den 1960er Jahren traten durch die Entwicklung der Verhaltenstherapie als einem psychologischen Therapieansatz wesentliche Veränderungen des Selbstverständnisses und der Tätigkeitsbereiche der Klinischen Psychologen ein. Der BDP beschließt, eine gesetzliche Regelung für eine selbstständige Tätigkeit eines „Fachpsychologen für Klinische Psychologie“ anzustreben. 1973 empfiehlt die Psychiatrie Enquete-Kommission ein Gesetz für nichtärztliche Psychotherapeuten als eine der Sofortmaßnahmen. Erster Anlauf (1974 – 1978): Die Bundesregierung beginnt 1974 mit der Arbeit. Die Grundzüge werden allgemein begrüßt. Als erst vier Jahre später der Referentenentwurf vorgestellt wird, wird dieser jedoch mehrheitlich abgelehnt. „Interregnum“ (1978 – 1989): Das BMG stellt die Arbeit am Gesetz ein. Das Bundessozialministerium unternimmt seinerseits Maßnahmen zur Verbesserung der psychotherapeutischen Versorgung. Die Verhaltenstherapie wird Kassenleistung und die KBV fördert und akkreditiert private Ausbildungsinstitute für Verhaltenstherapie. Parallel dazu fördert die Föderation Deutscher Psychologenverbände universitäre Weiterbildungsgänge und akkreditiert diese. Ein von Gesundheitsministerin Ursula Lehr beauftragtes Gutachten empfiehlt 1991 ein Gesetz. Dies zieht Abwehrreaktionen der Ärzteschaft nach sich. Zweiter Anlauf (1993 – 1995): Das BMG beginnt erneut mit der Arbeit, intensiv begleitet von den inzwischen vielfältigen Berufs-und Fachverbänden. Das Gesetz scheitert im Bundesrat an der sogenannten Zuzahlungsregelung. Dritter Anlauf (1996 – 1999): 1997 beginnt das BMG erneut mit der Arbeit, beschränkt auf das Sozialrecht. Die Zuzahlungsregelung wird in einem gesonderten Gesetz geregelt. Am 06.03.98 stimmt als letzte Instanz der Bundesrat zu; der Einspruch gegen das Zuzahlungsgesetz wird mit einer Stimme Mehrheit abgelehnt.
Rising Seas, Rising Inequity? Communities at Risk in the San Francisco Bay Area and Implications for Adaptation Policy
Authors: Bick I. Avery , Santiago Tate Adrian F. , Serafin Katherine A. , Miltenberger Alex , Anyansi Ifeoma , Evans Max , Ortolano Leonard , Ouyang Derek , Suckale Jenny
Published: July 2021

Increasing coastal flooding threatens urban centers worldwide. Projections of physical damages to structures and their contents can characterize the monetary scale of risk, but they lack relevant socioeconomic context. The impact of coastal flooding on communities hinges not only on the cost, but on the ability of households to pay for the damages. Here, we repurpose probabilistic risk assessment to analyze the monetary and social risk associated with coastal flooding in the San Francisco Bay Area for 2020–2060. We show that future coastal flooding could financially ruin a substantial number of households by burdening them with flood damage costs that exceed discretionary household income. We quantify these impacts at the census block group scale by computing the percentage of households without discretionary income, before and after coastal flooding costs. We find that for several coastal communities in San Mateo County more than 50% of households will be facing financial instability, highlighting the need for immediate policy interventions that target existing, socially produced risk rather than waiting for potentially elusive certainty in sea level rise projections. We emphasize that the percentage of financially unstable households is particularly high in racially diverse and historically disadvantaged communities, highlighting the connection between financial instability and inequity. While our estimates are specific to the San Francisco Bay Area, our granular, household‐level perspective is transferable to other urban centers and can help identify the specific challenges that different communities face and inform appropriate adaptation interventions.
Geologic History and Crater Morphology of Asteroid (162173) Ryugu
Authors: Cho Y. , Morota T. , Kanamaru M. , Takaki N. , Yumoto K. , Ernst C. M. , Hirabayashi M. , Barnouin O. S. , Tatsumi E. , Otto K. A. , Schmitz N. , Wagner R. J. , Jaumann R. , Miyamoto H. , Kikuchi H. , Hemmi R. , Honda R. , Kameda S. , Yokota Y. , Kouyama T. , Suzuki H. , Yamada M. , Sakatani N. , Honda C. , Hayakawa M. , Yoshioka K. , Matsuoka M. , Michikami T. , Hirata N. , Sawada H. , Ogawa K. , Sugita S.
Published: July 2021

Crater morphology and surface age of asteroid (162173) Ryugu are characterized using the high‐resolution images obtained by the Hayabusa2 spacecraft. Our observations reveal that the abundant boulders on and under the surface of the rubble‐pile asteroid affect crater morphology. Most of the craters on Ryugu exhibit well‐defined circular depressions, unlike those observed on asteroid Itokawa. The craters are typically outlined by boulders remaining on the rim. Large craters (diameter > 100 m) host abundant and sometimes unproportionally large boulders on their floors. Small craters (<20 m) are characterized by smooth circular floors distinguishable from the boulder‐rich exterior. Such small craters tend to have dark centers of unclear origin. The correlation between crater size and boulder number density suggests that some processes sort the size of boulders in the shallow (<30 m) subsurface. Furthermore, the crater size‐frequency distributions (CSFDs) of different regions on Ryugu record multiple geologic events, revealing the diverse geologic history on this 1‐km asteroid. Our crater‐counting analyses indicate that the equatorial ridge is the oldest structure of Ryugu and was formed 23–30 Myr ago. Then, Ryugu was partially resurfaced, possibly by the impact that formed the Urashima crater 5–12 Myr ago. Subsequently, a large‐scale resurfacing event formed the western bulge and the fossae 2–9 Myr ago. Following this process, the spin of Ryugu slowed down plausibly due to the YORP effect. The transition of isochrons in a CSFD suggests that Ryugu was decoupled from the main belt and transferred to a near‐Earth orbit 0.2–7 Myr ago.
Ionospheric Electron Density and Conductance Changes in the Auroral Zone During Substorms
Authors: Stepanov N. A. , Sergeev V. A. , Shukhtina M. A. , Ogawa Y. , Chu X. , Rogov D. D.
Published: July 2021

Enhanced precipitation of magnetospheric energetic electrons during substorms increases ionospheric electron density and conductance. Such enhancements, which have timescales of a few hours, are not reproduced by the existing ionospheric models. We use the linear prediction filter (LPF) method to reconstruct the substorm‐related response of electron densities and integral conductances from long‐term ionospheric observations made by the European Incoherent SCATer radar located at Tromsø. To characterize the intensity of substorm dipolarization at a 5 min time step, we use the midlatitude positive bay index. We build response functions (LP filters) as a function of substorm time between T0−1 h and T0 + 4 h (T0 is a substorm onset time) in different magnetic local time (MLT) sectors to estimate the magnitude and delays of the ionospheric density response at different altitudes. Systematic and large relative changes are mostly observed in the D‐ and E regions. The duration of the response is about 3 h. It starts and reaches maximum magnitude near midnight, propagating from there toward the east and decaying after passing into the noon‐evening sector. The reliability of LPF results is confirmed by the consistency of D‐region response with independently derived response of the auroral absorption. Whereas strong ionization increases are seen in both E‐ and D‐regions on the nightside, the D‐region response is stronger in the morning‐dayside sector. Such MLT variation corresponds to the drift motion and precipitation of the high‐energy electrons injected in the nightside magnetosphere during substorm dipolarization. The inferred ionization changes result in strong enhancements of integral Hall (and Pedersen) conductance in the nightside auroral zone, where intense auroral currents are known to occur during substorms
Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms
Authors: Bagautdinova Joëlle , Zöller Daniela , Schaer Marie , Padula Maria Carmela , Mancini Valentina , Schneider Maude , Eliez Stephan
Published: July 2021

Schizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1–6 time points were collected from 324 participants aged 5–35 years (N = 148 22q11DS, N = 176 controls), resulting in a total of 636 scans (N = 334 22q11DS, N = 302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N = 61, 146 scans), or remained exempt of (N = 47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in frontotemporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly frontotemporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.
Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens
Authors: Kim Hee-Dae , Wei Jing , Call Tanessa , Quintus Nicole Teru , Summers Alexander J. , Carotenuto Samantha , Johnson Ross , Ma Xiaokuang , Xu Chenxi , Park Jin G. , Qiu Shenfeng , Ferguson Deveroux
Published: July 2021

Depression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.
Wet-dry cycles protect surface-colonizing bacteria from major antibiotic classes
Authors: Beizman-Magen Yana , Grinberg Maor , Orevi Tomer , Kashtan Nadav
Published: July 2021

Diverse antibiotic compounds are abundant in microbial habitats undergoing recurrent wet-dry cycles, such as soil, root and leaf surfaces, and the built environment. These antibiotics play a central role in microbial warfare and competition, thus affecting population dynamics and the composition of natural microbial communities. Yet, the impact of wet-dry cycles on bacterial response to antibiotics has been scarcely explored. Using the bacterium E. coli as a model organism, we show through a combination of experiments and computational modeling, that wet-dry cycles protect bacteria from beta-lactams. This is due to the combined effect of several mechanisms including tolerance induced by high salt concentrations and slow cell-growth, which are inherently associated with microscopic surface wetness—a hydration state typical to ‘dry’ periods. Moreover, we find evidence for a cross-protection effect, where lethal doses of antibiotic considerably increase bacterial survival during the dry periods. This work focuses on beta-lactams, yet similar protection was observed for additional major antibiotic classes. Our findings shed new light on how we understand bacterial response to antibiotics, with broad implications for population dynamics, interspecies interactions, and the evolution of antibiotic resistance in vast terrestrial microbial habitats.
Biosynthetic potential of uncultured Antarctic soil bacteria revealed through long-read metagenomic sequencing
Authors: Waschulin Valentin , Borsetto Chiara , James Robert , Newsham Kevin K , Donadio Stefano , Corre Christophe , Wellington Elizabeth
Published: July 2021

The growing problem of antibiotic resistance has led to the exploration of uncultured bacteria as potential sources of new antimicrobials. PCR amplicon analyses and short-read sequencing studies of samples from different environments have reported evidence of high biosynthetic gene cluster (BGC) diversity in metagenomes, indicating their potential for producing novel and useful compounds. However, recovering full-length BGC sequences from uncultivated bacteria remains a challenge due to the technological restraints of short-read sequencing, thus making assessment of BGC diversity difficult. Here, long-read sequencing and genome mining were used to recover >1400 mostly full-length BGCs that demonstrate the rich diversity of BGCs from uncultivated lineages present in soil from Mars Oasis, Antarctica. A large number of highly divergent BGCs were not only found in the phyla Acidobacteriota, Verrucomicrobiota and Gemmatimonadota but also in the actinobacterial classes Acidimicrobiia and Thermoleophilia and the gammaproteobacterial order UBA7966. The latter furthermore contained a potential novel family of RiPPs. Our findings underline the biosynthetic potential of underexplored phyla as well as unexplored lineages within seemingly well-studied producer phyla. They also showcase long-read metagenomic sequencing as a promising way to access the untapped genetic reservoir of specialised metabolite gene clusters of the uncultured majority of microbes.
Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation
Authors: Luft Thomas , Dreger Peter , Radujkovic Aleksandar
Published: July 2021

Allogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.
TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling
Authors: Yang Wanlei , Lu Xuanyuan , Zhang Tan , Han Weiqi , Li Jianlei , He Wei , Jia Yewei , Zhao Kangxian , Qin An , Qian Yu
Published: July 2021

Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo signaling pathway; it was suggested to be involved in the regulation of bone homeostasis. However, the exact role of TAZ in osteoclasts has not yet been established. In this study, we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation, which was further evidenced by in vitro osteoclast formation assays. Moreover, the overexpression of TAZ inhibited RANKL-induced osteoclast formation, whereas silencing of TAZ reduced it. Mechanistically, TAZ bound to TGF-activated kinase 1 (TAK1) and reciprocally inhibited NF-κB signaling, suppressing osteoclast differentiation. Collectively, our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.
Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone
Authors: ten Hoorn Sanne , Sommeijer Dirkje W. , Elliott Faye , Fisher David , de Back Tim R. , Trinh Anne , Koens Lianne , Maughan Tim , Seligmann Jenny , Seymour Matthew T. , Quirke Phil , Adams Richard , Richman Susan D. , Punt Cornelis J. A. , Vermeulen Louis
Published: July 2021

Background

Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.

Methods

Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.

Results

When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034).

Conclusions

The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.
Tissue-specific 5-hydroxymethylcytosine landscape of the human genome
Authors: He Bo , Zhang Chao , Zhang Xiaoxue , Fan Yu , Zeng Hu , Liu Jun’e , Meng Haowei , Bai Dongsheng , Peng Jinying , Zhang Qian , Tao Wei , Yi Chengqi
Published: July 2021

5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions.
The Welwitschia genome reveals a unique biology underpinning extreme longevity in deserts
Authors: Wan Tao , Liu Zhiming , Leitch Ilia J. , Xin Haiping , Maggs-Kölling Gillian , Gong Yanbing , Li Zhen , Marais Eugene , Liao Yiying , Dai Can , Liu Fan , Wu Qijia , Song Chi , Zhou Yadong , Huang Weichang , Jiang Kai , Wang Qi , Yang Yong , Zhong Zhixiang , Yang Ming , Yan Xue , Hu Guangwan , Hou Chen , Su Yingjuan , Feng Shixiu , Yang Ji , Yan Jijun , Chu Jinfang , Chen Fan , Ran Jinhua , Wang Xiaoquan , Van de Peer Yves , Leitch Andrew R. , Wang Qingfeng
Published: July 2021

The gymnosperm Welwitschia mirabilis belongs to the ancient, enigmatic gnetophyte lineage. It is a unique desert plant with extreme longevity and two ever-elongating leaves. We present a chromosome-level assembly of its genome (6.8 Gb/1 C) together with methylome and transcriptome data to explore its astonishing biology. We also present a refined, high-quality assembly of Gnetum montanum to enhance our understanding of gnetophyte genome evolution. The Welwitschia genome has been shaped by a lineage-specific ancient, whole genome duplication (~86 million years ago) and more recently (1-2 million years) by bursts of retrotransposon activity. High levels of cytosine methylation (particularly at CHH motifs) are associated with retrotransposons, whilst long-term deamination has resulted in an exceptionally GC-poor genome. Changes in copy number and/or expression of gene families and transcription factors (e.g. R2R3MYB, SAUR) controlling cell growth, differentiation and metabolism underpin the plant’s longevity and tolerance to temperature, nutrient and water stress.
Energy efficiency and biological interactions define the core microbiome of deep oligotrophic groundwater
Authors: Mehrshad Maliheh , Lopez-Fernandez Margarita , Sundh John , Bell Emma , Simone Domenico , Buck Moritz , Bernier-Latmani Rizlan , Bertilsson Stefan , Dopson Mark
Published: July 2021

While oligotrophic deep groundwaters host active microbes attuned to the low-end of the bioenergetics spectrum, the ecological constraints on microbial niches in these ecosystems and their consequences for microbiome convergence are unknown. Here, we provide a genome-resolved, integrated omics analysis comparing archaeal and bacterial communities in disconnected fracture fluids of the Fennoscandian Shield in Europe. Leveraging a dataset that combines metagenomes, single cell genomes, and metatranscriptomes, we show that groundwaters flowing in similar lithologies offer fixed niches that are occupied by a common core microbiome. Functional expression analysis highlights that these deep groundwater ecosystems foster diverse, yet cooperative communities adapted to this setting. We suggest that these communities stimulate cooperation by expression of functions related to ecological traits, such as aggregate or biofilm formation, while alleviating the burden on microorganisms producing compounds or functions that provide a collective benefit by facilitating reciprocal promiscuous metabolic partnerships with other members of the community. We hypothesize that an episodic lifestyle enabled by reversible bacteriostatic functions ensures the subsistence of the oligotrophic deep groundwater microbiome.
Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration
Authors: Clapes Thomas , Polyzou Aikaterini , Prater Pia , Sagar  , Morales-Hernández Antonio , Ferrarini Mariana Galvao , Kehrer Natalie , Lefkopoulos Stylianos , Bergo Veronica , Hummel Barbara , Obier Nadine , Maticzka Daniel , Bridgeman Anne , Herman Josip S. , Ilik Ibrahim , Klaeylé Lhéanna , Rehwinkel Jan , McKinney-Freeman Shannon , Backofen Rolf , Akhtar Asifa , Cabezas-Wallscheid Nina , Sawarkar Ritwick , Rebollo Rita , Grün Dominic , Trompouki Eirini
Published: July 2021

Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5−/− HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence.
Protein engineering of the aldoxime dehydratase from Bacillus sp. OxB-1 based on a rational sequence alignment approach
Authors: Oike Keiko , Sproß Jens , Matsui Daisuke , Asano Yasuhisa , Gröger Harald
Published: July 2021

Recently, the program INTMSAlign_HiSol for identifying aggregation hotspots in proteins only requiring secondary structure data was introduced. We explored the utility of this program further and applied it for engineering of the aldoxime dehydratase from Bacillus sp. OxB-1. Towards this end, the effect of inverting the hydropathy at selected positions of the amino acid sequence on the enzymatic activity was studied leading to 60% of our constructed variants, which showed improved activity. In part, this activity increase can be rationalised by an improved heme incorporation of the variants. For example, a single mutation gave a 1.8 fold increased enzymatic activity and 30% improved absolute heme incorporation.
Quantum inspired community detection for analysis of biodiversity change driven by land-use conversion and climate change
Authors: Akbar Sana , Saritha Sri Khetwat
Published: July 2021

Community detection remains little explored in the analysis of biodiversity change. The challenges linked with global biodiversity change have also multiplied manifold in the past few decades. Moreover, most studies concerning biodiversity change lack the quantitative treatment central to species distribution modeling. Empirical analysis of species distribution and abundance is thus integral to the study of biodiversity loss and biodiversity alterations. Community detection is therefore expected to efficiently model the topological aspect of biodiversity change driven by land-use conversion and climate change; given that it has already proven superior for diverse problems in the domain of social network analysis and subgroup discovery in complex systems. Thus, quantum inspired community detection is proposed as a novel technique to predict biodiversity change considering tiger population in eighteen states of India; leading to benchmarking of two novel datasets. Elements of land-use conversion and climate change are explored to design these datasets viz.—Landscape based distribution and Number of tiger reserves based distribution respectively; for predicting regions expected to maximize Tiger population growth. Furthermore, validation of the proposed framework on the said datasets is performed using standard community detection metrics like—Modularity, Normalized Mutual Information (NMI), Adjusted Rand Index (ARI), Degree distribution, Degree centrality and Edge-betweenness centrality. Quantum inspired community detection has also been successful in demonstrating an association between biodiversity change, land-use conversion and climate change; validated statistically by Pearson’s correlation coefficient andpvalue test. Finally, modularity distribution based on parameter tuning establishes the superiority of the second dataset based on the number of Tiger reserves—in predicting regions maximizing Tiger population growth fostering species distribution and abundance; apart from scripting a stronger correlation of biodiversity change with land-use conversion.
Stage-dependent choriocapillaris impairment in Best vitelliform macular dystrophy characterized by optical coherence tomography angiography
Authors: Jauregui Ruben , Parmann Rait , Nuzbrokh Yan , Tsang Stephen H. , Sparrow Janet R.
Published: July 2021

Characterization of vascular impairment in Best vitelliform macular dystrophy (BVMD) is essential for the development of treatment modalities and therapy trials. As such, we seek to characterize the choriocapillaris (CC) at each stage of the disease process in 22 patients (44 eyes) with a diagnosis of BVMD confirmed by genetic sequencing. We utilize optical coherence tomography angiography (OCTA) images to characterize the CC and correlate our findings to the status of the retinal pigment epithelium (RPE) as observed on short-wavelength fundus autofluorescence (SW-AF) images. We observed that in the vitelliruptive stage, the CC appeared as bright and granular in the area where the vitelliform lesion was present. In the atrophic stage, varying degrees of CC atrophy were observed within the lesion area, with the regions of CC atrophy appearing as hypoautofluorescent on SW-AF images. Our results suggest that the CC impairment observed in the vitelliruptive stage of BVMD progressively culminates in the CC atrophy observed at the atrophic stage. As such, OCTA imaging can be used to characterize CC impairment in BVMD patients as part of diagnosis and tracking of disease progression. Our findings suggest that the best window of opportunity for therapeutic approaches is before the atrophic stage, as it is during this stage that CC atrophy is observed.
Uptake and release characteristics of serotonin hydrochloride by natural Cuban zeolite containing clinoptilolite and mordenite
Authors: Grass Jan-Paul , Pals Ulrike , Inayat Alexandra , Schwieger Wilhelm , Hartmann Martin , Dathe Wilfried
Published: July 2021

Serotonin (5-HT) plays an important role in human physiology. An excess of this native regulator within the human gut can be partially controlled by orally consuming zeolite. Therefore, this study focuses on the kinetics of the uptake and release of serotonin hydrochloride (5-HT-hc) by natural Cuban zeolite containing clinoptilolite and mordenite at different pH levels using UV–Vis spectroscopy. 5-HT-hc is stable under the following investigated experimental conditions: incubation temperature of 36 °C; and at a pH of 5, 7, and 9. Independent of the zeolite framework, the 5-HT-hc is adsorbed without changing its molecular structure. The uptake and release of 5-HT-hc were not correlated to the textural properties of these aluminosilicates. The investigated zeolites adsorbed 5-HT-hc at about 14 mg per gram zeolite with no large differences observed between different samples. Release studies of 5-HT-hc-loaded zeolite revealed that the 5-HT-hc is strongly bound to the zeolite, and independent of the pH value and zeolite framework only up to 12.7% was released into the water.
Effects of illuminance and correlated color temperature of indoor light on emotion perception
Authors: Li Yun , Ru Taotao , Chen Qingwei , Qian Liu , Luo Xianghang , Zhou Guofu
Published: July 2021

The acute non-image forming (NIF) effects of daytime light on momentary mood had been-although not always-established in the current literature. It still remains largely unknown whether short-time light exposure would modulate emotion perception in healthy adults. The current study (N = 48) was conducted to explore the effects of illuminance (100 lx vs. 1000 lx at eye level) and correlated color temperature (CCT, 2700 K vs. 6500 K) on explicit and implicit emotion perception that was assessed with emotional face judgment task and emotional oddball task respectively. Results showed that lower CCT significantly decreased negative response bias in the face judgment task, with labeling ambiguous faces less fearful under 2700 K vs. 6500 K condition. Moreover, participants responded slightly faster for emotional pictures under 6500 K vs. 2700 K condition, but no significant effect of illuminance or CCT on negativity bias was revealed in the emotional oddball task. These findings highlighted the differential role of illuminance and CCT in regulating instant emotion perception and suggested a task-dependent moderation of light spectrum on negativity bias.
Analyses of Gnai3-iresGFP reporter mice reveal unknown Gαi3 expression sites
Authors: Leiss Veronika , Reisinger Ellen , Speidel Annika , Beer-Hammer Sandra , Nürnberg Bernd
Published: July 2021

Inhibitory G proteins (Giproteins) are highly homologous but play distinct biological roles. However, their isoform-specific detection remains challenging. To facilitate the analysis of Gαi3expression, we generated aGnai3﻿﻿-﻿iresGFP reporter mouse line. An internal ribosomal entry site (IRES) was inserted behind the stop-codon of theGnai3gene to initiate simultaneous translation of the GFP cDNA together with Gαi3. The expression of GFP was confirmed in spleen and thymus tissue by immunoblot analysis. Importantly, the GFP knock-in (ki) did not alter Gαi3expression levels in all organs tested including spleen and thymus compared to wild-type littermates. Flow cytometry of thymocytes, splenic and blood cell suspensions revealed significantly higher GFP fluorescence intensities in homozygous ki/ki animals compared to heterozygous mice (+/ki). Using cell-type specific surface markers GFP fluorescence was assigned to B cells, T cells, macrophages and granulocytes from both splenic and blood cells and additionally blood-derived platelets. Moreover, immunofluorescent staining of the inner ear from knock-in mice unraveled GFP expression in sensory and non-sensory cell types, with highest levels in Deiter’s cells and in the first row of Hensen’s cells in the organ of Corti, indicating a novel site for Gαi3expression. In summary, theGnai3-﻿﻿iresGFP reporter mouse represents an ideal tool for precise analyses of Gαi3expression patterns and sites.
Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography
Authors: Park Jang Ryul , Lee ByungKun , Lee Min Ji , Kim Kyuseok , Oh Wang-Yuhl
Published: July 2021

We developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.
Emergent topological fields and relativistic phonons within the thermoelectricity in topological insulators
Authors: Faílde Daniel , Baldomir Daniel
Published: July 2021

Topological edge states are predicted to be responsible for the high efficient thermoelectric response of topological insulators, currently the best thermoelectric materials. However, to explain their figure of merit the coexistence of topological electrons, entropy and phonons can not be considered independently. In a background that puts together electrodynamics and topology, through an expression for the topological intrinsic field, we treat relativistic phonons within the topological surface showing their ability to modulate the Berry curvature of the bands and then playing a fundamental role in the thermoelectric effect. Finally, we show how the topological insulators under such relativistic thermal excitations keep time reversal symmetry allowing the observation of high figures of merit at high temperatures. The emergence of this new intrinsic topological field and other constraints are suitable to have experimental consequences opening new possibilities of improving the efficiency of this topological effect for their based technology.
Untargeted metabolomics analysis of Ralstonia eutropha during plant oil cultivations reveals the presence of a fucose salvage pathway
Authors: Gutschmann Björn , Bock Martina C. E. , Jahns Stefan , Neubauer Peter , Brigham Christopher J. , Riedel Sebastian L.
Published: July 2021

Process engineering of biotechnological productions can benefit greatly from comprehensive analysis of microbial physiology and metabolism. Ralstonia eutropha (syn. Cupriavidus necator) is one of the best studied organisms for the synthesis of biodegradable polyhydroxyalkanoate (PHA). A comprehensive metabolomic study during bioreactor cultivations with the wild-type (H16) and an engineered (Re2058/pCB113) R. eutropha strain for short- and or medium-chain-length PHA synthesis has been carried out. PHA production from plant oil was triggered through nitrogen limitation. Sample quenching allowed to conserve the metabolic states of the cells for subsequent untargeted metabolomic analysis, which consisted of GC–MS and LC–MS analysis. Multivariate data analysis resulted in identification of significant changes in concentrations of oxidative stress-related metabolites and a subsequent accumulation of antioxidative compounds. Moreover, metabolites involved in the de novo synthesis of GDP-l-fucose as well as the fucose salvage pathway were identified. The related formation of fucose-containing exopolysaccharides potentially supports the emulsion-based growth of R. eutropha on plant oils.
PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer
Authors: Xun Guangsu , Hu Wei , Li Bing
Published: July 2021

Among all cancer types, lung cancer has already become the leading cause of cancer-related death around the world. The molecular mechanism understanding this development is still needed to be improved to treat lung cancer. Stathmin (STMN1) was initially identified as a cytoplasmic protein phosphorylated responding to cell signal and controlled cell physiological processes. The dysregulation of STMN1 is found in various kinds of tumors. However, the molecular mechanism of STMN1 regulating lung cancer is still unclear. Here, we found that STMN1 was overexpressed in lung cancer tissues and associated with worse survival rates of lung cancer patients. Inhibition of STMN1 suppressed lung cancer cell growth, migration and invasion, and promoted drug sensitivity. Moreover, PTEN loss promoted STMN1 expression via PI3K/AKT pathway. PTEN loss ameliorated the inhibition of cell growth, migration and invasion, and drug sensitivity induced by STMN1 knockdown in lung cancer. The high expression of STMN1 was negatively correlated with the low expression of PTEN in lung cancer specimens. Overall, our work demonstrated that PTEN regulated the oncogenic function of STMN1 in lung cancer.
Immune checkpoint blockade in triple negative breast cancer influenced by B cells through myeloid-derived suppressor cells
Authors: Vito Alyssa , Salem Omar , El-Sayes Nader , MacFawn Ian P. , Portillo Ana L. , Milne Katy , Harrington Danielle , Ashkar Ali A. , Wan Yonghong , Workenhe Samuel T. , Nelson Brad H. , Bruno Tullia C. , Mossman Karen L.
Published: July 2021

Triple negative breast cancer holds a dismal clinical outcome and as such, patients routinely undergo aggressive, highly toxic treatment regimens. Clinical trials for TNBC employing immune checkpoint blockade in combination with chemotherapy show modest prognostic benefit, but the percentage of patients that respond to treatment is low, and patients often succumb to relapsed disease. Here, we show that a combination immunotherapy platform utilizing low dose chemotherapy (FEC) combined with oncolytic virotherapy (oHSV-1) increases tumor-infiltrating lymphocytes, in otherwise immune-bare tumors, allowing 60% of mice to achieve durable tumor regression when treated with immune checkpoint blockade. Whole-tumor RNA sequencing of mice treated with FEC + oHSV-1 shows an upregulation of B cell receptor signaling pathways and depletion of B cells prior to the start of treatment in mice results in complete loss of therapeutic efficacy and expansion of myeloid-derived suppressor cells. Additionally, RNA sequencing data shows that FEC + oHSV-1 suppresses genes associated with myeloid-derived suppressor cells, a key population of cells that drive immune escape and mediate therapeutic resistance. These findings highlight the importance of tumor-infiltrating B cells as drivers of antitumor immunity and their potential role in the regulation of myeloid-derived suppressor cells.
Anomalous and normal dislocation modes in Floquet topological insulators
Authors: Nag Tanay , Roy Bitan
Published: July 2021

Electronic bands featuring nontrivial bulk topological invariant manifest through robust gapless modes at the boundaries, e.g., edges and surfaces. As such this bulk-boundary correspondence is also operative in driven quantum materials. For example, a suitable periodic drive can convert a trivial insulator into a Floquet topological insulator (FTI) that accommodates nondissipative dynamic gapless modes at the interfaces with vacuum. Here we theoretically demonstrate that dislocations, ubiquitous lattice defects in crystals, can probe FTIs as well as unconventional π-trivial insulator in the bulk of driven quantum systems by supporting normal and anomalous modes, localized near the defect core. Respectively, normal and anomalous dislocation modes reside at the Floquet zone center and boundaries. We exemplify these outcomes specifically for two-dimensional (2D) Floquet Chern insulator and px + ipy superconductor, where the dislocation modes are respectively constituted by charged and neutral Majorana fermions. Our findings should be, therefore, instrumental in probing Floquet topological phases in the state-of-the-art experiments in driven quantum crystals, cold atomic setups, and photonic and phononic metamaterials through bulk topological lattice defects.
Dinophyceae can use exudates as weapons against the parasite Amoebophrya sp. (Syndiniales)
Authors: Long Marc , Marie Dominique , Szymczak Jeremy , Toullec Jordan , Bigeard Estelle , Sourisseau Marc , Le Gac Mickael , Guillou Laure , Jauzein Cécile
Published: July 2021

Parasites in the genus Amoebophrya sp. infest dinoflagellate hosts in marine ecosystems and can be determining factors in the demise of blooms, including toxic red tides. These parasitic protists, however, rarely cause the total collapse of Dinophyceae blooms. Experimental addition of parasite-resistant Dinophyceae (Alexandrium minutum or Scrippsiella donghaienis) or exudates into a well-established host-parasite coculture (Scrippsiella acuminata-Amoebophrya sp.) mitigated parasite success and increased the survival of the sensitive host. This effect was mediated by waterborne molecules without the need for a physical contact. The strength of the parasite defenses varied between dinoflagellate species, and strains of A. minutum and was enhanced with increasing resistant host cell concentrations. The addition of resistant strains or exudates never prevented the parasite transmission entirely. Survival time of Amoebophrya sp. free-living stages (dinospores) decreased in presence of A. minutum but not of S. donghaienis. Parasite progeny drastically decreased with both species. Integrity of the dinospore membrane was altered by A. minutum, providing a first indication on the mode of action of anti-parasitic molecules. These results demonstrate that extracellular defenses can be an effective strategy against parasites that protects not only the resistant cells producing them, but also the surrounding community.
A three-dimensional hydrogel-modified indium tin oxide electrode with enhanced performance for in situ electrochemical detection of extracellular H2O2
Authors: Zhou Shiying , Wang Xianfeng , Jiang Liuyi , Sun Human , Huo Danqun , Hou Changjun
Published: July 2021

Two novel sensors (Hemin-G4/Au/GCE and Hemin-G4/Au/ITO) were developed for sensitive detection of extracellular H2O2, in which the Hemin-G4/Au/ITO as a self-supporting electrode can grow cells to achieve in situ detection.
Empirical determination of explosive vapor transport efficiencies
Authors: Mullen Matthew , Katilie Christopher , Collins Greg E. , Giordano Braden C.
Published: July 2021

Fluorinated ethylene propylene is identified as a superior tubing substrate for transport of explosive vapors including RDX at relatively low temperatures (30 °C).
Inexpensive ion-selective electrodes for the simultaneous monitoring of potassium and nitrate concentrations in nutrient solutions
Authors: Miras Marina , García María Soledad , Martínez Vicente , Ortuño Joaquín Ángel
Published: July 2021

A fast, simple and inexpensive potentiometric method has been developed for the determination of potassium and nitrate in nutrient solutions, by means of ion-selective electrodes based on plasticized PVC membranes containing an ion-exchanger.
Synthesis and chemical stability of technetium nitrides
Authors: Siska Emily , Smith Dean , Salamat Ashkan , Lawler Keith V. , Lavina Barbara , Poineau Frederic , Forster Paul M.
Published: July 2021

We demonstrate the synthesis and phase stability of TcN, Tc2N, and a substoichiometric TcNx from 0 to 50 GPa and to 2500 K in a laser-heated diamond anvil cell.
Facile protein conjugation of platinum for light-activated cytotoxic payload release
Authors: Imberti Cinzia , Lermyte Frederik , Friar Emily P. , O'Connor Peter B. , Sadler Peter J.
Published: July 2021

This platinum anticancer complex can be conjugated to proteins, including antibodies, under mild conditions and activated by visible light, providing a basis for highly selective cancer phototherapy.
A new compound Pt3Bi2S2 with superior performance for the hydrogen evolution reaction
Authors: Fang Yuqiang , Wang Sishun , Lin Gaoxin , Wang Xin , Huang Fuqiang
Published: July 2021

A new compound Pt3Bi2S2 exhibits excellent hydrogen evolution performance and long-term stability, which is higher than that of Pt/C.
Cross β amyloid assemblies as complex catalytic machinery
Authors: Pal Sumit , Goswami Surashree , Das Dibyendu
Published: July 2021

Short peptide-based cross β amyloid assemblies can mimic advanced enzyme functions and possibly were the earliest protein folds.