bluuebunny/crossref_metadata_2025 huggingface dataset:
An open source plant kinase chemogenomics set
Authors: Ercoli Maria Florencia , Ramos Priscila Zonzini , Jain Rashmi , Pilotte Joseph , Dong Oliver Xiaoou , Thompson Ty , Wells Carrow I. , Elkins Jonathan M. , Edwards Aled M. , Couñago Rafael M. , Drewry David H. , Ronald Pamela C.
Published: November 2022

One hundred twenty‐nine protein kinases, selected to represent the diversity of the rice (Oryza sativa) kinome, were cloned and tested for expression in Escherichia coli. Forty of these rice kinases were purified and screened using differential scanning fluorimetry (DSF) against 627 diverse kinase inhibitors, with a range of structures and activities targeting diverse human kinases. Thirty‐seven active compounds were then tested for their ability to modify primary root development in Arabidopsis. Of these, 14 compounds caused a significant reduction of primary root length compared with control plants. Two of these inhibitory compounds bind to the predicted orthologue of Arabidopsis PSKR1, one of two receptors for PSK, a small sulfated peptide that positively controls root development. The reduced root length phenotype could not be rescued by the exogenous addition of the PSK peptide, suggesting that chemical treatment may inhibit both PSKR1 and its closely related receptor PSKR2. Six of the compounds acting as root growth inhibitors in Arabidopsis conferred the same effect in rice. Compound RAF265 (CHIR‐265), previously shown to bind the human kinase BRAF (B‐Raf proto‐oncogene, serine/threonine kinase), also binds to nine highly conserved rice kinases tested. The binding of human and rice kinases to the same compound suggests that human kinase inhibitor sets will be useful for dissecting the function of plant kinases.
Delineating gene–environment effects using virtual twins of patients treated with clozapine
Authors: Mostafa Sam , Polasek Thomas M. , Bousman Chad , Rostami‐Hodjegan Amin , Sheffield Leslie J. , Everall Ian , Pantelis Christos , Kirkpatrick Carl M. J.
Published: November 2022

Studies that focus on individual covariates, while ignoring their interactions, may not be adequate for model‐informed precision dosing (MIPD) in any given patient. Genetic variations that influence protein synthesis should be studied in conjunction with environmental covariates, such as cigarette smoking. The aim of this study was to build virtual twins (VTs) of real patients receiving clozapine with interacting covariates related to genetics and environment and to delineate the impact of interacting covariates on predicted clozapine plasma concentrations. Clozapine‐treated patients with schizophrenia (N = 42) with observed clozapine plasma concentrations, demographic, environmental, and genotype data were used to construct VTs in Simcyp. The effect of increased covariate virtualization was assessed by performing simulations under three conditions: “low” (demographic), “medium” (demographic and environmental interaction), and “high” (demographic and environmental/genotype interaction) covariate virtualization. Increasing covariate virtualization with interaction improved the coefficient of variation (R2) from 0.07 in the low model to 0.391 and 0.368 in the medium and high models, respectively. Whereas R2 was similar between the medium and high models, the high covariate virtualization model had improved accuracy, with systematic bias of predicted clozapine plasma concentration improving from −138.48 ng/ml to −74.65 ng/ml. A high level of covariate virtualization (demographic, environmental, and genotype) may be required for MIPD using VTs.
Suppression of Impact Ionization by Carbon Doping in the GaN Buffer Layer in InAlN/GaN‐Based High Electron Mobility Transistors
Authors: Sarkar Sujan , Khade Ramdas P. , DasGupta Nandita , DasGupta Amitava
Published: November 2022

Herein, the impact ionization in InAlN/GaN‐based high electron mobility transistors (HEMTs) is studied for the first time. It is shown that the carbon doping in the GaN buffer layer can suppress impact ionization by reducing the electric field at the drain side gate edge. For comparison, two wafers are taken. In one wafer (D1), the GaN buffer layer is unintentionally doped, and in another wafer (D2), the buffer layer is carbon doped with a doping concentration of at a distance of 500 nm from the InAlN–GaN interface. The impact ionization is probed from the bell‐shaped nature of theIG – VGScharacteristics. The bell‐shaped nature is observed in D1 for the drain‐to‐source voltage (VDS) 6 V, whereas it is absent in D2. Floating source measurements confirm the occurrence of impact ionization in D1. At a lower temperature (−60 °C), the impact ionization rate of D1 increases even though there is no sign of impact ionization in D2. A technology computer‐aided design simulation shows that the peak electric field at the drain side gate edge of D2 is lower than that of D1.
Exploring the mechanism of action of Chinese medicine in regulating liver fibrosis based on the alteration of glucose metabolic pathways
Authors: Guo Xinhua , Zheng Bowen , Wang Jiahui , Zhao Tiejian , Zheng Yang
Published: November 2022

In recent years, metabolic reprogramming in liver fibrosis has become a research hotspot in the field of liver fibrosis at home and abroad. Liver fibrosis is a pathological change caused by chronic liver injury from a variety of causes. Liver fibrosis is a common pathological feature of many chronic liver diseases such as chronic hepatitis B, non‐alcoholic steatohepatitis, and autoimmune hepatitis, as well as the pathogenesis of the disease. The development of chronic liver disease into cirrhosis must go through the pathological process of liver fibrosis, in which hepatic stellate cells (HSC) play an important role. Following liver injury, HSC are activated and transdifferentiated into scar‐forming myofibroblasts, which drive the trauma healing response and which rely on the deposition of collagen‐rich extracellular matrix to maintain tissue integrity. This reaction will continue without strict control, which will lead to excessive accumulation of matrix and liver fibrosis. The mechanisms and clinical studies of liver fibrosis have been the focus of research in liver diseases. In recent years, several studies have revealed the mechanism of HSC metabolic reprogramming and the impact of this process on liver fibrosis, in which glucose metabolic reprogramming plays an important role in the activation of HSC, and it mainly meets the energy demand of HSC activation by upregulating glycolysis. Glycolysis is the process by which one molecule of glucose is broken down into two molecules of pyruvate and produces energy and lactate under anaerobic conditions. Various factors have been found to be involved in regulating the glycolytic process of HSC, including glucose transport, intracellular processing of glucose, exosome secretion, and lactate production, etc. Inhibition of the glycolytic process of HSC can be an effective strategy against liver fibrosis. Currently, the combined action of multiple targets and links of Chinese medicine such as turmeric, comfrey, rhubarb and scutellaria baicalensis against the mechanism of liver fibrosis can effectively improve or even reverse liver fibrosis. This paper summarizes that turmeric extract curcumin, comfrey extract comfreyin, rhubarb, Subtle yang yu yin granules, Scutellaria baicalensis extract oroxylin A and cardamom extract cardamomin affect liver fibrosis by regulating gluconeogenic reprogramming. Therefore, studying the mechanism of action of TCM in regulating liver fibrosis through reprogramming of glucose metabolism is promising to explore new methods and approaches for Chinese Medicine modernization research.
Synthesis and characterization of molecularly imprinted polymers for detection of the local anesthetic lidocaine in urine
Authors: Takahashi Fumiki , Matsuda Kazusane , Nakazawa Tomoyuki , Mori Shuki , Yoshida Masachika , Shimizu Ryo , Tatsumi Hirosuke , Jin Jiye
Published: November 2022

Molecularly imprinted polymers are materials that can capture target analytes using molecular recognition. These polymers can efficiently detect trace target chemical species in biological samples, such as urine and blood, containing various matrix components. We aimed to analyze the interaction of molecularly imprinted polymers with the target molecule lidocaine, which is an amino amide pharmaceutical. Lidocaine‐templated molecularly imprinted polymers were synthesized by bulk polymerization. Gas chromatography‐mass spectrometry showed there was a strong interaction between lidocaine and the recognition site in the molecularly imprinted polymers. Non‐selective adsorption of lidocaine on the molecularly imprinted polymers was confirmed and characterized by Scatchard analysis. The washing solution was optimized for the separation of lidocaine from the structurally similar anesthetics procaine and tetracaine by taking advantage of differences in binding strength. The molecularly imprinted polymers could adsorb lidocaine in urine samples and were not affected by interfering compounds. Consequently, they could be applied to the analysis of biological materials. These results suggest that the molecularly imprinted polymers can be used for separation and detection with high selectivity and could be applied in forensic and clinical analysis.
WIMP and FIMP dark matter in singlet-triplet fermionic model
Authors: Bélanger Geneviève , Choubey Sandhya , Godbole Rohini M. , Khan Sarif , Mitra Manimala , Roy Abhishek
Published: November 2022

Abstract

We present an extension of the SM involving three triplet fermions, one triplet scalar and one singlet fermion, which can explain both neutrino masses and dark matter. One triplet of fermions and the singlet are odd under a Z2 symmetry, thus the model features two possible dark matter candidates. The two remaining Z2-even triplet fermions can reproduce the neutrino masses and oscillation parameters consistent with observations. We consider the case where the singlet has feeble couplings while the triplet is weakly interacting and investigate the different possibilities for reproducing the observed dark matter relic density. This includes production of the triplet WIMP from freeze-out and from decay of the singlet as well as freeze-in production of the singlet from decay of particles that belong to the thermal bath or are thermally decoupled. While freeze-in production is usually dominated by decay processes, we also show cases where the annihilation of bath particles give substantial contribution to the final relic density. This occurs when the new scalars are below the TeV scale, thus in the reach of the LHC. The next-to-lightest odd particle can be long-lived and can alter the successful BBN predictions for the abundance of light elements, these constraints are relevant in both the scenarios where the singlet or the triplet are the long-lived particle. In the case where the triplet is the DM, the model is subject to constraints from ongoing direct, indirect and collider experiments. When the singlet is the DM, the triplet which is the next-to-lightest odd particle can be long-lived and can be probed at the proposed MATHUSLA detector. Finally we also address the detection prospects of triplet fermions and scalars at the LHC.
Emergent de Sitter cosmology near black hole horizon
Authors: Rasulian Ida M.
Published: November 2022

Abstract

We propose an effective model for an exponentially expanding universe in the brane-world scenario. The setup consists of a 5D black hole and a brane close to the black hole horizon. In case the brane acquires a specific configuration, which we deduce from stability arguments, the induced metric outside the black hole horizon on the brane becomes de Sitter in static coordinates. Studying the Einstein equations perturbatively we find the effective gravity on the brane at this level and derive the 4D gravitational constant. Considering a homogeneous and isotropic fluid in the corresponding FLRW coordinates we find that the bulk fluid density inside the brane, which has the same equation of state as the fluid on the brane, contributes to the energy density in the Friedmann equation and therefore in late time may be attributed to dark matter. Studying the stability of the setup we observe that the brane becomes stabilized, in the presence of matter on the brane, with a de Sitter length that is qualitatively of the order of Schwarzschild radius of the universe due to matter. We briefly discuss effects that can bound the de Sitter lifetime. In particular this model can provide a lifetime compatible with Trans-Planckian Censorship conjecture for the current de Sitter phase.
ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response
Authors: Sule Amrita , Golding Sarah E. , Ahmad Syed F. , Watson James , Ahmed Mostafa H. , Kellogg Glen E. , Bernas Tytus , Koebley Sean , Reed Jason C. , Povirk Lawrence F. , Valerie Kristoffer
Published: November 2022

Ataxia telangiectasia mutated (ATM) is a serine–threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65–S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM–PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear–cytoplasmic shuttling mediated by the nuclear export receptor CRM1.
Changes in the moisture contribution over global arid regions
Authors: Wang Chenghai , Li Jiamin , Zhang Feimin , Yang Kai
Published: November 2022

Arid regions have deficient precipitation, understanding the sources and transportation of moisture for precipitation are crucial. This study examined the major moisture contributions for global six arid regions, which are classified as inland arid region (China-Mongolia) and coastal arid regions (North Africa, West Asia, West United States, South Africa, South Africa and Australia). Results indicated that, the moisture for precipitation in coastal arid regions originates mostly from the ocean, which is influenced by the general circulation, particularly by the sinking branch of the Hadley cell. For inland arid region (China–Mongolia), the surrounding mountains supply more than 150 mm of moisture in wet months due to the ablation of glacial and snow melting. In arid regions, the moisture for precipitation is mostly contributed by advection of large-scale circulation, while the contribution of local moisture recycling is secondary. The moisture available for precipitation in wet and dry months depends on the general circulation. Moisture transportation in wet months is 10 times more than that in dry months, and the moisture sources differ greatly in wet and dry months. In both wet and dry months, the external moisture transported into arid regions has significantly decreasing trend during the period 1990–2019. The decreasing trend of precipitation recycling ratio in arid regions are greater than that in the globe. The decreased precipitation and moisture in arid regions suggest a potential drying trend.
Effect of time of diagnosis to surgery on outcome, including long-term neurodevelopmental outcome, in necrotizing enterocolitis
Authors: Duric Bea , Gray Cecilia , Alexander Allen , Naik Shivani , Haffenden Verity , Yardley Iain
Published: November 2022

A systematic review of the PubMed and EMBASE databases was carried out to determine if time from diagnosis to surgery affects outcomes in necrotising enterocolitis. The study was registered on the PROSPERO website. Studies reporting both time to surgery and at least one clinical outcome measure in infants undergoing surgery for NEC were included. The initial search returned 1121 articles. After removing duplicates, title, and abstract screening, 49 remained for full-text review. Of these, only two reported both timing of surgery for NEC and at least one clinical outcome. The total number of neonates included was 202. Outcomes reported were death and/or parenteral nutrition use 28 days post surgery in one study and white matter brain injury in the other. No statistically significant association was found between any of the outcomes reported and timing of surgery. There were, however, significant differences associated with non-modifiable risk factors, such as age and gestation, at presentation. However, very few studies report this as a variable. Given the continuing poor outcomes and heterogeneous nature of NEC and its treatments, further large-scale prospective studies are required to examine the impact of timing of surgery, alongside other, potentially modifiable factors on outcome in NEC.
Maternal anxiety forecasts shorter prolongation of pregnancies complicated by early-onset preeclampsia
Authors: van Esch Joris J. A. , Bolte Antoinette C. , Spaanderman Marc E. A. , Vandenbussche Frank P. H. A. , de Weerth Carolina , Beijers Roseriet
Published: November 2022

Purpose

In early-onset preeclampsia, each additional day of pregnancy prolongation reduces offspring infant mortality about 9%. We evaluated if maternal stress at admission to hospital for early-onset preeclampsia predicted admission-to-delivery intervals in days.

Methods

This prospective, longitudinal cohort-study involved 15 singleton pregnancies with a diagnosis of preeclampsia before 34 weeks gestation with intended expectant management. Upon hospital admission, maternal psychological stress was assessed with questionnaires and physiological stress with hair cortisol. Hair samples were analyzed in three hair segments representing the preconception period, and the first and second trimester of pregnancy.

Results

Mean pregnancy prolongation was 16.2 days. Higher maternal anxiety at hospital admission significantly correlated with shorter admission-to-delivery intervals (r = − 0.54, p = 0.04). Chronically increased hair cortisol concentrations (i.e. from preconception through the second trimester) of pregnancy tended to be related to shorter admission-to-delivery intervals (p <. 10).

Conclusion

Higher reported anxiety is, and chronically high hair cortisol tended to be, related with fewer days of prolongation from admission to delivery in women with early-onset preeclampsia. These findings suggest that maternal stress might be a potential determinant of disease progression. Future research into early innovative stress-reducing interventions for early-onset preeclampsia may shed more light on the etiology and treatment of this disease.
Present and future of the diagnostic work-up of multiple sclerosis: the imaging perspective
Authors: Filippi Massimo , Preziosa Paolo , Arnold Douglas L. , Barkhof Frederik , Harrison Daniel M. , Maggi Pietro , Mainero Caterina , Montalban Xavier , Sechi Elia , Weinshenker Brian G. , Rocca Maria A.
Published: November 2022

In recent years, the use of magnetic resonance imaging (MRI) for the diagnostic work-up of multiple sclerosis (MS) has evolved considerably. The 2017 McDonald criteria show high sensitivity and accuracy in predicting a second clinical attack in patients with a typical clinically isolated syndrome and allow an earlier diagnosis of MS. They have been validated, are evidence-based, simplify the clinical use of MRI criteria and improve MS patients’ management. However, to limit the risk of misdiagnosis, they should be applied by expert clinicians only after the careful exclusion of alternative diagnoses. Recently, new MRI markers have been proposed to improve diagnostic specificity for MS and reduce the risk of misdiagnosis. The central vein sign and chronic active lesions (i.e., paramagnetic rim lesions) may increase the specificity of MS diagnostic criteria, but further effort is necessary to validate and standardize their assessment before implementing them in the clinical setting. The feasibility of subpial demyelination assessment and the clinical relevance of leptomeningeal enhancement evaluation in the diagnostic work-up of MS appear more limited. Artificial intelligence tools may capture MRI attributes that are beyond the human perception, and, in the future, artificial intelligence may complement human assessment to further ameliorate the diagnostic work-up and patients’ classification. However, guidelines that ensure reliability, interpretability, and validity of findings obtained from artificial intelligence approaches are still needed to implement them in the clinical scenario. This review provides a summary of the most recent updates regarding the application of MRI for the diagnosis of MS.
Honeybees affect floral microbiome composition in a central food source for wild pollinators in boreal ecosystems
Authors: Hietaranta Elsi , Juottonen Heli , Kytöviita Minna-Maarit
Published: November 2022

Basic knowledge on dispersal of microbes in pollinator networks is essential for plant, insect, and microbial ecology. Thorough understanding of the ecological consequences of honeybee farming on these complex plant–pollinator–microbe interactions is a prerequisite for sustainable honeybee keeping. Most research on plant–pollinator–microbe interactions have focused on temperate agricultural systems. Therefore, information on a wild plant that is a seasonal bottleneck for pollinators in cold climate such asSalix phylicifoliais of specific importance. We investigated how floral visitation by insects influences the community structure of bacteria and fungi inSalix phylicifoliainflorescences under natural conditions. Insect visitors were experimentally excluded with net bags. We analyzed the microbiome and measured pollen removal in open and bagged inflorescences in sites where honeybees were foraging and in sites without honeybees. Site and plant individual explained most of the variation in floral microbial communities. Insect visitation and honeybees had a smaller but significant effect on the community composition of microbes. Honeybees had a specific effect on the inflorescence microbiome and, e.g., increased the relative abundance of operational taxonomic units (OTUs) from the bacterial order Lactobacillales. Site had a significant effect on the amount of pollen removed from inflorescences but this was not due to honeybees. Insect visitors increased bacterial and especially fungal OTU richness in the inflorescences. Pollinator visits explained 38% variation in fungal richness, but only 10% in bacterial richness. Our work shows that honeybee farming affects the floral microbiome in a wild plant in rural boreal ecosystems.
The Complexity of Two Colouring Games
Authors: Andres Stephan Dominique , Dross François , Huggan Melissa A. , Mc Inerney Fionn , Nowakowski Richard J.
Published: November 2022

We consider two variants of orthogonal colouring games on graphs. In these games, two players alternate colouring uncoloured vertices (from a choice of $$m\in {\mathbb {N}}$$

m
∈
N

colours) of a pair of isomorphic graphs while respecting the properness and the orthogonality of the partial colourings. In the normal play variant, the first player unable to move loses. In the scoring variant, each player aims to maximise their score, which is the number of coloured vertices in their copy of the graph. We prove that, given an instance with partial colourings, both the normal play and the scoring variant of the game are PSPACE-complete. An involution $$\sigma $$
σ
of a graph G is strictly matched if its fixed point set induces a clique and $$v\sigma (v)\in E(G)$$

v
σ
(
v
)
∈
E
(
G
)

for any non-fixed point $$v\in V(G)$$

v
∈
V
(
G
)

. Andres et al. (Theor Comput Sci 795:312–325, 2019) gave a solution of the normal play variant played on graphs that admit a strictly matched involution. We prove that recognising graphs that admit a strictly matched involution is NP-complete.
Retrospektive Auswertung elektronisch erhobener Patientenfragebögen einer universitären Schmerzambulanz mit dem painDETECT®-Fragebogen
Authors: Foadi N. , Winkelmann I. , Rhein M. , Karst M.
Published: November 2022

Hintergrund und Ziel der Arbeit

Psychometrische Tests können wichtige Hinweise für Diagnostik und Verlauf bei chronischen Schmerzpatienten geben. Zwischen 2008 und 2018 wurde in der Schmerzambulanz der Medizinischen Hochschule Hannover (MHH) das elektronische System painDETECT® eingesetzt. Die vorliegende retrospektive Arbeit verfolgte das Ziel, die mittels painDETECT® erfassten Daten zur Schmerzsymptomatik und die in Anspruch genommenen Therapieverfahren der in einem Zeitraum von 15 Monaten untersuchten Patientenkohorte zu evaluieren.

Material und Methoden

Es erfolgte eine statistische Analyse der erfassten schmerzbezogenen Parameter zum Zeitpunkt des Studieneinschlusses sowie im Therapieverlauf unter Einbeziehung der Ambulanzakten.

Ergebnisse

Es konnten Baseline-Daten von 459 Patienten (66 % Frauen) ausgewertet werden. Die häufigsten Krankheitsbilder waren Schmerzen im Bereich der Wirbelsäule, Kopf- und Gesichtsschmerzen und somatoforme Störungen bei meist langjähriger Vortherapie. Ca. 40 % zeigten Hinweise für neuropathische Schmerzkomponenten oder zentrale Sensibilisierung. Bei einer durchschnittlichen Schmerzintensität von VAS 6 (0–10) lag ein überwiegend hoher Chronifizierungsgrad vor. Ca. ein Drittel zeigte eine hochgradige schmerzbedingte Funktionseinschränkung. Etwas mehr als die Hälfte zeigte Hinweise auf eine klinisch relevante Depression. Ca. 80 % wiesen klinisch relevante Schlafstörungen auf. Daten zur Verlaufsbeobachtung lagen für 145 Patienten (31,6 %) vor. Der Anteil der Patienten, die eine nichtmedikamentöse Therapieform erhielten, erhöhte sich im Beobachtungszeitraum um 44,1 % (Physiotherapie) bzw. um 24,1 % (Psychotherapieverfahren). Die Verwendung von Koanalgetika stieg im Verlauf um ca. 30 %.

Diskussion

Im ambulanten Setting kann bei hochgradig chronifizierten Schmerzpatienten eine Therapieerweiterung gelingen. Enge strukturelle Vernetzungen mit den Kliniken für Rehabilitationsmedizin und für Psychosomatik und Psychotherapie der MHH können hierfür eine günstige Voraussetzung sein.
Strengthening climate research capacity in Africa: lessons from the ‘Climate impact research capacity leadership enhancement’ project
Authors: Ogega Obed M. , Lakey George , Opisa Rowland , Gyampoh Benjamin Apraku
Published: November 2022

Climate Change research plays a pivotal role in Africa’s sustainable development by providing the required scientific evidence to inform the design of Africa’s development priorities. The need for enhanced climate research is heightened by the fact that Africa is one of the regions likely to be most affected by the impacts of global warming and climate change. This paper highlights some key lessons learnt from the provision of climate research support in Africa under the Climate Impact Research Capacity Leadership Enhancement (CIRCLE) project implemented by the African Academy of Sciences and the Association of Commonwealth Universities in partnership with the United Kingdom’s Foreign, Commonwealth, and Development Office, Vitae, and the University of Greenwich’s Natural Resources Institute. The paper discusses the early-career research support landscape in Africa, the place of institutional strengthening in climate research programming, and the need for a well-coordinated community and public engagement in the climate research projects. Lessons from the CIRCLE programme provide useful insights for future climate research programme design and early-career research support initiatives in Africa.
Characterization of an advanced viable bone allograft with preserved native bone-forming cells
Authors: Gianulis Elena , Wetzell Bradley , Scheunemann Danielle , Gazzolo Patrick , Sohoni Payal , Moore Mark A. , Chen Jingsong
Published: November 2022

Bone grafts are widely used to successfully restore structure and function to patients with a broad range of musculoskeletal ailments and bone defects. Autogenous bone grafts are historically preferred because they theoretically contain the three essential components of bone healing (ie, osteoconductivity, osteoinductivity, and osteogenicity), but they have inherent limitations. Allograft bone derived from deceased human donors is one alternative that is also capable of providing both an osteoconductive scaffold and osteoinductive potential but, until recently, lacked the osteogenic component of bone healing. Relatively new, cellular bone allografts (CBAs) were designed to address this need by preserving viable cells. Although most commercially-available CBAs feature mesenchymal stem cells (MSCs), osteogenic differentiation is time-consuming and complex. A more advanced graft, a viable bone allograft (VBA), was thus developed to preserve lineage-committed bone-forming cells, which may be more suitable than MSCs to promote bone fusion. The purpose of this paper was to present the results of preclinical research characterizing VBA. Through a comprehensive series of in vitro and in vivo assays, the present results demonstrate that VBA in its final form is capable of providing all three essential bone remodeling properties and contains viable lineage-committed bone-forming cells, which do not elicit an immune response. The results are discussed in the context of clinical evidence published to date that further supports VBA as a potential alternative to autograft without the associated drawbacks.
Vergleichende Analysen der Sicherheit neuer Medikamente in Beobachtungskohorten: Wie berücksichtigt man die Veränderung von Risiken im Zeitverlauf?
Authors: Schäfer Martin , Meissner Yvette , Huschek Doreen , Zink Angela , Strangfeld Anja
Published: November 2022

Hintergrund und Ziel der Arbeit

Seit rund 20 Jahren werden in der Rheumatologie langfristig angelegte prospektive Beobachtungskohorten („Register“) geführt, die das Sicherheits- und Wirksamkeitsprofil aller innovativen Therapien vergleichend analysieren. Anders als in randomisierten klinischen Studien werden Patient:innen in der täglichen Praxis nicht nach dem Zufallsprinzip behandelt, sondern entsprechend ihrem klinischen Bedarf. Beim Vergleich von Therapiegruppen muss daher systematischen Unterschieden Rechnung getragen werden. Am Beispiel des in der Rheumatologie etablierten „RABBIT-Risikoscores für schwerwiegende Infektionen“ (entwickelt im Register RABBIT – „Rheumatoide Arthritis: Beobachtung der Biologikatherapie“) werden Methoden hierfür diskutiert.

Material und Methoden

Mit Hilfe von Propensity-Score (PS)-Methoden wurden die Patient:innen in den zu vergleichenden Gruppen so gewichtet, dass ihre Risikofaktoren zum entsprechenden Zeitpunkt balanciert waren. Diese Gewichtung wurde nicht nur zu Beobachtungsbeginn angewandt, sondern für jeden 6‑Monats-Zeitraum der Beobachtung, um die sich im Zeitverlauf verändernden Risiken sowohl auf individueller als auch auf Kohortenebene zu berücksichtigen.

Ergebnisse

Nach Beginn einer Biologikatherapie wird im Vergleich zur Standardtherapie ein erhöhtes Infektionsrisiko beobachtet, das aber im Zeitverlauf rasch abnimmt. Eine umfängliche Adjustierung in einem Poisson-Regressionsmodell kann den zeitlichen Trend erklären: Etwa ein Drittel des Rückgangs des Infektionsrisikos ist auf die unter der Therapie sinkende Krankheitsaktivität zurückzuführen, zwei Drittel begründen sich durch Kohorteneffekte wie Therapiewechsel oder Drop-out.

Schlussfolgerung

Bei Anwendung geeigneter Methoden kann in Beobachtungsdaten nicht nur für Unterschiede zu Baseline, sondern auch für Veränderungen von Risiken im Zeitverlauf adjustiert werden. Damit sind Kausalschlüsse möglich, die für die klinische Entscheidungsfindung relevant sind.
Factors affecting in vitro regeneration in the model tree Populus trichocarpa: II. Heritability estimates, correlations among explant types, and genetic interactions with treatments among wild genotypes
Authors: Ma Cathleen , Duan Chenyang , Jiang Yuan , Nagle Michael , Peremyslova Ekaterina , Goddard Amanda , Strauss Steven H.
Published: November 2022

To enhance the sensitivity of an ongoing Genome Wide Association Study (GWAS) for in vitro shoot regeneration and genetic transformation, a wide range of factors that can affect regeneration rate and, therefore, expression of genetic diversity were studied. Included were explant types and sources; direct versus indirect regeneration; nitrogen salts and micronutrient levels in basal medium; sucrose, auxin, and cytokinin types and levels; light intensity and quality; melatonin and serotonin; antibiotics (to exogenously control contaminants); antioxidants; and the ethylene-mitigating agent silver nitrate. Genotype was a statistically significant source of variance in response to nearly every treatment and for every measure of regeneration noted in shoots and roots, and initial generation of callus. Nonetheless, broad-sense heritability estimates varied widely as a result of variable degrees of environmental modification and statistical interactions with genotype. Compared to leaves, stem and petiole explants were highly correlated in their expression of genetic variation in response to treatments, a likely result of their functional similarity. Based on literature review, this study appears to be the most intensive analysis of plant natural genetic variation in response to in vitro manipulations published. It should help to guide development of improved and highly heritable treatments in other plant species that employ organogenic regeneration systems.
Orbital Cavernous Venous Malformation in a 35-Year-Old Man: A Case Report
Authors: Jaxa-Kwiatkowski A. , Tomczyk-Kurza K. , Gerber H. , Kubiak M.
Published: November 2022

In this article we present a case of a 35-year-old patient with a massive 43 × 35 × 34 mm cavernous venous malformation of the left orbit. The orbital lesion was initially observed in 2008 and remained untreated to 2021 due to the patient’s refusal to consent to the surgical procedure; which caused the tumor to grow to monstrous dimensions.
Renal FGF23 signaling depends on redox protein Memo1 and promotes orthovanadate-sensitive protein phosphotyrosyl phosphatase activity
Authors: Bartos Katalin , Ramakrishnan Suresh Krishna , Braga-Lagache Sophie , Hänzi Barbara , Durussel Fanny , Prakash Sridharan Arjun , Zhu Yao , Sheehan David , Hynes Nancy E. , Bonny Olivier , Moor Matthias B.
Published: November 2022

Memo1 deletion in mice causes premature aging and an unbalanced metabolism partially resembling Fgf23 and Klotho loss-of-function animals. We report a role for Memo’s redox function in renal FGF23-Klotho signaling using mice with postnatally induced Memo deficiency in the whole body (cKO). Memo cKO mice showed impaired FGF23-driven renal ERK phosphorylation and transcriptional responses. FGF23 actions involved activation of oxidation-sensitive protein phosphotyrosyl phosphatases in the kidney. Redox proteomics revealed excessive thiols of Rho-GDP dissociation inhibitor 1 (Rho-GDI1) in Memo cKO, and we detected a functional interaction between Memo’s redox function and oxidation at Rho-GDI1 Cys79. In isolated cellular systems, Rho-GDI1 did not directly affect FGF23-driven cell signaling, but we detected disturbed Rho-GDI1 dependent small Rho-GTPase protein abundance and activity in the kidney of Memo cKO mice. Collectively, this study reveals previously unknown layers in the regulation of renal FGF23 signaling and connects Memo with the network of small Rho-GTPases.
Profitability of Supplemental Irrigation and Soil Dewatering for Potato Production in Atlantic Canada: Insights from Historical Yield and Weather Data
Authors: Jiang Yefang , Stetson Tobin , Kostic Ana , Anderson Scott , Ramsay Matt
Published: November 2022

Highly variable and unpredictable precipitation in humid regions makes water management important for consistent potato production. This study assessed the influence of supplemental irrigation (SI) and soil dewatering on potato productivity and profitability in Prince Edward Island, Canada. The average yields of Russet Burbank (RB), Shepody, Kennebec and Goldrush cultivars from 2000 to 2020 (excluding 2018) were conceptualized as the results of an un-replicated experiment with growing season (GS) precipitation representing water supply treatment. GS precipitation varied from 155 to 479 mm, with an average of 338 mm. Yield increased with increasing GS precipitation in the 155–﻿257 mm range (Rainfall Zone 1; 3/20 seasons), became relatively insensitive to GS precipitation in the 258–425 mm range (Rainfall Zone 2; 12/20 seasons), and decreased as GS precipitation increased from 426 to 479 mm (Rainfall Zone 3; 5/20 seasons). Yields responded to GS precipitation following second-order polynomial regressions, with GS precipitation explaining 69%, 65%, 29% and 50% of yield variation for RB, Shepody, Kennebec and Goldrush cultivars, respectively. These yield regression equations predict that SI using a center-pivot system would produce a positive profit in the first half of Rainfall Zone 1 regardless of field size and in the second half of Rainfall Zone 1 in fields over 40 ha. SI would not produce a positive profit in Rainfall Zone 2 regardless of field size because precipitation was high enough that additional water supply would not have resulted in sufficient yield gains to offset the cost of SI. Soil dewatering would be beneficial for optimal production in Rainfall Zone 3 in which precipitation was excessive. The annual variation in precipitation, unpredictability of SI requirements, and unprofitability in most seasons, present a significant financial barrier for the widespread implementation of SI. On the other hand, the gross income gained from increased yields by soil dewatering would fully cover the cost of tile drain installation after only two to three extremely wet seasons, making tile drainage a good investment for consistent production. This study demonstrates that historical rain-fed yield and weather data can be used to assess the economics of potato production with SI and soil dewatering, and provides important insights on potato water management in a humid temperate climate.
Geology and lithology of the Tagay-1 section at Olkhon Island (Lake Baikal, Eastern Siberia), and description of Aplodontidae, Mylagaulidae and Sciuridae (Rodentia, Mammalia)
Authors: Daxner-Höck Gudrun , Mörs Thomas , Filinov Ivan , Shchetnikov Alexander , Erbajeva Margarita A.
Published: November 2022

Excavations along the Tagay-1 section shed light into the composition of small mammal assemblages of the Tagay site. The present paper focuses on the geology and geomorphology of Olkhon Island, the lithology and fossil evidence along the Tagay-1 section and descriptions of the aplodontid, mylagaulid and sciurid rodents. The described fossils are isolated teeth of four taxa, Ansomys sp. (Aplodontidae), Lamugaulus olkhonensis Tesakov and Lopatin, 2015 (Mylagaulidae), Sciuridae indet. and Spermophilinus debruijni nov. spec. (Sciuridae). The archaic tooth pattern of these rodents suggests an age around the Early/Middle Miocene transition.
A New Set of Criteria for Units of Selection
Authors: Bourrat Pierrick
Published: November 2022

This article proposes two conditions to assess whether an entity at a level of description is a unit of selection qua interactor. These two conditions make it possible to (1) distinguish biologically relevant entities from arbitrary ones and (2) distinguish units that can potentially enter a selection process from those that have already done so. I show that the classical approaches used in the literature on units and levels of selection do not fare well with respect to either or both of these desiderata.
Back to Chromatin: ENCODE and the Dynamic Epigenome
Authors: Lamm Ehud , Veigl Sophie Juliane
Published: November 2022

The “Encyclopedia of DNA Elements” (ENCODE) project was launched by the US National Human Genome Research Institute in the aftermath of the Human Genome Project (HGP). It aimed to systematically map the human transcriptome, and held the promise that identifying potential regulatory regions and transcription factor binding sites would help address some of the perplexing results of the HGP. Its initial results published in 2012 produced a flurry of high-impact publications as well as criticisms. Here we put the results of ENCODE and the work on epigenomics that followed in a broad theoretical and historical context, focusing on three strands of research. The first is the history of thinking about the organization of genomes, both physical and regulatory. The second is the history of ideas about gene regulation, primarily in eukaryotes. Finally, and connecting these two issues, we suggest how to think about the role of genetic material in physiology and development.
Clinic and diagnostics of house dust mite allergy
Authors: Brehler Randolf
Published: November 2022

House dust mite allergens are common triggers for allergic rhinoconjunctivitis and allergic asthma; they can aggravate atopic dermatitis and rarely lead to anaphylactic reactions due to dust mite allergens in food. Typical symptoms are nasal obstruction, sneezing, and irritation, and more often than in pollen allergy, allergic asthma also develops. The symptomatology exists in principle throughout the year with maximum complaints in autumn and winter. Of particular importance are sleep disturbances due to nasal obstruction, which lead to restrictions in the quality of life and performance of affected patients. Sensitization can be proven by skin tests and detection of serum allergen-specific IgE antibodies; proof of allergy is achieved by nasal or conjunctival provocation tests. The diagnosis of local allergic rhinitis can only be made by provocation or by determination of allergen-specific IgE antibodies in nasal secretions. The quality of the allergen extract used is essential for all tests; it must contain the allergens to which a patient is sensitized. The concentration of Der p 23 in house dust mite extracts is particularly critical.
Allergen characteristics, quality, major allergen content and galenics for mite allergen-specific immunotherapy preparations
Authors: Brehler Randolf , Klimek Ludger
Published: November 2022

House dust mite extracts for allergen-specific immunotherapy (AIT) require in Germany as other common allergens (pollen from sweet grasses [except maize], birch, alder, hazel; bee and wasp venom) marketing authorisation according to the German Therapy Allergen Ordinance (“Therapieallergene-Verordnung”, [TAV]). Mite allergen extracts that have been approved and also those which are in the approval process are subject to government batch testing. Batch test passing is a prerequisite for marketability. Appropriate quality, efficacy, and safety are prerequisites for the approval of house dust mite extracts. Five HDM allergen extracts from four manufacturers are currently approved in Germany for subcutaneous or sublingual therapy; further extracts are in the approval process. The allergen strength of different products is not comparable; manufacturers use company-specific units to describe the strength. Of the three known major allergens (Group 1 allergens: Der p 1, Der f 1, Group 2 allergens: Der p 2, Der f 2 and Group 23: Der p 23, Der f 23) only Group 1 and Group 2 allergens are usually used to standardize the extracts. Group 23 allergens are localized in the outer membrane of mite faeces, and elution requires special extraction methods. To be efficacious in a single patient an allergen extracts used for AIT must contain all allergen components against which the patient is sensitised. Based on post hoc analyses of large clinical studies, it has been proven for house dust mite tablets that Der p 23 is also contained. In Germany, the Paul Ehrlich Institute is responsible for the approval of therapeutic allergens. For the marketing authorisation information on production procedures, and quality are necessary efficacy and safety (positive benefit risk ratio) of the product must be demonstrated in clinical trials according to the current state of the art.
Salvage Logging Strongly Affects Woodpecker Abundance and Reproduction: a Meta-analysis
Authors: Basile Marco , Krištín Anton , Mikusiński Grzegorz , Thorn Simon , Żmihorski Michał , Pasinelli Gilberto , Brockerhoff Eckehard G.
Published: November 2022

Purpose of Review

Wildfires, wind storms, and pest outbreaks are the main large-scale disturbances of temperate and boreal forests, which often generate large amounts of deadwood in the landscape. Salvage and sanitation loggings (hereafter salvage logging) are usually practiced following such disturbance events and the generated deadwood is then extracted from the forest. Those practices affect a broad array of species, including fungi, lichens, invertebrates, and vertebrates that make use of deadwood either as habitat, food resource, foraging substrate, or as shelter. Woodpeckers, being a key group of forest birds dependent on deadwood, can be affected by salvage logging in two ways: (1) a reduction in the availability of food (i.e. removal of deadwood along with the saproxylic and predatory invertebrates that usually colonize dead or dying trees following forest disturbances) and (2) a decrease in potential nest sites due to the removal of dead trees. Therefore, we assessed the global effects of salvage logging on woodpecker abundance and reproduction by conducting a meta-analysis of published and unpublished data. We focused on comparing woodpeckers’ responses to forest disturbance in salvage-logged and unlogged sites. We considered different types of responses found in the literature, including abundance, occurrence, nest density, and breeding success. When analyzing the responses of woodpeckers, we also accounted for the potential effects of tree density, time since logging, elevation, latitude, and the continent.

Recent Findings

We found that both numbers and reproduction of woodpeckers were affected by salvage logging following a disturbance event. Apart from salvage logging, woodpecker responses were not significantly related to any other variables. This highlights that salvage logging can pose a substantial threat to woodpecker assemblages as well as secondary cavity-users dependent on them.

Salvage logging and related practices that affect deadwood availability should be carefully planned and preferably avoided entirely in areas important for woodpecker conservation. In managed forests, deadwood should be retained in sufficient quantities to avoid detrimental impacts on woodpeckers and on forest biodiversity in general.