bluuebunny/crossref_metadata_2025 huggingface dataset:
Freeform imaging systems: Fermat’s principle unlocks “first time right” design
Authors: Duerr Fabian , Thienpont Hugo
Published: May 2021

For more than 150 years, scientists have advanced aberration theory to describe, analyze and eliminate imperfections that disturb the imaging quality of optical components and systems. Simultaneously, they have developed optical design methods for and manufacturing techniques of imaging systems with ever-increasing complexity and performance up to the point where they are now including optical elements that are unrestricted in their surface shape. These so-called optical freeform elements offer degrees of freedom that can greatly extend the functionalities and further boost the specifications of state-of-the-art imaging systems. However, the drastically increased number of surface coefficients of these freeform surfaces poses severe challenges for the optical design process, such that the deployment of freeform optics remained limited until today. In this paper, we present a deterministic direct optical design method for freeform imaging systems based on differential equations derived from Fermat’s principle and solved using power series. The method allows calculating the optical surface coefficients that ensure minimal image blurring for each individual order of aberrations. We demonstrate the systematic, deterministic, scalable, and holistic character of our method with catoptric and catadioptric design examples. As such we introduce a disruptive methodology to design optical imaging systems from scratch, we largely reduce the “trial-and-error” approach in present-day optical design, and we pave the way to a fast-track uptake of freeform elements to create the next-generation high-end optics. We include a user application that allows users to experience this unique design method hands-on.
C/EBPβ is a MYB- and p300-cooperating pro-leukemogenic factor and promising drug target in acute myeloid leukemia
Authors: Yusenko Maria V. , Trentmann Amke , Casolari Debora A. , Abdel Ghani Luca , Lenz Mairin , Horn Melanie , Dörner Wolfgang , Klempnauer Stefan , Mootz Henning D. , Arteaga Maria Francisca , Mikesch Jan-Henrik , D’Andrea Richard J. , Gonda Thomas J. , Müller-Tidow Carsten , Schmidt Thomas J. , Klempnauer Karl-Heinz
Published: May 2021

Transcription factor MYB has recently emerged as a promising drug target for the treatment of acute myeloid leukemia (AML). Here, we have characterized a group of natural sesquiterpene lactones (STLs), previously shown to suppress MYB activity, for their potential to decrease AML cell proliferation. Unlike what was initially thought, these compounds inhibit MYB indirectly via its cooperation partner C/EBPβ. C/EBPβ-inhibitory STLs affect the expression of a large number of MYB-regulated genes, suggesting that the cooperation of MYB and C/EBPβ broadly shapes the transcriptional program of AML cells. We show that expression of GFI1, a direct MYB target gene, is controlled cooperatively by MYB, C/EBPβ, and co-activator p300, and is down-regulated by C/EBPβ-inhibitory STLs, exemplifying that they target the activity of composite MYB-C/EBPβ-p300 transcriptional modules. Ectopic expression of GFI1, a zinc-finger protein that is required for the maintenance of hematopoietic stem and progenitor cells, partially abrogated STL-induced myelomonocytic differentiation, implicating GFI1 as a relevant target of C/EBPβ-inhibitory STLs. Overall, our data identify C/EBPβ as a pro-leukemogenic factor in AML and suggest that targeting of C/EBPβ may have therapeutic potential against AML.
Glutamate and microglia activation as a driver of dendritic apoptosis: a core pathophysiological mechanism to understand schizophrenia
Authors: Parellada Eduard , Gassó Patricia
Published: May 2021

Schizophrenia disorder remains an unsolved puzzle. However, the integration of recent findings from genetics, molecular biology, neuroimaging, animal models and translational clinical research offers evidence that the synaptic overpruning hypothesis of schizophrenia needs to be reassessed. During a critical period of neurodevelopment and owing to an imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, a regionally-located glutamate storm might occur, triggering excessive dendritic pruning with the activation of local dendritic apoptosis machinery. The apoptotic loss of dendritic spines would be aggravated by microglia activation through a recently described signaling system from complement abnormalities and proteins of the MHC, thus implicating the immune system in schizophrenia. Overpruning of dendritic spines coupled with aberrant synaptic plasticity, an essential function for learning and memory, would lead to brain misconnections and synaptic inefficiency underlying the primary negative symptoms and cognitive deficits of schizophrenia. This driving hypothesis has relevant therapeutic implications, including the importance of pharmacological interventions during the prodromal phase or the transition to psychosis, targeting apoptosis, microglia cells or the glutamate storm. Future research on apoptosis and brain integrity should combine brain imaging, CSF biomarkers, animal models and cell biology.
Radiomics and radiogenomics in gliomas: a contemporary update
Authors: Singh Gagandeep , Manjila Sunil , Sakla Nicole , True Alan , Wardeh Amr H. , Beig Niha , Vaysberg Anatoliy , Matthews John , Prasanna Prateek , Spektor Vadim
Published: May 2021

The natural history and treatment landscape of primary brain tumours are complicated by the varied tumour behaviour of primary or secondary gliomas (high-grade transformation of low-grade lesions), as well as the dilemmas with identification of radiation necrosis, tumour progression, and pseudoprogression on MRI. Radiomics and radiogenomics promise to offer precise diagnosis, predict prognosis, and assess tumour response to modern chemotherapy/immunotherapy and radiation therapy. This is achieved by a triumvirate of morphological, textural, and functional signatures, derived from a high-throughput extraction of quantitative voxel-level MR image metrics. However, the lack of standardisation of acquisition parameters and inconsistent methodology between working groups have made validations unreliable, hence multi-centre studies involving heterogenous study populations are warranted. We elucidate novel radiomic and radiogenomic workflow concepts and state-of-the-art descriptors in sub-visual MR image processing, with relevant literature on applications of such machine learning techniques in glioma management.
Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells
Authors: Gao Yuge , Yao Xinyu , Zhai Yumeng , Li Li , Li Huini , Sun Xianqi , Yu Pei , Xue Tiankuo , Li Yuzhen , Hu Yizhou
Published: May 2021

Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.
Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
Authors: Mansilla M. J. , Presas-Rodríguez S. , Teniente-Serra A. , González-Larreategui I. , Quirant-Sánchez B. , Fondelli F. , Djedovic N. , Iwaszkiewicz-Grześ D. , Chwojnicki K. , Miljković Đ. , Trzonkowski P. , Ramo-Tello C. , Martínez-Cáceres E. M.
Published: May 2021

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.
A recurrent de novo ZSWIM6 variant in a Japanese patient with severe neurodevelopmental delay and frequent vomiting
Authors: Yanagishita Tomoe , Eto Kaoru , Yamamoto-Shimojima Keiko , Segawa Osamu , Nagata Miho , Ishihara Yasuki , Miyashita Yohei , Asano Yoshihiro , Sakata Yasushi , Nagata Satoru , Yamamoto Toshiyuki
Published: May 2021

A recurrent ZSWIM6 variant, NM_020928.2:c.2737C>T [p.Arg913*], was identified in a Japanese male patient with severe neurodevelopmental delay, epilepsy, distinctive facial features, microcephaly, growth deficiency, abnormal behavior, and frequent vomiting but without frontonasal or limb malformations. In this patient, distinctive facial features gradually became apparent with age, and severe vomiting caused by gastroesophageal reflux continued even after percutaneous endoscopic gastrostomy.
Structural coordination between active sites of a CRISPR reverse transcriptase-integrase complex
Authors: Wang Joy Y. , Hoel Christopher M. , Al-Shayeb Basem , Banfield Jillian F. , Brohawn Stephen G. , Doudna Jennifer A.
Published: May 2021

CRISPR-Cas systems provide adaptive immunity in bacteria and archaea, beginning with integration of foreign sequences into the host CRISPR genomic locus and followed by transcription and maturation of CRISPR RNAs (crRNAs). In some CRISPR systems, a reverse transcriptase (RT) fusion to the Cas1 integrase and Cas6 maturase creates a single protein that enables concerted sequence integration and crRNA production. To elucidate how the RT-integrase organizes distinct enzymatic activities, we present the cryo-EM structure of a Cas6-RT-Cas1—Cas2 CRISPR integrase complex. The structure reveals a heterohexamer in which the RT directly contacts the integrase and maturase domains, suggesting functional coordination between all three active sites. Together with biochemical experiments, our data support a model of sequential enzymatic activities that enable CRISPR sequence acquisition from RNA and DNA substrates. These findings highlight an expanded capacity of some CRISPR systems to acquire diverse sequences that direct CRISPR-mediated interference.
Intrinsic coupling between spatially-separated surface Fermi-arcs in Weyl orbit quantum Hall states
Authors: Nishihaya Shinichi , Uchida Masaki , Nakazawa Yusuke , Kriener Markus , Taguchi Yasujiro , Kawasaki Masashi
Published: May 2021

Topological semimetals hosting bulk Weyl points and surface Fermi-arc states are expected to realize unconventional Weyl orbits, which interconnect two surface Fermi-arc states on opposite sample surfaces under magnetic fields. While the presence of Weyl orbits has been proposed to play a vital role in recent observations of the quantum Hall effect even in three-dimensional topological semimetals, actual spatial distribution of the quantized surface transport has been experimentally elusive. Here, we demonstrate intrinsic coupling between two spatially-separated surface states in the Weyl orbits by measuring a dual-gate device of a Dirac semimetal film. Independent scans of top- and back-gate voltages reveal concomitant modulation of doubly-degenerate quantum Hall states, which is not possible in conventional surface orbits as in topological insulators. Our results evidencing the unique spatial distribution of Weyl orbits provide new opportunities for controlling the novel quantized transport by various means such as external fields and interface engineering.
On-demand synthesis of phosphoramidites
Authors: Sandahl Alexander F. , Nguyen Thuy J. D. , Hansen Rikke A. , Johansen Martin B. , Skrydstrup Troels , Gothelf Kurt V.
Published: May 2021

Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly optimised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the subsequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites.
Histological and transcriptomic analysis of adipose and muscle of dairy calves supplemented with 5-hydroxytryptophan
Authors: Field Sena L. , Marrero Marcela G. , Liu Lihe , Peñagaricano Francisco , Laporta Jimena
Published: May 2021

In mammals, peripheral serotonin is involved in regulating energy balance. Herein, we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin. Holstein bull calves (21 ± 2 days old) were fed milk replacer supplemented with saline (CON, 8 mL/day n = 4) or 5-hydroxytryptophan (5-HTP, 90 mg/day, n = 4) for 10 consecutive days. Calves were euthanized on d10 to harvest adipose and muscle for RNA-Sequencing and histological analyses. Twenty-two genes were differentially expressed in adipose, and 33 in muscle. Notably, Interferon gamma inducible protein-47 was highly expressed and upregulated in muscle and adipose (avg. log FC = 6.5). Enriched pathways in adipose tissue revealed serotonin’s participation in lipid metabolism and PPAR signaling. In muscle, enriched pathways were related to histone acetyltransferase binding, Jak-STAT signaling, PI3K-Akt signaling and cell proliferation. Supplementation of 5-HTP increased cell proliferation and total cell number in adipose and muscle. Adipocyte surface area was smaller and muscle fiber area was not different in the 5-HTP group. Manipulating the serotonin pathway, through oral supplementation of 5-HTP, influences signaling pathways and cellular processes in adipose and muscle related to endocrine and metabolic functions which might translate into improvements in calf growth and development.
Comparative analysis of liver involvement caused by two DENV-2 lineages using an immunocompetent murine model
Authors: Jácome Fernanda Cunha , Caldas Gabriela Cardoso , Rasinhas Arthur da Costa , de Almeida Ana Luisa Teixeira , de Souza Daniel Dias Coutinho , Paulino Amanda Carlos , Leonardo Raphael , Barth Ortrud Monika , dos Santos Flavia Barreto , Barreto-Vieira Débora Ferreira
Published: May 2021

Dengue (DEN) is the most prevalent arbovirus among humans, and four billion people live at risk of infection. The clinical manifestations of DEN are variable, and the disease may present subclinically or asymptomatically. A quarter of patients develop classical dengue (CD) or severe dengue (SD), which is potentially lethal and involves vascular permeability changes, severe hemorrhage and organ damage. The involvement of the liver is a fairly common feature in DEN, and alterations range from asymptomatic elevation of transaminases to acute liver failure. Since its introduction in Brazil in 1990, two strains of Dengue virus (DENV) serotype 2 (DENV-2) have been detected: Lineage I, which is responsible for an outbreak in 1991, and Lineage II, which caused an epidemic greater than the previous one and had a different epidemiological profile. To date, studies on different strains of the same serotype/genotype and their association with disease severity are scarce. In addition, one of the greatest challenges regarding the study of DEN pathogenesis and the development of drug and vaccine therapies is the absence of an animal model that reproduces the disease as it occurs in humans. The main goals of this study were to assess BALB/c mouse susceptibility experimentally infected by two distinct DENV-2 strains and characterize possible differences in the clinical signs and alterations induced in the liver resulting from those infections. Mice infected by the two DENV-2 lineages gained less weight than uninfected mice; however, their livers were slightly heavier. Increased AST and AST levels were observed in infected mice, and the number of platelets increased in the first 72 h of infection and subsequently decreased. Mice infected with both lineages presented leukocytosis but at different times of infection. The histopathological changes induced by both lineages were similar and comparable to the changes observed in DEN fatal cases. The viral genome was detected in two liver samples. The results demonstrate the susceptibility of BALB/c mice to both DENV-2 lineages and suggest that the changes induced by those strains are similar, although for some parameters, they are manifested at different times of infection.
Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
Authors: Dorandish Sadaf , Williams Asana , Atali Sarah , Sendo Sophia , Price Deanna , Thompson Colton , Guthrie Jeffrey , Heyl Deborah , Evans Hedeel Guy
Published: May 2021

In this study, we set out to identify regulators of intact amyloid-β40/42 (Aβ) levels in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher Aβ levels were detected in the media of A549 than H1299 cells without or with treatment with 4-methylumbelliferone (4-MU) and/or the anti-CD44 antibody (5F12). Using inhibitors, we found that PI3K, AKT, and NFκB are likely involved in regulating Aβ levels in the media. However, increased Aβ levels that more closely resembled those found upon 4-MU co-treatment resulted from MMP2/9 inhibition, suggesting that MMP2/9 maybe the main contributors to regulation of Aβ levels in the media. Differences in Aβ levels might be accounted for, in part, by p53 since blocking p53 function in A549 cells resulted in decreased Aβ levels, increased MMP2/9 levels, increased PI3K/AKT activities and the phospho/total NFκB ratio. Using siRNA targeted against MMP2 or MMP9, we found increased Aβ levels in the media, however, MMP2 knockdown led to Aβ levels closely mimicking those detected by co-treatment with 4-MU. Cell viability or apoptosis upon treatment with either MMP2 or MMP9 siRNA along with Aβ immunodepletion, showed that MMP2 is the predominant regulator of the cytotoxic effects induced by Aβ in lung cancer cells.
Promises and trust in human–robot interaction
Authors: Cominelli Lorenzo , Feri Francesco , Garofalo Roberto , Giannetti Caterina , Meléndez-Jiménez Miguel A. , Greco Alberto , Nardelli Mimma , Scilingo Enzo Pasquale , Kirchkamp Oliver
Published: May 2021

Understanding human trust in machine partners has become imperative due to the widespread use of intelligent machines in a variety of applications and contexts. The aim of this paper is to investigate whether human-beings trust a social robot—i.e. a human-like robot that embodies emotional states, empathy, and non-verbal communication—differently than other types of agents. To do so, we adapt the well-known economic trust-game proposed by Charness and Dufwenberg (2006) to assess whether receiving a promise from a robot increases human-trust in it. We find that receiving a promise from the robot increases the trust of the human in it, but only for individuals who perceive the robot very similar to a human-being. Importantly, we observe a similar pattern in choices when we replace the humanoid counterpart with a real human but not when it is replaced by a computer-box. Additionally, we investigate participants’ psychophysiological reaction in terms of cardiovascular and electrodermal activity. Our results highlight an increased psychophysiological arousal when the game is played with the social robot compared to the computer-box. Taken all together, these results strongly support the development of technologies enhancing the humanity of robots.
Modeling of stringent-response reflects nutrient stress induced growth impairment and essential amino acids in different Staphylococcus aureus mutants
Authors: Audretsch Christof , Gratani Fabio , Wolz Christiane , Dandekar Thomas
Published: May 2021

Stapylococcus aureus colonises the nose of healthy individuals but can also cause a wide range of infections. Amino acid (AA) synthesis and their availability is crucial to adapt to conditions encountered in vivo. Most S. aureus genomes comprise all genes required for AA biosynthesis. Nevertheless, different strains require specific sets of AAs for growth. In this study we show that regulation inactivates pathways under certain conditions which result in these observed auxotrophies. We analyzed in vitro and modeled in silico in a Boolean semiquantitative model (195 nodes, 320 edges) the regulatory impact of stringent response (SR) on AA requirement in S. aureus HG001 (wild-type) and in mutant strains lacking the metabolic regulators RSH, CodY and CcpA, respectively. Growth in medium lacking single AAs was analyzed. Results correlated qualitatively to the in silico predictions of the final model in 92% and quantitatively in 81%. Remaining gaps in our knowledge are evaluated and discussed. This in silico model is made fully available and explains how integration of different inputs is achieved in SR and AA metabolism of S. aureus. The in vitro data and in silico modeling stress the role of SR and central regulators such as CodY for AA metabolisms in S. aureus.
Studies of the potential of a native natural biosorbent for the elimination of an anionic textile dye Cibacron Blue in aqueous solution
Authors: Grabi Hocine , Derridj Fazia , Lemlikchi Wahiba , Guénin Erwann
Published: May 2021

This work is devoted to the adsorption of Cibacron Blue (CB) an anionic textile dye, on bean peel (BP) an agricultural waste with neither activation nor carbonization. The adsorption was realized in batch configuration at ambient temperature in acidic medium. The adsorbent was characterized by FTIR, SEM and BET analyses; the equilibrium isotherms and kinetics were also studied. It has been found that this waste could be used as a low-cost biosorbent for CB elimination under optimal working conditions. The rate of CB elimination reaches 95% on bean bark (3.6 g/L) at pH 2.2 and a reject concentration of 25 mg/L. The pseudo-second-order describes suitably the experimental data and the external diffusion is the rate-determining step. The Freundlich isotherm fits better the CB adsorption with a correlation coefficient (R2) of 0.94 and an RMSE = 1.5115. The negative enthalpy (ΔH) and free enthalpy (ΔG°) indicate a physical and spontaneous nature of the CB biosorption onto the biomaterial.
Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies
Authors: Chapman Asheley P. , Tang Xiaoling , Lee Joo R. , Chida Asiya , Mercer Kristina , Wharton Rebekah E. , Kainulainen Markus , Harcourt Jennifer L. , Martines Roosecelis B. , Schroeder Michelle , Zhao Liangjun , Bryksin Anton , Zhou Bin , Bergeron Eric , Bollweg Brigid C. , Tamin Azaibi , Thornburg Natalie , Wentworth David E. , Petway David , Bagarozzi Dennis A. , Finn M. G. , Goldstein Jason M.
Published: May 2021

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~ 300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nM-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.
Osmotic stress-induced somatic embryo maturation of coffee Coffea arabica L., shoot and root apical meristems development and robustness
Authors: Valencia-Lozano Eliana , Ibarra Jorge E. , Herrera-Ubaldo Humberto , De Folter Stefan , Cabrera-Ponce José L.
Published: May 2021

Somatic embryogenesis (SE) is the most important plant biotechnology process for plant regeneration, propagation, genetic transformation and genome editing of coffee, Coffea arabica L. Somatic embryo (SEs) conversion to plantlets is the principal bottleneck for basic and applied use of this process. In this study we focus on the maturation of SEs of C. arabica var. Typica. SEs conversion to plantlet up to 95.9% was achieved under osmotic stress, using 9 g/L gelrite, as compared with only 39.34% in non-osmotic stress. Mature SEs induced in osmotic stress developed shoot and root apical meristems, while untreated SEs were unable to do it. C. arabica regenerated plants from osmotic stress were robust, with higher leaf and root area and internode length. To understand a possible regulatory mechanism, gene expression of key genes of C. arabica, homologous to sequences in the Arabidopsis thaliana genome, were analyzed. A set of two component system and cytokinin signaling-related coding genes (AHK1, AHK3, AHP4 and ARR1) which interact with WUSCHEL and WOX5 homedomains and morphogenic genes, BABY-BOOM, LEC1, FUS3 and AGL15, underwent significant changes during maturation of SEs of C. arabica var. Typica. This protocol is currently being applied in genetic transformation with high rate of success.
A biomimetic peptide has no effect on the isotopic fractionation during in vitro silica precipitation
Authors: Cassarino Lucie , Curnow Paul , Hendry Katharine R.
Published: May 2021

The stable isotopic composition of diatom silica is used as a proxy for nutrient utilisation in natural waters. This approach provides essential insight into the current and historic links between biological production, carbon cycling and climate. However, estimates of isotopic fractionation during diatom silica production from both laboratory and field studies are variable, and the biochemical pathways responsible remain unknown. Here, we investigate silicon isotopic fractionation through a series of chemical precipitation experiments that are analogous to the first stages of intracellular silica formation within the diatom silicon deposition vesicle. The novelty of our experiment is the inclusion of the R5 peptide, which is closely related to a natural biomolecule known to play a role in diatom silicification. Our results suggest that the presence of R5 induces a systematic but non-significant difference in fractionation behaviour. It thus appears that silicon isotopic fractionation in vitro is largely driven by an early kinetic fractionation during rapid precipitation that correlates with the initial amount of dissolved silica in the system. Our findings raise the question of how environmental changes might impact silicon isotopic fractionation in diatoms, and whether frustule archives record information in addition to silica consumption in surface water.
Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia
Authors: Xue Yao , Chen Jing , Gao Siyuan , Zhai Xiaowen , Wang Ningling , Gao Ju , Lv Yu , Yin Mengmeng , Zhuang Yong , Zhang Hui , Zhu Xiaofan , Wu Xuedong , Li Chi Kong , Hu Shaoyan , Liang Changda , Jin Runming , Jiang Hui , Yang Minghua , Sun Lirong , Pan Kaili , Cai Jiaoyang , Tang Jingyan , Guan Xianmin , Fang Yongjun
Published: May 2021

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children’s Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 109/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6–4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6–8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0–6.9 and OR = 5.4, 95% CI = 2.0–14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.
Macrophage potentiates the recovery of liver zonation and metabolic function after acute liver injury
Authors: Miura Atsushi , Hosono Takashi , Seki Taiichiro
Published: May 2021

The liver is an exclusive organ with tremendous regenerative capacity. Liver metabolic functions exhibit spatial heterogeneity, reflecting liver zonation. The mechanisms controlling the proliferation of hepatocytes and the accompanying matrix reconstruction during regeneration have been well explored, but the recovery potential of differentiated metabolic functions and zonation after liver injury remains unclear. We employed a mouse model of carbon tetrachloride (CCl4) induced-acute liver injury with clodronate-induced macrophage depletion to clarify the impact of liver injury on liver metabolism and recovery dynamics of metabolic function and liver zonation during regeneration. Depleting macrophages suppressed tissue remodelling and partially delayed cell proliferation during regeneration after liver injury. In addition, recovery of metabolic functions was delayed by suppressing the tissue remodelling caused by the depleted macrophages. The model revealed that drug metabolic function was resilient against the dysfunction caused by liver injury, but glutamine synthesis was not. Metabolomic analysis revealed that liver branched-chain amino acid (BCAA) and carbohydrate metabolism were suppressed by injury. The plasma BCAA concentration reflected recovery of hepatic function during regeneration. Our study reveals one aspect of the regenerative machinery for hepatic metabolism following acute liver injury.
Clear phylogeographic pattern and genetic structure of wild boar Sus scrofa population in Central and Eastern Europe
Authors: Niedziałkowska Magdalena , Tarnowska Ewa , Ligmanowska Joanna , Jędrzejewska Bogumiła , Podgórski Tomasz , Radziszewska Anna , Ratajczyk Iwona , Kusza Szilvia , Bunevich Aleksei N. , Danila Gabriel , Shkvyria Maryna , Grzybowski Tomasz , Woźniak Marcin
Published: May 2021

The wild boar Sus scrofa is one of the widely spread ungulate species in Europe, yet the origin and genetic structure of the population inhabiting Central and Eastern Europe are not well recognized. We analysed 101 newly obtained sequences of complete mtDNA genomes and 548 D-loop sequences of the species and combined them with previously published data. We identified five phylogenetic clades in Europe with clear phylogeographic pattern. Two of them occurred mainly in western and central part of the continent, while the range of the third clade covered North-Eastern, Central and South-Eastern Europe. The two other clades had rather restricted distribution. In Central Europe, we identified a contact zone of three mtDNA clades. Population genetic structure reflected clear phylogeographic pattern of wild boar in this part of Europe. The contribution of lineages originating from the southern (Dinaric-Balkan) and eastern (northern cost of the Black Sea) areas to the observed phylogeographic pattern of the species in Central and Eastern Europe was larger than those from the regions located in southern France, Iberian, and Italian Peninsulas. The present work was the first mitogenomic analysis conducted in Central and Eastern Europe to study genetic diversity and structure of wild boar population.
Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
Authors: Thijssen Elisabeth H. , Verberk Inge M. W. , Vanbrabant Jeroen , Koelewijn Anne , Heijst Hans , Scheltens Philip , van der Flier Wiesje , Vanderstichele Hugo , Stoops Erik , Teunissen Charlotte E.
Published: May 2021

Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare their performance with two commercial assays. Linearity, intra- and inter-assay %CV were compared between Amyblood, Quanterix Simoa triplex, and Euroimmun ELISA. Sensitivity and selectivity were assessed for Amyblood and the Quanterix triplex. Clinical performance was assessed in CSF biomarker confirmed AD (n = 43, 68 ± 6 years) and controls (n = 42, 62 ± 5 years). Prototype and Amyblood showed similar calibrator curves and differentiation (20 AD vs 20 controls, p < 0.001). Amyblood, Quanterix triplex, and ELISA showed similar linearity (96%-122%) and intra-assay %CVs (≤ 3.1%). A minor non-specific signal was measured with Amyblood of + 2.4 pg/mL Abeta1-42 when incubated with 60 pg/mL Abeta1-40. A substantial non-specific signal of + 24.7 pg/mL Abetax-42 was obtained when 40 pg/mL Abeta3-42 was measured with the Quanterix triplex. Selectivity for Abeta1-42 at physiological Abeta1-42 and Abeta1-40 concentrations was 125% for Amyblood and 163% for Quanterix. Amyblood and Quanterix ratios (p < 0.001) and ELISA Abeta1-42 concentration (p = 0.025) could differentiate AD from controls. We successfully developed and upscaled a prototype to the Amyblood assays with similar technical and clinical performance as the Quanterix triplex and ELISA, but better specificity and selectivity than the Quanterix triplex assay. These results suggest leverage of this specific assay for monitoring treatment response in trials.
Early detection of language categories in face perception
Authors: Baus Cristina , Ruiz-Tada Elisa , Escera Carles , Costa Albert
Published: May 2021

Does language categorization influence face identification? The present study addressed this question by means of two experiments. First, to establish language categorization of faces, the memory confusion paradigm was used to create two language categories of faces, Spanish and English. Subsequently, participants underwent an oddball paradigm, in which faces that had been previously paired with one of the two languages (Spanish or English), were presented. We measured EEG perceptual differences (vMMN) between standard and two types of deviant faces: within-language category (faces sharing language with standards) or between-language category (faces paired with the other language). Participants were more likely to confuse faces within the language category than between categories, an index that faces were categorized by language. At the neural level, early vMMN were obtained for between-language category faces, but not for within-language category faces. At a later stage, however, larger vMMNs were obtained for those faces from the same language category. Our results showed that language is a relevant social cue that individuals used to categorize others and this categorization subsequently affects face perception.
A new strategy to map landslides with a generalized convolutional neural network
Authors: Prakash Nikhil , Manconi Andrea , Loew Simon
Published: May 2021

Rapid mapping of event landslides is crucial to identify the areas affected by damages as well as for effective disaster response. Traditionally, such maps are generated with visual interpretation of remote sensing imagery (manned/unmanned airborne systems or spaceborne sensors) and/or using pixel-based and object-based methods exploiting data-intensive machine learning algorithms. Recent works have explored the use of convolutional neural networks (CNN), a deep learning algorithm, for mapping landslides from remote sensing data. These methods follow a standard supervised learning workflow that involves training a model using a landslide inventory covering a relatively small area. The trained model is then used to predict landslides in the surrounding regions. Here, we propose a new strategy, i.e., a progressive CNN training relying on combined inventories to build a generalized model that can be applied directly to a new, unexplored area. We first prove the effectiveness of CNNs by training and validating on event landslides inventories in four regions after earthquakes and/or extreme meteorological events. Next, we use the trained CNNs to map landslides triggered by new events spread across different geographic regions. We found that CNNs trained on a combination of inventories have a better generalization performance, with a bias towards high precision and low recall scores. In our tests, the combined training model achieved the highest (Matthews correlation coefficient) MCC score of 0.69 when mapping landslides in new unseen regions. The mapping was done on images from different optical sensors, resampled to a spatial resolution of 6 m, 10 m, and 30 m. Despite a slightly reduced performance, the main advantage of combined training is to overcome the requirement of a local inventory for training a new deep learning model. This implementation can facilitate automated pipelines providing fast response for the generation of landslide maps in the post-disaster phase. In this study, the study areas were selected from seismically active zones with a high hydrological hazard distribution and vegetation coverage. Hence, future works should also include regions from less vegetated geographic locations.
Fermi blockade of the strong electron–phonon interaction in modelled optimally doped high temperature superconductors
Authors: Mishchenko Andrey S. , Tupitsyn Igor S. , Nagaosa Naoto , Prokof’ev Nikolay
Published: May 2021

We study how manifestations of strong electron–phonon interaction depend on the carrier concentration by solving the two-dimensional Holstein model for the spin-polarized fermions using an approximation free bold-line diagrammatic Monte Carlo method. We show that the strong electron–phonon interaction, obviously present at very small Fermion concentration, is masked by the Fermi blockade effects and Migdal’s theorem to the extent that it manifests itself as moderate one at large carriers densities. Suppression of strong electron–phonon interaction fingerprints is in agreement with experimental observations in doped high temperature superconductors.
Dynamic miRNA changes during the process of epileptogenesis in an infantile and adult-onset model
Authors: Bencurova Petra , Baloun Jiri , Hynst Jakub , Oppelt Jan , Kubova Hana , Pospisilova Sarka , Brazdil Milan
Published: May 2021

Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy. Our profiling uncovered miRNA expression characteristic for infantile and adulthood-onset epileptogenesis, suggesting the distinct biology underlying TLE in the onset age-dependent matter. Our results indicate the necessity of addressing the onset age as an important parameter in future epilepsy research.
Preliminary user centred evaluation of regional aircraft cabin interiors in virtual reality
Authors: De Crescenzio F. , Bagassi S. , Starita F.
Published: May 2021

The main aim of the CASTLE (Cabin System Design Towards Passenger Wellbeing) European project is to deliver innovative interiors solutions that maximize the comfort and wellbeing of passengers in the next future. To achieve such objective, an effective HCD (Human Centred Design) approach has been employed to derive a Human Response Model based on a holistic assessment of comfort. The overall methodology has been conceived to provide different tools and methods to collect data on the impact that the design of each cabin item has on the user from the earliest design stages. One of these tools is represented by using 3D virtual mock-ups to capture data on the user’s perception and to rate the level of appreciation inspired by the specific design. In this paper we present the experimental procedures and the results from a preliminary experimental campaign of Human in the loop simulations in Virtual/Augmented Reality of a Regional Aircraft.
A community-based randomized controlled trial providing weekly iron-folic acid supplementation increased serum- ferritin, -folate and hemoglobin concentration of adolescent girls in southern Ethiopia
Authors: Handiso Yoseph Halala , Belachew Tefera , Abuye Cherinet , Workicho Abdulhalik , Baye Kaleab
Published: May 2021

Adequate micronutrient status during adolescence can break the inter-generational cycle of malnutrition. This study evaluated the effect of community-based weekly iron-folic acid supplementation (WIFAS) on serum ferritin (SF), serum folate (SFol) and hemoglobin concentration (Hb) among adolescent girls. A community-based, individually randomized-controlled trial (RCT) was conducted in four villages of Wolaita and Hadiya zones. Adolescent girls (n = 226) aged 10–19 years were recruited and randomly assigned (n = 113/group) into: (i) WIFAS and (ii) control (no intervention) groups. Anthropometry, Hb concentration, and serum ferritin (SF), SFol, and C-reactive protein (CRP) was analyzed at baseline and endline. Baseline Hb, SF, SFol and CRP concentrations were similar in both groups (P > 0.05). About 47–49% of adolescents had marginal iron store (< 50 µg/l). Hb, SF, and SFol concentrations increased in the intervention group, but not in the control group (P < 0.05). Marginal iron store decreased from 49 to 12% after 3-months of WIFAS; whereas, the proportion of adolescents with elevated SF (> 15 µg/l) was slightly higher in the WIFAS than in the control group (P = 0.06). After adjusting for confounding factors in the multiple linear regression model, a three-months WIFAS intervention was associated with an improvement of 4.10 ng/ml in serum folate, 39.1 μg/l in serum ferritin, and 1.2 g/dl in hemoglobin concentration relative to the control group (P < 0.001). WIFAS intervention for three-months was effective in reducing iron and folate deficiency in adolescent girls. Future studies should evaluate the long-term impact of intermittent WIFAS.
Repetitive mild head trauma induces activity mediated lifelong brain deficits in a novel Drosophila model
Authors: Behnke Joseph A. , Ye Changtian , Setty Aayush , Moberg Kenneth H. , Zheng James Q.
Published: May 2021

Mild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability to brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.