bluuebunny/crossref_metadata_2025 huggingface dataset:
Solitary beam propagation in periodic layered Kerr media enables high-efficiency pulse compression and mode self-cleaning
Authors: Zhang Sheng , Fu Zongyuan , Zhu Bingbing , Fan Guangyu , Chen Yudong , Wang Shunjia , Liu Yaxin , Baltuska Andrius , Jin Cheng , Tian Chuanshan , Tao Zhensheng
Published: March 2021

Generating intense ultrashort pulses with high-quality spatial modes is crucial for ultrafast and strong-field science and can be achieved by nonlinear supercontinuum generation (SCG) and pulse compression. In this work, we propose that the generation of quasi-stationary solitons in periodic layered Kerr media can greatly enhance the nonlinear light-matter interaction and fundamentally improve the performance of SCG and pulse compression in condensed media. With both experimental and theoretical studies, we successfully identify these solitary modes and reveal their unified condition for stability. Space-time coupling is shown to strongly influence the stability of solitons, leading to variations in the spectral, spatial and temporal profiles of femtosecond pulses. Taking advantage of the unique characteristics of these solitary modes, we first demonstrate single-stage SCG and the compression of femtosecond pulses from 170 to 22 fs with an efficiency >85%. The high spatiotemporal quality of the compressed pulses is further confirmed by high-harmonic generation. We also provide evidence of efficient mode self-cleaning, which suggests rich spatiotemporal self-organization of the laser beams in a nonlinear resonator. This work offers a route towards highly efficient, simple, stable and highly flexible SCG and pulse compression solutions for state-of-the-art ytterbium laser technology.
The effect of Quorum sensing inhibitors on the evolution of CRISPR-based phage immunity in Pseudomonas aeruginosa
Authors: Broniewski Jenny M , Chisnall Matthew A W , Høyland-Kroghsbo Nina Molin , Buckling Angus , Westra Edze R
Published: March 2021

Quorum sensing controls the expression of a wide range of important traits in the opportunistic pathogen Pseudomonas aeruginosa, including the expression of virulence genes and its CRISPR-cas immune system, which protects from bacteriophage (phage) infection. This finding has led to the speculation that synthetic quorum sensing inhibitors could be used to limit the evolution of CRISPR immunity during phage therapy. Here we use experimental evolution to explore if and how a quorum sensing inhibitor influences the population and evolutionary dynamics of P. aeruginosa upon phage DMS3vir infection. We find that chemical inhibition of quorum sensing decreases phage adsorption rates due to downregulation of the Type IV pilus, which causes delayed lysis of bacterial cultures and favours the evolution of CRISPR immunity. Our data therefore suggest that inhibiting quorum sensing may reduce rather than improve the therapeutic efficacy of pilus-specific phage, and this is likely a general feature when phage receptors are positively regulated by quorum sensing.
Piezo1 channel activation in response to mechanobiological acoustic radiation force in osteoblastic cells
Authors: Zhang Guangdao , Li Xiaofei , Wu Lin , Qin Yi-Xian
Published: March 2021

Mechanobiological stimuli, such as low-intensity pulsed ultrasound (LIPUS), have been shown to promote bone regeneration and fresh fracture repair, but the fundamental biophysical mechanisms involved remain elusive. Here, we propose that a mechanosensitive ion channel of Piezo1 plays a pivotal role in the noninvasive ultrasound-induced mechanical transduction pathway to trigger downstream cellular signal processes. This study aims to investigate the expression and role of Piezo1 in MC3T3-E1 cells after LIPUS treatment. Immunofluorescence analysis shows that Piezo1 was present on MC3T3-E1 cells and could be ablated by shRNA transfection. MC3T3-E1 cell migration and proliferation were significantly increased by LIPUS stimulation, and knockdown of Piezo1 restricted the increase in cell migration and proliferation. After labeling with Fluo-8, MC3T3-E1 cells exhibited fluorescence intensity traces with several high peaks compared with the baseline during LIPUS stimulation. No obvious change in the fluorescence intensity tendency was observed after LIPUS stimulation in shRNA-Piezo1 cells, which was similar to the results in the GsMTx4-treated group. The phosphorylation ratio of ERK1/2 in MC3T3-E1 cells was significantly increased (P < 0.01) after LIPUS stimulation. In addition, Phalloidin-iFluor-labeled F-actin filaments immediately accumulated in the perinuclear region after LIPUS stimulation, continued for 5 min, and then returned to their initial levels at 30 min. These results suggest that Piezo1 can transduce LIPUS-induced mechanical signals into intracellular calcium. The influx of Ca2+ serves as a second messenger to activate ERK1/2 phosphorylation and perinuclear F-actin filament polymerization, which regulate the proliferation of MC3T3-E1 cells.
AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy
Authors: Kagiava Alexia , Karaiskos Christos , Richter Jan , Tryfonos Christina , Jennings Matthew J. , Heslegrave Amanda J. , Sargiannidou Irene , Stavrou Marina , Zetterberg Henrik , Reilly Mary M. , Christodoulou Christina , Horvath Rita , Kleopa Kleopas A.
Published: March 2021

Mutations in the GJB1 gene, encoding the gap junction (GJ) protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We developed a gene therapy approach for CMT1X using an AAV9 vector to deliver the GJB1/Cx32 gene under the myelin protein zero (Mpz) promoter for targeted expression in Schwann cells. Lumbar intrathecal injection of the AAV9-Mpz.GJB1 resulted in widespread biodistribution in the peripheral nervous system including lumbar roots, sciatic and femoral nerves, as well as in Cx32 expression in the paranodal non-compact myelin areas of myelinated fibers. A pre-, as well as post-onset treatment trial in Gjb1-null mice, demonstrated improved motor performance and sciatic nerve conduction velocities along with improved myelination and reduced inflammation in peripheral nerve tissues. Blood biomarker levels were also significantly ameliorated in treated mice. This study provides evidence that a clinically translatable AAV9-mediated gene therapy approach targeting Schwann cells could potentially treat CMT1X.
Down-regulation of Fra a 1.02 in strawberry fruits causes transcriptomic and metabolic changes compatible with an altered defense response
Authors: Orozco-Navarrete Begoña , Song Jina , Casañal Ana , Sozzani Rosangela , Flors Victor , Sánchez-Sevilla José F. , Trinkl Johanna , Hoffmann Thomas , Merchante Catharina , Schwab Wilfried , Valpuesta Victoriano
Published: March 2021

The strawberry Fra a 1 proteins belong to the class 10 Pathogenesis-Related (PR-10) superfamily. In strawberry, a large number of members have been identified, but only a limited number is expressed in the fruits. In this organ, Fra a 1.01 and Fra a 1.02 are the most abundant Fra proteins in the green and red fruits, respectively, however, their function remains unknown. To know the function of Fra a 1.02 we have generated transgenic lines that silence this gene, and performed metabolomics, RNA-Seq, and hormonal assays. Previous studies associated Fra a 1.02 to strawberry fruit color, but the analysis of anthocyanins in the ripe fruits showed no diminution in their content in the silenced lines. Gene ontology (GO) analysis of the genes differentially expressed indicated that oxidation/reduction was the most represented biological process. Redox state was not apparently altered since no changes were found in ascorbic acid and glutathione (GSH) reduced/oxidized ratio, but GSH content was reduced in the silenced fruits. In addition, a number of glutathione-S-transferases (GST) were down-regulated as result of Fra a 1.02-silencing. Another highly represented GO category was transport which included a number of ABC and MATE transporters. Among the regulatory genes differentially expressed WRKY33.1 and WRKY33.2 were down-regulated, which had previously been assigned a role in strawberry plant defense. A reduced expression of the VQ23 gene and a diminished content of the hormones JA, SA, and IAA were also found. These data might indicate that Fra a 1.02 participates in the defense against pathogens in the ripe strawberry fruits.
Methyl jasmonate mediates melatonin-induced cold tolerance of grafted watermelon plants
Authors: Li Hao , Guo Yanliang , Lan Zhixiang , Xu Kai , Chang Jingjing , Ahammed Golam Jalal , Ma Jianxiang , Wei Chunhua , Zhang Xian
Published: March 2021

Root–shoot communication has a critical role in plant adaptation to environmental stress. Grafting is widely applied to enhance the abiotic stress tolerance of many horticultural crop species; however, the signal transduction mechanism involved in this tolerance remains unknown. Here, we show that pumpkin- or figleaf gourd rootstock-enhanced cold tolerance of watermelon shoots is accompanied by increases in the accumulation of melatonin, methyl jasmonate (MeJA), and hydrogen peroxide (H2O2). Increased melatonin levels in leaves were associated with both increased melatonin in rootstocks and MeJA-induced melatonin biosynthesis in leaves of plants under cold stress. Exogenous melatonin increased the accumulation of MeJA and H2O2 and enhanced cold tolerance, while inhibition of melatonin accumulation attenuated rootstock-induced MeJA and H2O2 accumulation and cold tolerance. MeJA application induced H2O2 accumulation and cold tolerance, but inhibition of JA biosynthesis abolished rootstock- or melatonin-induced H2O2 accumulation and cold tolerance. Additionally, inhibition of H2O2 production attenuated MeJA-induced tolerance to cold stress. Taken together, our results suggest that melatonin is involved in grafting-induced cold tolerance by inducing the accumulation of MeJA and H2O2. MeJA subsequently increases melatonin accumulation, forming a self-amplifying feedback loop that leads to increased H2O2 accumulation and cold tolerance. This study reveals a novel regulatory mechanism of rootstock-induced cold tolerance.
Towards explicit regulating-ion-transport: nanochannels with only function-elements at outer-surface
Authors: Ma Qun , Li Yu , Wang Rongsheng , Xu Hongquan , Du Qiujiao , Gao Pengcheng , Xia Fan
Published: March 2021

Function elements (FE) are vital components of nanochannel-systems for artificially regulating ion transport. Conventionally, the FE at inner wall (FEIW) of nanochannel−systems are of concern owing to their recognized effect on the compression of ionic passageways. However, their properties are inexplicit or generally presumed from the properties of the FE at outer surface (FEOS), which will bring potential errors. Here, we show that the FEOS independently regulate ion transport in a nanochannel−system without FEIW. The numerical simulations, assigned the measured parameters of FEOS to the Poisson and Nernst-Planck (PNP) equations, are well fitted with the experiments, indicating the generally explicit regulating-ion-transport accomplished by FEOS without FEIW. Meanwhile, the FEOS fulfill the key features of the pervious nanochannel systems on regulating-ion-transport in osmotic energy conversion devices and biosensors, and show advantages to (1) promote power density through concentrating FE at outer surface, bringing increase of ionic selectivity but no obvious change in internal resistance; (2) accommodate probes or targets with size beyond the diameter of nanochannels. Nanochannel-systems with only FEOS of explicit properties provide a quantitative platform for studying substrate transport phenomena through nanoconfined space, including nanopores, nanochannels, nanopipettes, porous membranes and two-dimensional channels.
The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites
Authors: Mendes Karina , Schmidhofer Sandra , Minderjahn Julia , Glatz Dagmar , Kiesewetter Claudia , Raithel Johanna , Wimmer Julia , Gebhard Claudia , Rehli Michael
Published: March 2021

The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites.
Study on a new type of environment-friendly polymer and its preliminary application as soil consolidation agent during tree transplanting
Authors: Wang Shaoli , Wei Donglu , Yang Xuping , Song Shengju , Sun Lifang , Xin Xuebing , Zheng Guangshun , Wang Ran , Liu LiLi , Sun Jingshuang , Wang Haixia , Lv Fuling , Mo Wenjuan , Wang Hong , Luo Chaoxing , Xiong Zhengqi , Wang Shaobo , Li Shaofeng , Xia Yongxiu
Published: March 2021

Transplanting trees with rhizospheric soil is an important way to facilitate tree survival in the process of landscaping and reforestation. Traditional way to prevent looseness of rhizospheric soil is forming soil balls around the roots with bags, boxes or rope wrapping, which is cumbersome, laborious and easy to break. This study is aimed to develop a new type of degradable environment-friendly polymer as soil consolidation agent to facilitate tree transplanting. In this paper, the KGM/CA/PVA ternary blending soil consolidation agent was prepared by using Konjac glucomannan (KGM), chitosan (CA) and polyvinyl alcohol (PVA) as raw materials. Through the verification and evaluation, the clay and sandy soil can be consolidated and formed into soil balls by the ternary blend adhesive, which was convenient for transportation. The preliminary application of the ternary blend adhesive in the transplanting process of sierra salvia, Japanese Spindle (Euonymus japonicus) and Juniperus sabina ‘Tamaricifolia’ confirmed that the application of soil consolidation agent can effectively solve the problem that the root ball of seedling is easily broken in the process of transplant. And the application of soil consolidation agent has no adverse effect on the growth of transplanted seedlings. The research and development of ternary blending soil consolidation agent and its preliminary application in seedling transplanting will provide a new solution to solve the problem of soil ball breakage in the process of seedling transplanting. This is an important stage in the development of new seedling transplanting technology. Therefore, the research and development of soil consolidation agent is of great significance.
Comparison of leucine-rich alpha-2-glycoprotein-1 (LRG-1) plasma levels between patients with and without appendicitis, a case–controlled study
Authors: Lontra Marcelo Bentancor , Savaris Ricardo F. , Cavazzola Leandro Totti , Maissiat Jackson
Published: March 2021

Acute appendicitis (AA) is the first cause of emergency surgery. Leucine-Rich Alpha-2-Glycoprotein 1 (LRG1) has been shown to be a potential biomarker in cases of AA in children, but there are conflicting results for its use in adults. The objective of this study is to compare the median plasma values of LRG1 in patients with acute abdomen with and without appendicitis. This case–control study was conducted prospectively at the emergency room (ER) of a tertiary teaching hospital, between March 1st, 2011 and December 31st, 2012. Patients with recent abdominal pain, aged 18–70 years who attended at the ER were included in the study. Blood samples were drawn at the first presentation. Those who were submitted to surgery and had a pathology report of AA were considered as cases. Those without a need for surgery and treated for other conditions, e.g., pelvic inflammatory disease, were considered as controls. Follow-up in controls was made up to 30 days. LRG1 plasma median values were measured using an ELISA kit and compared between groups. A total of 28 participants, 14 cases with acute appendicitis and 14 controls, were included. The median (range) values of leucine-rich alpha-2-glycoprotein-1 level in the group with appendicitis and control group were 8.8 ng/ml (5.5–31) and 11 (4.6–108) ng/ml, respectively (Mann–Whitney test P = 0.26). Median plasma leucine-rich alpha-2-glycoprotein-1 levels were not useful in diagnosing Acute Appendicitis in patients with acute abdominal pain.
DAAM2 is elevated in the circulation and placenta in pregnancies complicated by fetal growth restriction and is regulated by hypoxia
Authors: de Alwis Natasha , Beard Sally , Binder Natalie K. , Pritchard Natasha , Kaitu’u-Lino Tu’uhevaha J. , Walker Susan P. , Stock Owen , Groom Katie , Petersen Scott , Henry Amanda , Said Joanne M. , Seeho Sean , Kane Stefan C. , Hui Lisa , Tong Stephen , Hannan Natalie J.
Published: March 2021

Previously, we identified increased maternal circulating DAAM2 mRNA in pregnancies complicated by preterm fetal growth restriction (FGR). Here, we assessed whether circulating DAAM2 mRNA could detect FGR, and whether the DAAM2 gene, known to play roles in the Wnt signalling pathway is expressed in human placenta and associated with dysfunction and FGR. We performed linear regression analysis to calculate area under the ROC curve (AUC) for DAAM2 mRNA expression in the maternal circulation of pregnancies complicated by preterm FGR. DAAM2 mRNA expression was assessed across gestation by qPCR. DAAM2 protein and mRNA expression was assessed in preterm FGR placenta using western blot and qPCR. DAAM2 expression was assessed in term cytotrophoblasts and placental explant tissue cultured under hypoxic and normoxic conditions by qPCR. Small interfering RNAs were used to silence DAAM2 in term primary cytotrophoblasts. Expression of growth, apoptosis and oxidative stress genes were assessed by qPCR. Circulating DAAM2 mRNA was elevated in pregnancies complicated by preterm FGR [p < 0.0001, AUC = 0.83 (0.78–0.89)]. Placental DAAM2 mRNA was detectable across gestation, with highest expression at term. DAAM2 protein was increased in preterm FGR placentas but demonstrated no change in mRNA expression. DAAM2 mRNA expression was increased in cytotrophoblasts and placental explants under hypoxia. Silencing DAAM2 under hypoxia decreased expression of pro-survival gene, BCL2 and oxidative stress marker, NOX4, whilst increasing expression of antioxidant enzyme, HMOX-1. The increased DAAM2 associated with FGR and hypoxia implicates a potential role in placental dysfunction. Decreasing DAAM2 may have cytoprotective effects, but further research is required to elucidate its role in healthy and dysfunctional placentas.
The structure dilemma in biological and artificial neural networks
Authors: Pircher Thomas , Pircher Bianca , Schlücker Eberhard , Feigenspan Andreas
Published: March 2021

Brain research up to date has revealed that structure and function are highly related. Thus, for example, studies have repeatedly shown that the brains of patients suffering from schizophrenia or other diseases have a different connectome compared to healthy people. Apart from stochastic processes, however, an inherent logic describing how neurons connect to each other has not yet been identified. We revisited this structural dilemma by comparing and analyzing artificial and biological-based neural networks. Namely, we used feed-forward and recurrent artificial neural networks as well as networks based on the structure of the micro-connectome ofC. elegansand of the human macro-connectome. We trained these diverse networks, which markedly differ in their architecture, initialization and pruning technique, and we found remarkable parallels between biological-based and artificial neural networks, as we were additionally able to show that the dilemma is also present in artificial neural networks. Our findings show that structure contains all the information, but that this structure is not exclusive. Indeed, the same structure was able to solve completely different problems with only minimal adjustments. We particularly put interest on the influence of weights and the neuron offset value, as they show a different adaption behaviour. Our findings open up new questions in the fields of artificial and biological information processing research.
Utilizing distributed acoustic sensing and ocean bottom fiber optic cables for submarine structural characterization
Authors: Cheng Feng , Chi Benxin , Lindsey Nathaniel J. , Dawe T. Craig , Ajo-Franklin Jonathan B.
Published: March 2021

The sparsity of permanent seismic instrumentation in marine environments often limits the availability of subsea information on geohazards, including active fault systems, in both time and space. One sensing resource that provides observational access to the seafloor environment are existing networks of ocean bottom fiber optic cables; these cables, coupled to modern distributed acoustic sensing (DAS) systems, can provide dense arrays of broadband seismic observations capable of recording both seismic events and the ambient noise wavefield. Here, we report a marine DAS application which demonstrates the strength and limitation of this new technique on submarine structural characterization. Based on ambient noise DAS records on a 20 km section of a fiber optic cable offshore of Moss Landing, CA, in Monterey Bay, we extract Scholte waves from DAS ambient noise records using interferometry techniques and invert the resulting multimodal dispersion curves to recover a high resolution 2D shear-wave velocity image of the near seafloor sediments. We show for the first time that the migration of coherently scattered Scholte waves observed on DAS records can provide an approach for resolving sharp lateral contrasts in subsurface properties, particularly shallow faults and depositional features near the seafloor. Our results provide improved constraints on shallow submarine features in Monterey Bay, including fault zones and paleo-channel deposits, thus highlighting one of many possible geophysical uses of the marine cable network.
Transition from continental rifting to oceanic spreading in the northern Red Sea area
Authors: El Khrepy Sami , Koulakov Ivan , Gerya Taras , Al-Arifi Nassir , Alajmi Mamdouh S. , Qadrouh Ayman N.
Published: March 2021

Lithosphere extension, which plays an essential role in plate tectonics, occurs both in continents (as rift systems) and oceans (spreading along mid-oceanic ridges). The northern Red Sea area is a unique natural geodynamic laboratory, where the ongoing transition from continental rifting to oceanic spreading can be observed. Here, we analyze travel time data from a merged catalogue provided by the Egyptian and Saudi Arabian seismic networks to build a three-dimensional model of seismic velocities in the crust and uppermost mantle beneath the northern Red Sea and surroundings. The derived structures clearly reveal a high-velocity anomaly coinciding with the Red Sea basin and a narrow low-velocity anomaly centered along the rift axis. We interpret these structures as a transition of lithospheric extension from continental rifting to oceanic spreading. The transitional lithosphere is manifested by a dominantly positive seismic anomaly indicating the presence of a 50–70-km-thick and 200–300-km-wide cold lithosphere. Along the forming oceanic ridge axis, an elongated low-velocity anomaly marks a narrow localized nascent spreading zone that disrupts the transitional lithosphere. Along the eastern margins of the Red Sea, several low-velocity anomalies may represent crustal zone of massive Cenozoic basaltic magmatism.
Safety and effectiveness of kidney transplantation using a donation after brain death donor with acute kidney injury: a retrospective cohort study
Authors: Kim Kyeong Deok , Lee Kyo Won , Kim Sang Jin , Lee Okjoo , Lim Manuel , Jeong Eun Sung , Kwon Jieun , Yang Jaehun , Oh Jongwook , Park Jae Berm
Published: March 2021

The use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.
Telomere attrition rates are associated with weather conditions and predict productive lifespan in dairy cattle
Authors: Seeker Luise A. , Underwood Sarah L. , Wilbourn Rachael V. , Dorrens Jennifer , Froy Hannah , Holland Rebecca , Ilska Joanna J. , Psifidi Androniki , Bagnall Ainsley , Whitelaw Bruce , Coffey Mike , Banos Georgios , Nussey Daniel H.
Published: March 2021

Telomere length is predictive of adult health and survival across vertebrate species. However, we currently do not know whether such associations result from among-individual differences in telomere length determined genetically or by early-life environmental conditions, or from differences in the rate of telomere attrition over the course of life that might be affected by environmental conditions. Here, we measured relative leukocyte telomere length (RLTL) multiple times across the entire lifespan of dairy cattle in a research population that is closely monitored for health and milk production and where individuals are predominantly culled in response to health issues. Animals varied in their change in RLTL between subsequent measurements and RLTL shortened more during early life and following hotter summers which are known to cause heat stress in dairy cows. The average amount of telomere attrition calculated over multiple repeat samples of individuals predicted a shorter productive lifespan, suggesting a link between telomere loss and health. TL attrition was a better predictor of when an animal was culled than their average TL or the previously for this population reported significant TL at the age of 1 year. Our present results support the hypothesis that TL is a flexible trait that is affected by environmental factors and that telomere attrition is linked to animal health and survival traits. Change in telomere length may represent a useful biomarker in animal welfare studies.
Optical Tweezers with Integrated Multiplane Microscopy (OpTIMuM): a new tool for 3D microrheology
Authors: Matheson Andrew B. , Paterson Lynn , Wright Amanda J. , Mendonca Tania , Tassieri Manlio , Dalgarno Paul A.
Published: March 2021

We introduce a novel 3D microrheology system that combines for the first time Optical Tweezers with Integrated Multiplane Microscopy (OpTIMuM). The system allows the 3D tracking of an optically trapped bead, with ~ 20 nm accuracy along the optical axis. This is achieved without the need for a high precision z-stage, separate calibration sample, nor a priori knowledge of either the bead size or the optical properties of the suspending medium. Instead, we have developed a simple yet effective in situ spatial calibration method using image sharpness and exploiting the fact we image at multiple planes simultaneously. These features make OpTIMuM an ideal system for microrheology measurements, and we corroborate the effectiveness of this novel microrheology tool by measuring the viscosity of water in three dimensions, simultaneously.
Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome
Authors: Moore Robert , Puniya Bhanwar Lal , Powers Robert , Guda Chittibabu , Bayles Kenneth W. , Berkowitz David B. , Helikar Tomáš
Published: March 2021

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed through literature to have shown radioprotective effect upon perturbation. This study provided a new perspective for the treatment of ARS using systems-level gene associations integrated with multiple biological information. The identified genes might provide high confidence drug target candidates for potential drug repurposing for ARS.
“Intracascaral space” an eggshell structure of Caiman latirostris eggs
Authors: Piazza Mila V. , Fernández Mariela S. , Leiva Pamela M. L. , Piña Carlos I. , Simoncini Melina S.
Published: March 2021

In recent decades, eggshells of eggs from large-bodied reptiles have been studied by many researchers, to describe the eggshell, to compare them to extinct lineages that once inhabited our planet and also to understand how the egg provides the embryo specific conditions during incubation. In previous studies we described and characterized normal and pathologic Caiman latirostris eggshells; we also evaluated how the eggshell changes during incubation. In a study relating temperature variation and eggshell structures of successful eggs, we observed empty structures not previously described that we termed “intracascaral space”. The aim of this study is to describe this structure of C. latirostris eggshells. We hypothesize about the possible functions which it would perform during incubation and for development of the embryos.
BASP1 labels neural stem cells in the neurogenic niches of mammalian brain
Authors: Manganas Louis N. , Durá Irene , Osenberg Sivan , Semerci Fatih , Tosun Mehmet , Mishra Rachana , Parkitny Luke , Encinas Juan M. , Maletic-Savatic Mirjana
Published: March 2021

The mechanisms responsible for determining neural stem cell fate are numerous and complex. To begin to identify the specific components involved in these processes, we generated several mouse neural stem cell (NSC) antibodies against cultured mouse embryonic neurospheres. Our immunohistochemical data showed that the NSC-6 antibody recognized NSCs in the developing and postnatal murine brains as well as in human brain organoids. Mass spectrometry revealed the identity of the NSC-6 epitope as brain abundant, membrane-attached signal protein 1 (BASP1), a signaling protein that plays a key role in neurite outgrowth and plasticity. Western blot analysis using the NSC-6 antibody demonstrated multiple BASP1 isoforms with varying degrees of expression and correlating with distinct developmental stages. Herein, we describe the expression of BASP1 in NSCs in the developing and postnatal mammalian brains and human brain organoids, and demonstrate that the NSC-6 antibody may be a useful marker of these cells.
Traits and risk factors of post-disaster infectious disease outbreaks: a systematic review
Authors: Charnley Gina E. C. , Kelman Ilan , Gaythorpe Katy A. M. , Murray Kris A.
Published: March 2021

Infectious disease outbreaks are increasingly recognised as events that exacerbate impacts or prolong recovery following disasters. Yet, our understanding of the frequency, geography, characteristics and risk factors of post-disaster disease outbreaks globally is lacking. This limits the extent to which disease outbreak risks can be prepared for, monitored and responded to following disasters. Here, we conducted a global systematic review of post-disaster outbreaks and found that outbreaks linked to conflicts and hydrological events were most frequently reported, and most often caused by bacterial and water-borne agents. Lack of adequate WASH facilities and poor housing were commonly reported risk factors. Displacement, through infrastructure damage, can lead to risk cascades for disease outbreaks; however, displacement can also be an opportunity to remove people from danger and ultimately protect health. The results shed new light on post-disaster disease outbreaks and their risks. Understanding these risk factors and cascades, could help improve future region-specific disaster risk reduction.
Galectin-9 expression correlates with therapeutic effect in rheumatoid arthritis
Authors: Sun Jiao , Sui Yameng , Wang Yunqing , Song Lijun , Li Dong , Li Guosheng , Liu Jianwei , Shu Qiang
Published: March 2021

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Active RA patients were enrolled and treated with tacrolimus (TAC) alone or in combination therapy for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and week 12. We measured Gal-9 expression in different T cell subsets and in plasma. The disease activity of RA patients decreased after treatment. At baseline, the Gal-9 expression percentage was higher in the group with severe disease than in mild or moderate groups. After treatment, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8− cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. Gal-9 can be regarded as a new biomarker for evaluating RA activity and therapeutic effect, including TAC.
A machine learning approach to personalized dose adjustment of lamotrigine using noninvasive clinical parameters
Authors: Zhu Xiuqing , Huang Wencan , Lu Haoyang , Wang Zhanzhang , Ni Xiaojia , Hu Jinqing , Deng Shuhua , Tan Yaqian , Li Lu , Zhang Ming , Qiu Chang , Luo Yayan , Chen Hongzhen , Huang Shanqing , Xiao Tao , Shang Dewei , Wen Yuguan
Published: March 2021

The pharmacokinetic variability of lamotrigine (LTG) plays a significant role in its dosing requirements. Our goal here was to use noninvasive clinical parameters to predict the dose-adjusted concentrations (C/D ratio) of LTG based on machine learning (ML) algorithms. A total of 1141 therapeutic drug-monitoring measurements were used, 80% of which were randomly selected as the "derivation cohort" to develop the prediction algorithm, and the remaining 20% constituted the "validation cohort" to test the finally selected model. Fifteen ML models were optimized and evaluated by tenfold cross-validation on the "derivation cohort,” and were filtered by the mean absolute error (MAE). On the whole, the nonlinear models outperformed the linear models. The extra-trees’ regression algorithm delivered good performance, and was chosen to establish the predictive model. The important features were then analyzed and parameters of the model adjusted to develop the best prediction model, which accurately described the C/D ratio of LTG, especially in the intermediate-to-high range (≥ 22.1 μg mL−1 g−1 day), as illustrated by a minimal bias (mean relative error (%) =  + 3%), good precision (MAE = 8.7 μg mL−1 g−1 day), and a high percentage of predictions within ± 20% of the empirical values (60.47%). This is the first study, to the best of our knowledge, to use ML algorithms to predict the C/D ratio of LTG. The results here can help clinicians adjust doses of LTG administered to patients to minimize adverse reactions.
Profiling of CYP4Z1 and CYP1B1 expression in bladder cancers
Authors: Al-saraireh Yousef M. , Alshammari Fatemah O. F. O. , Youssef Ahmed M. M. , Al-Sarayreh Sameeh , Almuhaisen Ghadeer H. , Alnawaiseh Nedal , Al Shuneigat Jehad M. , Alrawashdeh Hamzeh M.
Published: March 2021

Bladder cancer is the tenth most common cancer worldwide, where its burden remains a challenge and needs new novel therapies. Several reports indicate expression of CYP4Z1 and CYP1B1 in many tumours. Their expressions are associated with a poor prognosis, and therefore proposed as promising biomarkers or targets for anticancer therapy. By using immunohistochemistry, expression of CYP4Z1 and CYP1B1 was evaluated in a panel of different types of bladder cancer, and the enzymes’ relation to histopathological features were assessed. Results showed an increased expression of CYP4Z1 (54.3%) and CYP1B1 (76.9%) in the majority of bladder cancers compared to weak or lack of expression of both enzymes in normal tissues. CYP4Z1expression was significantly associated with tumour grade and stage where the expression was markedly increased in a high grade and advanced stage of the disease (p < 0.05). Additionally, CYP1B1 expression was also associated with TNM staging (p < 0.05) and its expression was increased in patients with lymph node metastasis. The expression profiles of CYP4Z1 and CYP1B1 suggest that both enzymes have the potential to be biomarkers or targets for novel anticancer therapy for bladder cancer. Nevertheless, further studies are needed to better delineate whether these enzymes are druggable targets.
Intercalation as a versatile tool for fabrication, property tuning, and phase transitions in 2D materials
Authors: Rajapakse Manthila , Karki Bhupendra , Abu Usman O. , Pishgar Sahar , Musa Md Rajib Khan , Riyadh S. M. Shah , Yu Ming , Sumanasekera Gamini , Jasinski Jacek B.
Published: March 2021

Recent advances in two-dimensional (2D) materials have led to the renewed interest in intercalation as a powerful fabrication and processing tool. Intercalation is an effective method of modifying the interlayer interactions, doping 2D materials, modifying their electronic structure or even converting them into starkly different new structures or phases. Herein, we discuss different methods of intercalation and provide a comprehensive review of various roles and applications of intercalation in next‐generation energy storage, optoelectronics, thermoelectrics, catalysis, etc. The recent progress in intercalation effects on crystal structure and structural phase transitions, including the emergence of quantum phases are also reviewed.
Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
Authors: Pajed Laura , Taschler Ulrike , Tilp Anna , Hofer Peter , Kotzbeck Petra , Kolleritsch Stephanie , Radner Franz P. W. , Pototschnig Isabella , Wagner Carina , Schratter Margarita , Eder Sandra , Huetter Sabrina , Schreiber Renate , Haemmerle Guenter , Eichmann Thomas O. , Schweiger Martina , Hoefler Gerald , Kershaw Erin E. , Lass Achim , Schoiswohl Gabriele
Published: March 2021

Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.
Effects of natural and experimental drought on soil fungi and biogeochemistry in an Amazon rain forest
Authors: Buscardo Erika , Souza Rômulo C. , Meir Patrick , Geml József , Schmidt Steven K. , da Costa Antônio C. L. , Nagy Laszlo
Published: March 2021

Microbiota are essential components of the soil, driving biogeochemical cycles. Fungi affect decomposition and biotic interactions with plants across scales. Climate projections suggest that extended dry seasons may transform sensitive rain forests into savanna-like vegetation, with consequent changes in biogeochemistry. Here we compare the impacts of natural seasonality with 14 years of partial throughfall exclusion in an Amazonian rain forest, focussing on soil fungal functional diversity, extracellular soil enzyme activities (EEA) and their implications for nutrient dynamics. Large changes in fungal diversity and functional group composition occur in response to drought, with a conspicuous increase in the abundance of dark-septate fungi and a decrease in fungal pathogens. The high seasonality of EEA in the control (non droughted) and suppression of seasonality in the drought treatment, together with an increased implied nitrogen demand in the dry season induced by experimental drought, suggest that the changed soil microbiota activity may signal a pending shift in the biogeochemical functioning of the forest.
A microfluidic microparticle-labeled impedance sensor array for enhancing immunoassay sensitivity
Authors: Khodayari Bavil Ali , Sticker Drago , Rothbauer Mario , Ertl Peter , Kim Jungkyu
Published: March 2021

A microfluidic impedance biosensor incorporated with various microparticles is introduced for signal enhancement to realize a digital point-of-care diagnostic platform.
Stibine as a reagent in molecular chemistry - targeted synthesis of primary and secondary stibanyl-gallanes and their lighter homologues
Authors: Schneider Selina , Ivlev Sergei , von Hänisch Carsten
Published: March 2021

For the first time, SbH3 has been successfully used as a synthon in molecular chemistry. The reaction of SbH3 with (Dipp2NacNac)Ga proceeds under the oxidative addition of a Sb–H bond to the gallium atom.
Comment on “Impact of water on the BrO + HO2 gas-phase reaction: mechanism, kinetics and products” by N. T. Tsona, S. Tang and L. Du, Phys. Chem. Chem. Phys., 2019, 21, 20296
Authors: Chow Ronald , Mok Daniel K. W. , Lee Edmond P. F. , Dyke John M.
Published: March 2021

The results of the work of Tsona et al. are at variance with the earlier computational work performed by Chow et al. (PCCP 2016, 18, 30554–30569). Reasons for this are presented.
Pt(iv) complexes based on cyclohexanediamines and the histone deacetylase inhibitor 2-(2-propynyl)octanoic acid: synthesis, characterization, cell penetration properties and antitumor activity
Authors: Gabano Elisabetta , Rangone Beatrice , Perin Elena , Caron Giulia , Ermondi Giuseppe , Vallaro Maura , Gandin Valentina , Marzano Cristina , Barbanente Alessandra , Margiotta Nicola , Ravera Mauro
Published: March 2021

Combinations of different cyclohexanediamines and 2-(2-propynyl)octanoate in Pt(iv) complexes resulted in prodrug candidates with promising antiproliferative and in vivo antitumor activity.
A PEGylated photosensitizer-core pH-responsive polymeric nanocarrier for imaging-guided combination chemotherapy and photodynamic therapy
Authors: Chang Zhijian , Ye Jia-Hai , Qi Fen , Fang Hongbao , Lin Fuyan , Wang Shuai , Mu Cancan , Zhang Wenchao , He Weijiang
Published: March 2021

A novel chemo-photodynamic combined therapeutic self-assembly polymeric platform (MPEG-Hyd-Br2-BODIPY) was constructed which can encapsulate DOX and exhibited an accelerated release rate with decreasing pH value which results in considerable time/dose-dependent cytotoxicity.
Debye vs. Casimir: controlling the structure of charged nanoparticles deposited on a substrate
Authors: Vasilyev Oleg A. , Marino Emanuele , Kluft Bas B. , Schall Peter , Kondrat Svyatoslav
Published: March 2021

Multiscale simulations and experiments show how to control the structure of deposited nanoparticles by combining the Debye-screened electrostatic repulsion and critical Casimir attraction.
Titanium and nitrogen co-doped porous carbon for high-performance supercapacitors
Authors: Chen Yurou , Feng Xin , Wang Qi , Gu WenXian , Wu Wanyi , Peng Xuqiang , Jin Huile , Wang Jichang , Wang Shun
Published: March 2021

This work presents a simple solvothermal method to synthesize Ti, N co-doped carbon materials, in which the inclusion of a small amount of transition metal Ti significantly improved their electrochemical capacitive performance.
Synthesis and antimicrobial activities of chitosan/polypropylene carbonate-based nanoparticles
Authors: Quan Zhilong , Luo Chunyang , Zhu Bitong , Zhao Chungui , Yang Mingyi , Bjørås Magnar , Zhu Kaizheng , Kjøniksen Anna-Lena
Published: March 2021

Chitosan-graft-polypropylene carbonate polymers (M-type) and microgels (G-type) exhibit high antimicrobial activity against E. coli and S. aureus and display no hemolytic activity towards mouse red blood cells in neutral medium.
Reversible and irreversible membrane fouling in hollow-fiber UF membranes filtering surface water: effects of ozone/powdered activated carbon treatment
Authors: Huang Weiwei , Zhu Yuanhong , Wang Lin , Lv Weiguang , Dong Bingzhi , Zhou Wenzong
Published: March 2021

This study investigated the reversible and irreversible membrane fouling behavior of micro polluted water by ozone/powdered activated carbon (PAC)/ultrafiltration treatment.
Thermal stability and structure of glyceraldehyde-3-phosphate dehydrogenase from the coral Acropora millepora
Authors: Perez Astrid M. , Wolfe Jacob A. , Schermerhorn Janse T. , Qian Yiwen , Cela Bekim A. , Kalinowski Cody R. , Largoza Garrett E. , Fields Peter A. , Brandt Gabriel S.
Published: March 2021

The thermal stability of a critical coral metabolic enzyme increases significantly in the presence of its cofactor. X-ray crystallography identifies the protein backbone changes associated with cofactor occupancy.
SrTi(IO3)6·2H2O and SrSn(IO3)6: distinct arrangements of lone pair electrons leading to large birefringences
Authors: Liu Kaitong , Han Jian , Huang Junben , Wei Zhonglei , Yang Zhihua , Pan Shilie
Published: March 2021

The distinct arrangements of [IO3]− trigonal pyramids lead to larger birefringences in SrTi(IO3)6·2H2O and SrSn(IO3)6 than that in (H3O)2Ti(IO3)6.
Theoretical study of the H/D isotope effect of CH4/CD4 adsorption on a Rh(111) surface using a combined plane wave and localized basis sets method
Authors: Sakagami Hiroki , Tachikawa Masanori , Ishimoto Takayoshi
Published: March 2021

Using our CPLB method, we elucidate that the adsorption distance and adsorption energy of CH4 on the Rh(111) surface are shorter and larger than those of CD4, which is in reasonable agreement with the corresponding H/D isotope trend in experiments.