bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Stimulus Intensity on Laryngeal Long Latency Responses in Awake Humans
Authors: Yamashita Toshiyuki , Nash Eric A. , Tanaka Yasumasa , Ludlow Christy L.
Published: February 2022

Percutaneous electrical stimulation applied to the internal branch of the superior laryngeal nerve (ISLN) results in two long latency laryngeal adductor responses in awake humans: an ipsilateral thyroarytenoid (TA) R1 muscle response at 16 ms, and later bilateral TA R2 muscle responses at 60 ms. The purpose of this study was to determine whether a functional relationship existed between the R1 and R2 responses by gradually increasing the level of electrical stimulation from threshold to supramaximal levels. R1 amplitude increased linearly with stimulation intensity in 9 of the 11 subjects, whereas R2 only had a positive linear relationship in 3 subjects and a negative relationship with stimulation intensity in 1 subject. Significant negative relationships were found between response latency and stimulation intensify in 3 subjects for the R1 responses and 3 other subjects for the R2 responses. Overall, R1 amplitudes increased systematically, whereas R2 responses varied in latency and amplitude with increasing stimulus Intensity. Neither the latencies nor the amplitudes of the two responses were related after adjusting for stimulation intensity within subjects by using partial correlation coefficients. The R1 and R2 responses were functionally unrelated and most likely have different neural components.
The Federated Entities in Environmental Treaties (FEET) Dataset: Questioning Conventional Wisdom on Green Paradiplomacy
Authors: Morin Jean-Frédéric , Fournier Véronique , Paquin Stéphane
Published: February 2022

The existing literature underestimates the contribution of federated entities to international environmental agreements. This research note introduces a novel dataset on the role of federated entities in 2,077 environmental agreements. We demonstrate the value of this dataset by revisiting unexamined assumptions that stem from the literature. According to conventional wisdom, (1) federated entities’ participation in environmental agreements is a recent phenomenon, (2) this phenomenon is led by federated entities in Western democracies, (3) it has accelerated as a response to the climate crisis and (4) it is driven by the same movement that favours the participation of diverse stakeholders. This research note questions these preconceived ideas and illustrates how the new dataset sheds light on the role of federated entities in environmental governance.
Intubation with a Tritube to avoid peri-operative tracheostomy in open airway surgery
Authors: Leow T Y S , Van der Wal R A B , Marres H A M , Honings J
Published: February 2022

Background

This paper reports a case of chondrosarcoma deriving from the left arytenoid cartilage that was resected via an anterior laryngofissure using the Tritube in situ, thus eliminating the need for a (temporary) tracheostomy.

Case report

A 49-year-old male with a chondrosarcoma deriving from the left arytenoid was treated with local resection of the tumour through an anterior laryngofissure. The intralaryngeal lumen was too small for a normal endotracheal tube. Using the Tritube (outer diameter, 4.4 mm), the patient could be intubated and ventilated adequately during the procedure. The Tritube did not obstruct the surgical view during the procedure.

Conclusion

The Tritube can be used for intubation and ventilation even in patients with a very narrow airway lumen, and does not obstruct the field of view during open laryngeal surgery, thereby avoiding the need for peri-operative tracheostomy.
Can epigenetics shine a light on the biological pathways underlying major mental disorders?
Authors: Alameda Luis , Trotta Giulia , Quigley Harriet , Rodriguez Victoria , Gadelrab Romayne , Dwir Daniella , Dempster Emma , Wong Chloe C. Y. , Forti Marta Di
Published: February 2022

A significant proportion of the global burden of disease can be attributed to mental illness. Despite important advances in identifying risk factors for mental health conditions, the biological processing underlying causal pathways to disease onset remain poorly understood. This represents a limitation to implement effective prevention and the development of novel pharmacological treatments. Epigenetic mechanisms have emerged as mediators of environmental and genetic risk factors which might play a role in disease onset, including childhood adversity (CA) and cannabis use (CU). Particularly, human research exploring DNA methylation has provided new and promising insights into the role of biological pathways implicated in the aetio-pathogenesis of psychiatric conditions, including: monoaminergic (Serotonin and Dopamine), GABAergic, glutamatergic, neurogenesis, inflammatory and immune response and oxidative stress. While these epigenetic changes have been often studied as disease-specific, similarly to the investigation of environmental risk factors, they are often transdiagnostic. Therefore, we aim to review the existing literature on DNA methylation from human studies of psychiatric diseases (i) to identify epigenetic modifications mapping onto biological pathways either transdiagnostically or specifically related to psychiatric diseases such as Eating Disorders, Post-traumatic Stress Disorder, Bipolar and Psychotic Disorder, Depression, Autism Spectrum Disorder and Anxiety Disorder, and (ii) to investigate a convergence between some of these epigenetic modifications and the exposure to known risk factors for psychiatric disorders such as CA and CU, as well as to other epigenetic confounders in psychiatry research.
The 2021 Congress of the International Society for Twin Studies: Twin Research at the Cutting Edge/Twin Research: Maternal Bonding with Twins; Twins with Peters Anomaly; Selective Termination in Dichorionic Twin Pairs; Neuropsychological Function in Twins with Neurofibromatosis/News Reports: World’s Most Premature Survivor — A Twin; Twins Confuse Giants’ Baseball Fans; Malaysian Twins Switched at Birth; ‘Biracial’ Twins
Authors: Segal Nancy L. , Pratt-Thompson Elizabeth
Published: February 2022

Selected highlights from the 2021 Congress of the International Society for Twin Studies are reviewed. The perspectives of a new graduate student member to the society are also included. Timely research covering issues related to maternal bonding with twins, twins with Peters anomaly, selective termination in dichorionic twin pairs and neuropsychological functioning in twins with neurofibromatosis is reviewed. The final part of this article includes interesting and informative media reports related to the world’s most premature survivor who is a twin, identical male baseball players, Malaysian twins switched at birth and a pair of the so-called ‘biracial’ twins.
Review: Induced Seismicity During Geoenergy Development—A Hydromechanical Perspective
Authors: Ge Shemin , Saar Martin O.
Published: February 2022

The basic triggering mechanism underlying induced seismicity traces back to the mid‐1960s that relied on the process of pore‐fluid pressure diffusion. The last decade has experienced a renaissance of induced seismicity research and data proliferation. An unprecedent opportunity is presented to us to synthesize the robust growth in knowledge. The objective of this article is to provide a concise review of the triggering mechanisms of induced earthquakes with a focus on hydro‐mechanical processes. Four mechanisms are reviewed: pore‐fluid pressure diffusion, poroelastic stress, Coulomb static stress transfer, and aseismic slip. For each, an introduction of the concept is presented, followed by case studies. Diving into these mechanisms sheds light on several outstanding questions. For example, why did some earthquakes occur far from fluid injection or after injection stopped? Our review converges on the following conclusions: (a) Pore‐fluid pressure diffusion remains a basic mechanism for initiating inducing seismicity in the near‐field. (b) Poroelastic stresses and aseismic slip play an important role in inducing seismicity in regions beyond the influence of pore‐fluid pressure diffusion. (c) Coulomb static stress transfer from earlier seismicity is shown to be a viable mechanism for increasing stresses on mainshock faults. (d) Multiple mechanisms have operated concurrently or consecutively at most induced seismicity sites. (e) Carbon dioxide injection is succeeding without inducing earthquakes and much can be learned from its success. Future research opportunities exist in deepening the understanding of physical and chemical processes in the nexus of geoenergy development and fluid motion in the Earth’s crust.
Forest Fires Could Boost Western U.S. Water Supplies
Authors: Schmidt Jennifer
Published: February 2022

Streamflow in the West has been below average since the early 2000s, but a new analysis shows that streams aren’t as dry as expected.
Highly integrated watch for noninvasive continual glucose monitoring
Authors: Chang Tianrui , Li Hu , Zhang Nianrong , Jiang Xinran , Yu Xinge , Yang Qingde , Jin Zhiyuan , Meng Hua , Chang Lingqian
Published: February 2022

This article reports a highly integrated watch for noninvasive continual blood glucose monitoring. The watch employs a Nafion-coated flexible electrochemical sensor patch fixed on the watchband to obtain interstitial fluid (ISF) transdermally at the wrist. This reverse iontophoresis-based extraction method eliminates the pain and inconvenience that traditional fingerstick blood tests pose in diabetic patients’ lives, making continual blood glucose monitoring practical and easy. All electronic modules, including a rechargeable power source and other modules for signal processing and wireless transmission, are integrated onto a watch face-sized printed circuit board (PCB), enabling comfortable wearing of this continual glucose monitor. Real-time blood glucose levels are displayed on the LED screen of the watch and can also be checked with the smartphone user interface. With 23 volunteers, the watch demonstrated 84.34% clinical accuracy in the Clarke error grid analysis (zones A + B). In the near future, commercial products could be developed based on this lab-made prototype to provide the public with noninvasive continual glucose monitoring.
Enterobacteria impair host p53 tumor suppressor activity through mRNA destabilization
Authors: Aschtgen Marie-Stéphanie , Fragkoulis Konstantinos , Sanz Gema , Normark Staffan , Selivanova Galina , Henriques-Normark Birgitta , Peuget Sylvain
Published: February 2022

Increasing evidence highlights the role of bacteria in the physiopathology of cancer. However, the underlying molecular mechanisms remains poorly understood. Several cancer-associated bacteria have been shown to produce toxins which interfere with the host defense against tumorigenesis. Here, we show that lipopolysaccharides from Klebsiella pneumoniae and other Enterobacteria strongly inhibit the host tumor suppressor p53 pathway through a novel mechanism of p53 regulation. We found that lipopolysaccharides destabilize TP53 mRNA through a TLR4-NF-κB-mediated inhibition of the RNA-binding factor Wig-1. Importantly, we show that K. pneumoniae disables two major tumor barriers, oncogene-induced DNA damage signaling and senescence, by impairing p53 transcriptional activity upon DNA damage and oncogenic stress. Furthermore, we found an inverse correlation between the levels of TLR4 and p53 mutation in colorectal tumors. Hence, our data suggest that the repression of p53 by Enterobacteria via TLR4 alleviates the selection pressure for p53 oncogenic mutations and shapes the genomic evolution of cancer.
Targeting polarized phenotype of microglia via IL6/JAK2/STAT3 signaling to reduce NSCLC brain metastasis
Authors: Jin Yu , Kang Yalin , Wang Minghuan , Wu Bili , Su Beibei , Yin Han , Tang Yang , Li Qianxia , Wei Wenjie , Mei Qi , Hu Guangyuan , Lukacs-Kornek Veronika , Li Jian , Wu Kongming , Yuan Xianglin , Wang Wei
Published: February 2022

Tumor-associated macrophages have emerged as crucial factors for metastases. Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis (BM). However, the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung cancer (NSCLC) remains elusive. Here, we purified cell lines with brain-metastatic tropism and employed a co-culture system to reveal their communication with microglia. By single-cell RNA-sequencing and transcriptome difference analysis, we identified IL6 as the key regulator in brain-metastatic cells (A549-F3) to induce anti-inflammatory microglia via JAK2/STAT3 signaling, which in turn promoted the colonization process in metastatic A549-F3 cells. In our clinical samples, patients with higher levels of IL6 in serum showed higher propensity for brain metastasis. Additionally, the TCGA (The Cancer Genome Atlas) data revealed that NSCLC patients with a lower level of IL6 had a longer overall survival time compared to those with a higher level of IL6. Overall, our data indicate that the targeting of IL6/JAK2/STAT3 signaling in activated microglia may be a promising new approach for inhibiting brain metastasis in NSCLC patients.
Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration
Authors: Wei Hongpu , Cui Jinjie , Lin Kaili , Xie Jing , Wang Xudong
Published: February 2022

Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem, researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific pH reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration. Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.
Is preventable sight loss truly preventable? An exploration of a public health indicator for sight loss due to age-related macular degeneration in England
Authors: Brown Kelsey , Bunce Catey , Onabanjo Oluwaseun , Strong Stacey A. , Patel Praveen J.
Published: February 2022

Background

Age-related macular degeneration accounts for the majority of severe sight impairment and sight impairment registration and certifications in adults in the UK [1, 2]. Whilst these treatments are effective in arresting nAMD progression, there is currently no treatment for GA [1, 3, 4].

Methods

This paper provides an update to the data collected by Bunce et al. [3] and details the number of people certified together with incidence rates for the various types of AMD by: sex, sight impairment status, and for all ages using the 2016/2017 and 2017/2018 CVI due to AMD data for England from the Moorfields Eye Hospital, supplemented with 2017–2018 PHOF indicator 4.12i/E12a data. The study population includes individuals of all ages in England who were newly certified with visual impairment due to AMD.

Results

Between 2016 and 2017, CVIs due to AMD totalled to 11,215; between 2017 and 2018, CVIs due to AMD totalled to 10,914. The PHOF indicator 4.12i/E12a assessed showed that overall rates of AMD certifications have steadily declined in England from 131.5 per 100,000 in 2010/2011 to 106.7 per 100,000 in 2017/2018.

Conclusion

As treatment is available for nAMD, a reduction in nAMD certifications could be expected; however, growth of the elderly population in England combined with there currently being no treatment available for GA means AMD certification rates should be increasing. Therefore, it is postulated that not all cases of AMD are being certified and registered with some likely going undiagnosed.
High-resolution analysis for urinary DNA jagged ends
Authors: Xie Tingting , Wang Guangya , Ding Spencer C. , Lee Wing-Shan , Cheng Suk Hang , Chan Rebecca W. Y. , Zhou Ze , Ma Mary-Jane L. , Han Diana S. C. , Teoh Jeremy Y. C. , Lam W. K. Jacky , Jiang Peiyong , Chiu Rossa W. K. , Chan K. C. Allen , Lo Y. M. Dennis
Published: February 2022

Single-stranded ends of double-stranded DNA (jagged ends) are more abundant in urinary DNA than in plasma DNA. However, the lengths of jagged ends in urinary DNA remained undetermined, as a previous method used for urinary DNA jagged end sequencing analysis (Jag-seq) relied on unmethylation at CpG sites, limiting the resolution. Here, we performed high-resolution Jag-seq analysis using methylation at non-CpG cytosine sites, allowing determination of exact length of jagged ends. The urinary DNA bore longer jagged ends (~26-nt) than plasma DNA (~17-nt). The jagged end length distribution displayed 10-nt periodicities in urinary DNA, which were much less observable in plasma DNA. Amplitude of the 10-nt periodicities increased in patients with renal cell carcinoma. Heparin treatment of urine diminished the 10-nt periodicities. The urinary DNA jagged ends often extended into nucleosomal cores, suggesting potential interactions with histones. This study has thus advanced our knowledge of jagged ends in urine DNA.
Deep neural network prediction of genome-wide transcriptome signatures – beyond the Black-box
Authors: Magnusson Rasmus , Tegnér Jesper N. , Gustafsson Mika
Published: February 2022

Prediction algorithms for protein or gene structures, including transcription factor binding from sequence information, have been transformative in understanding gene regulation. Here we ask whether human transcriptomic profiles can be predicted solely from the expression of transcription factors (TFs). We find that the expression of 1600 TFs can explain >95% of the variance in 25,000 genes. Using the light-up technique to inspect the trained NN, we find an over-representation of known TF-gene regulations. Furthermore, the learned prediction network has a hierarchical organization. A smaller set of around 125 core TFs could explain close to 80% of the variance. Interestingly, reducing the number of TFs below 500 induces a rapid decline in prediction performance. Next, we evaluated the prediction model using transcriptional data from 22 human diseases. The TFs were sufficient to predict the dysregulation of the target genes (rho = 0.61, P < 10−216). By inspecting the model, key causative TFs could be extracted for subsequent validation using disease-associated genetic variants. We demonstrate a methodology for constructing an interpretable neural network predictor, where analyses of the predictors identified key TFs that were inducing transcriptional changes during disease.
An adjuvanted subunit SARS-CoV-2 spike protein vaccine provides protection against Covid-19 infection and transmission
Authors: Tabynov Kairat , Turebekov Nurkeldi , Babayeva Meruert , Fomin Gleb , Yerubayev Toktassyn , Yespolov Tlektes , Li Lei , Renukaradhya Gourapura J. , Petrovsky Nikolai , Tabynov Kaissar
Published: February 2022

Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals (n = 2/group) placed in the same cage as challenged animals (n = 6/group). The results contrasted with only weak protection seen with a monomeric spike receptor-binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging results warrant the ongoing development of this COVID-19 vaccine candidate.
Durability and expansion of neutralizing antibody breadth following Ad26.COV2.S vaccination of mice
Authors: Mahrokhian Shant H. , Tostanoski Lisa H. , Jacob-Dolan Catherine , Zahn Roland C. , Wegmann Frank , McMahan Katherine , Yu Jingyou , Gebre Makda S. , Bondzie Esther A. , Wan Huahua , Powers Olivia , Ye Tianyi , Barrett Julia , Schuitemaker Hanneke , Barouch Dan H.
Published: February 2022

Emerging SARS-CoV-2 variants with the potential to escape binding and neutralizing antibody responses pose a threat to vaccine efficacy. We recently reported expansion of broadly neutralizing activity of vaccine-elicited antibodies in humans 8 months following a single immunization with Ad26.COV2.S. Here, we assessed the 15-month durability of antibody responses and their neutralizing capacity to B.1.617.2 (delta) and B.1.351 (beta) variants following a single immunization of Ad26.COV2.S in mice. We report the persistence of binding and neutralizing antibody titers following immunization with a concomitant increase in neutralizing antibody breadth to delta and beta variants over time. Evaluation of bone marrow and spleen at 15 months postimmunization revealed that Ad26.COV2.S-immunized mice tissues contained spike-specific antibody-secreting cells. We conclude that immunization with Ad26.COV2.S elicits a robust immune response against SARS-CoV-2 spike, which expands over time to neutralize delta and beta variants more robustly, and seeds bone marrow and spleen with long-lived spike-specific antibody-secreting cells. These data extend previous findings in humans and support the use of a mouse model as a potential tool to further explore the dynamics of the humoral immune response following vaccination with Ad26.COV2.S.
Hyperbolic shear polaritons in low-symmetry crystals
Authors: Passler Nikolai C. , Ni Xiang , Hu Guangwei , Matson Joseph R. , Carini Giulia , Wolf Martin , Schubert Mathias , Alù Andrea , Caldwell Joshua D. , Folland Thomas G. , Paarmann Alexander
Published: February 2022

The lattice symmetry of a crystal is one of the most important factors in determining its physical properties. Particularly, low-symmetry crystals offer powerful opportunities to control light propagation, polarization and phase1–4. Materials featuring extreme optical anisotropy can support a hyperbolic response, enabling coupled light–matter interactions, also known as polaritons, with highly directional propagation and compression of light to deeply sub-wavelength scales5. Here we show that monoclinic crystals can support hyperbolic shear polaritons, a new polariton class arising in the mid-infrared to far-infrared due to shear phenomena in the dielectric response. This feature emerges in materials in which the dielectric tensor cannot be diagonalized, that is, in low-symmetry monoclinic and triclinic crystals in which several oscillators with non-orthogonal relative orientations contribute to the optical response6,7. Hyperbolic shear polaritons complement previous observations of hyperbolic phonon polaritons in orthorhombic1,3,4 and hexagonal8,9 crystal systems, unveiling new features, such as the continuous evolution of their propagation direction with frequency, tilted wavefronts and asymmetric responses. The interplay between diagonal loss and off-diagonal shear phenomena in the dielectric response of these materials has implications for new forms of non-Hermitian and topological photonic states. We anticipate that our results will motivate new directions for polariton physics in low-symmetry materials, which include geological minerals10, many common oxides11 and organic crystals12, greatly expanding the material base and extending design opportunities for compact photonic devices.
TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A
Authors: Ma X. Rosa , Prudencio Mercedes , Koike Yuka , Vatsavayai Sarat C. , Kim Garam , Harbinski Fred , Briner Adam , Rodriguez Caitlin M. , Guo Caiwei , Akiyama Tetsuya , Schmidt H. Broder , Cummings Beryl B. , Wyatt David W. , Kurylo Katherine , Miller Georgiana , Mekhoubad Shila , Sallee Nathan , Mekonnen Gemechu , Ganser Laura , Rubien Jack D. , Jansen-West Karen , Cook Casey N. , Pickles Sarah , Oskarsson Björn , Graff-Radford Neill R. , Boeve Bradley F. , Knopman David S. , Petersen Ronald C. , Dickson Dennis W. , Shorter James , Myong Sua , Green Eric M. , Seeley William W. , Petrucelli Leonard , Gitler Aaron D.
Published: February 2022

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord1. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing2–4. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies5,6, but how those variants increase risk for disease is unknown. Here we show that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harbouring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function.
A biophysical account of multiplication by a single neuron
Authors: Groschner Lukas N. , Malis Jonatan G. , Zuidinga Birte , Borst Alexander
Published: February 2022

Nonlinear, multiplication-like operations carried out by individual nerve cells greatly enhance the computational power of a neural system1–3, but our understanding of their biophysical implementation is scant. Here we pursue this problem in the Drosophila melanogaster ON motion vision circuit4,5, in which we record the membrane potentials of direction-selective T4 neurons and of their columnar input elements6,7 in response to visual and pharmacological stimuli in vivo. Our electrophysiological measurements and conductance-based simulations provide evidence for a passive supralinear interaction between two distinct types of synapse on T4 dendrites. We show that this multiplication-like nonlinearity arises from the coincidence of cholinergic excitation and release from glutamatergic inhibition. The latter depends on the expression of the glutamate-gated chloride channel GluClα8,9 in T4 neurons, which sharpens the directional tuning of the cells and shapes the optomotor behaviour of the animals. Interacting pairs of shunting inhibitory and excitatory synapses have long been postulated as an analogue approximation of a multiplication, which is integral to theories of motion detection10,11, sound localization12 and sensorimotor control13.
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
Authors: Brown Anna-Leigh , Wilkins Oscar G. , Keuss Matthew J. , Hill Sarah E. , Zanovello Matteo , Lee Weaverly Colleen , Bampton Alexander , Lee Flora C. Y. , Masino Laura , Qi Yue A. , Bryce-Smith Sam , Gatt Ariana , Hallegger Martina , Fagegaltier Delphine , Phatnani Hemali ,   NYGC ALS Consortium, Phatnani Hemali , Kwan Justin , Sareen Dhruv , Broach James R. , Simmons Zachary , Arcila-Londono Ximena , Lee Edward B. , Van Deerlin Vivianna M. , Shneider Neil A. , Fraenkel Ernest , Ostrow Lyle W. , Baas Frank , Zaitlen Noah , Berry James D. , Malaspina Andrea , Fratta Pietro , Cox Gregory A. , Thompson Leslie M. , Finkbeiner Steve , Dardiotis Efthimios , Miller Timothy M. , Chandran Siddharthan , Pal Suvankar , Hornstein Eran , MacGowan Daniel J. , Heiman-Patterson Terry , Hammell Molly G. , Patsopoulos Nikolaos. A. , Butovsky Oleg , Dubnau Joshua , Nath Avindra , Bowser Robert , Harms Matthew , Aronica Eleonora , Poss Mary , Phillips-Cremins Jennifer , Crary John , Atassi Nazem , Lange Dale J. , Adams Darius J. , Stefanis Leonidas , Gotkine Marc , Baloh Robert H. , Babu Suma , Raj Towfique , Paganoni Sabrina , Shalem Ophir , Smith Colin , Zhang Bin , Harris Brent , Broce Iris , Drory Vivian , Ravits John , McMillan Corey , Menon Vilas , Wu Lani , Altschuler Steven , Lerner Yossef , Sattler Rita , Van Keuren-Jensen Kendall , Rozenblatt-Rosen Orit , Lindblad-Toh Kerstin , Nicholson Katharine , Gregersen Peter , Lee Jeong-Ho , Koks Sulev , Muljo Stephen , Newcombe Jia , Gustavsson Emil K. , Seddighi Sahba , Reyes Joel F. , Coon Steven L. , Ramos Daniel , Schiavo Giampietro , Fisher Elizabeth M. C. , Raj Towfique , Secrier Maria , Lashley Tammaryn , Ule Jernej , Buratti Emanuele , Humphrey Jack , Ward Michael E. , Fratta Pietro
Published: February 2022

Variants of UNC13A, a critical gene for synapse function, increase the risk of amyotrophic lateral sclerosis and frontotemporal dementia1–3, two related neurodegenerative diseases defined by mislocalization of the RNA-binding protein TDP-434,5. Here we show that TDP-43 depletion induces robust inclusion of a cryptic exon in UNC13A, resulting in nonsense-mediated decay and loss of UNC13A protein. Two common intronic UNC13A polymorphisms strongly associated with amyotrophic lateral sclerosis and frontotemporal dementia risk overlap with TDP-43 binding sites. These polymorphisms potentiate cryptic exon inclusion, both in cultured cells and in brains and spinal cords from patients with these conditions. Our findings, which demonstrate a genetic link between loss of nuclear TDP-43 function and disease, reveal the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. They further provide a promising therapeutic target for TDP-43 proteinopathies.
Effective drug combinations in breast, colon and pancreatic cancer cells
Authors: Jaaks Patricia , Coker Elizabeth A. , Vis Daniel J. , Edwards Olivia , Carpenter Emma F. , Leto Simonetta M. , Dwane Lisa , Sassi Francesco , Lightfoot Howard , Barthorpe Syd , van der Meer Dieudonne , Yang Wanjuan , Beck Alexandra , Mironenko Tatiana , Hall Caitlin , Hall James , Mali Iman , Richardson Laura , Tolley Charlotte , Morris James , Thomas Frances , Lleshi Ermira , Aben Nanne , Benes Cyril H. , Bertotti Andrea , Trusolino Livio , Wessels Lodewyk , Garnett Mathew J.
Published: February 2022

Combinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS–TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
The bacterial toxin colibactin triggers prophage induction
Authors: Silpe Justin E. , Wong Joel W. H. , Owen Siân V. , Baym Michael , Balskus Emily P.
Published: February 2022

Colibactin is a chemically unstable small-molecule genotoxin that is produced by several different bacteria, including members of the human gut microbiome1,2. Although the biological activity of colibactin has been extensively investigated in mammalian systems3, little is known about its effects on other microorganisms. Here we show that colibactin targets bacteria that contain prophages, and induces lytic development through the bacterial SOS response. DNA, added exogenously, protects bacteria from colibactin, as does expressing a colibactin resistance protein (ClbS) in non-colibactin-producing cells. The prophage-inducing effects that we observe apply broadly across different phage–bacteria systems and in complex communities. Finally, we identify bacteria that have colibactin resistance genes but lack colibactin biosynthetic genes. Many of these bacteria are infected with predicted prophages, and we show that the expression of their ClbS homologues provides immunity from colibactin-triggered induction. Our study reveals a mechanism by which colibactin production could affect microbiomes and highlights a role for microbial natural products in influencing population-level events such as phage outbreaks.
Lowering the setting value of the esophageal endoscopic submucosal dissection device enabled tissue damage control in vitro porcine model
Authors: Yamaguchi Yukiko , Uesato Masaya , Yonemoto Shohei , Maruyama Tetsuro , Urahama Ryuma , Suito Hiroshi , Kishimoto Takashi , Shiko Yuki , Ozawa Yoshihito , Kawasaki Yohei , Matsubara Hisahiro
Published: February 2022

One of the complications of esophageal endoscopic submucosal dissection (ESD) is postoperative stricture formation. Stenosis formation is associated with inflammation and fibrosis in the healing process. We hypothesized that the degree of thermal damage caused by the device is related to stricture formation. We aimed to reveal the relationship between thermal damage and setting value of the device. We energized a resected porcine esophagus using the ESD device (Flush Knife 1.5). We performed 10 energization points for 1 s, 3 s, and 5 s at four setting values of the device. We measured the amount of current flowing to the conducted points and the temperature and evaluated the effects of thermal damage pathologically. As results, the mean highest temperatures for 1 s were I (SWIFT Effect3 Wat20): 61.19 °C, II (SWIFT Effect3 Wat30): 77.28 °C, III (SWIFT Effect4 Wat20): 94.50 °C, and IV (SWIFT Effect4 Wat30): 94.29 °C. The mean heat denaturation areas were I: 0.84 mm2, II: 1.00 mm2, III: 1.91 mm2, and IV: 1.54 mm2. The mean highest temperature and mean heat denaturation area were significantly correlated (P < 0.001). In conclusion, Low-current ESD can suppress the actual temperature and thermal damage in the ESD wound.
Carex pulicaris abundance is positively associated with soil acidity, rainfall and floristic diversity in the eastern distribution range
Authors: Sotek Zofia , Stasińska Małgorzata , Malinowski Ryszard , Gamrat Renata , Gałczyńska Małgorzata , Kull Thea , Mochnacký Sergej , Grzejszczak Grzegorz , Paprota Dariusz , Kolarčik Vladislav
Published: February 2022

Carex pulicarisis considered an endangered species, and further losses are forecast under the influence of even moderate climate change. Local studies indicate that temporal declines inC. pulicarisabundance are positively correlated to decreases in precipitation and increases in air temperature. Determining ecological properties on larger scales than local ones can help develop effective protection programs for the species. We hypothesize that the local relationships observed betweenC. pulicarisabundance and precipitation, air temperature and soil properties will be confirmed in a spatially-oriented large-scale study performed in situ. Therefore, the present study takes a novel, large-scale integrated approach to (1) precisely characterize the ecological requirements ofC. pulicariswithin its eastern distribution range, and (2) determine the influence of its community type, soil properties and climatic conditions on its abundance. It was found thatC. pulicarisis not a dominant or codominant species in the studied phytocoenoses in the eastern distribution range. Five natural vegetation groups includingC. pulicaris, with significantly diverse species compositions, were resolved: well supported Estonian, Polish, Slovak and Radecz groups, and a weakly-supported Ambiguous group. The abundance ofC. pulicariswas found to be positively correlated with the composition of the geographically-diversified plant communities and atmospheric precipitation, and to be also negatively associated with latitude and soil pH. Although the species is adapted to a relatively wide range of soil types, such adaptation requires appropriate substrate moisture level and light conditions. The species prefers moist organic and mineral soils and grows on both acid and neutral medium, characterized by a narrow C:N ratio, with various amounts of digestible total P, Mg and N, and low levels of digestible K. Climate change, manifested by reduced rainfall, may be one of the most important predictors negatively affecting the occurrence ofC. pulicaris.
Gate reflectometry of single-electron box arrays using calibrated low temperature matching networks
Authors: Filmer Matthew J. , Huebner Matthew , Zirkle Thomas A. , Jehl Xavier , Sanquer Marc , Chisum Jonathan D. , Orlov Alexei O. , Snider Gregory L.
Published: February 2022

Sensitive dispersive readouts of single-electron devices (“gate reflectometry”) rely on one-port radio-frequency (RF) reflectometry to read out the state of the sensor. A standard practice in reflectometry measurements is to design an impedance transformer to match the impedance of the load to the characteristic impedance of the transmission line and thus obtain the best sensitivity and signal-to-noise ratio. This is particularly important for measuring large impedances, typical for dispersive readouts of single-electron devices because even a small mismatch will cause a strong signal degradation. When performing RF measurements, a calibration and error correction of the measurement apparatus must be performed in order to remove errors caused by unavoidable non-idealities of the measurement system. Lack of calibration makes optimizing a matching network difficult and ambiguous, and it also prevents a direct quantitative comparison between measurements taken of different devices or on different systems. We propose and demonstrate a simple straightforward method to design and optimize a pi matching network for readouts of devices with large impedance, $$Z \ge 1\hbox {M}\Omega$$

Z
≥
1
M
Ω

. It is based on a single low temperature calibrated measurement of an unadjusted network composed of a single L-section followed by a simple calculation to determine a value of the “balancing” capacitor needed to achieve matching conditions for a pi network. We demonstrate that the proposed calibration/error correction technique can be directly applied at low temperature using inexpensive calibration standards. Using proper modeling of the matching networks adjusted for low temperature operation the measurement system can be easily optimized to achieve the best conditions for energy transfer and targeted bandwidth, and can be used for quantitative measurements of the device impedance. In this work we use gate reflectometry to readout the signal generated by arrays of parallel-connected Al-AlOx single-electron boxes. Such arrays can be used as a fast nanoscale voltage sensor for scanning probe applications. We perform measurements of sensitivity and bandwidth for various settings of the matching network connected to arrays and obtain strong agreement with the simulations.
An analytical study of sound transmission loss of functionally graded sandwich cylindrical nanoshell integrated with piezoelectric layers
Authors: Thongchom Chanachai , Saffari Pouyan Roodgar , Refahati Nima , Saffari Peyman Roudgar , Pourbashash Hossein , Sirimontree Sayan , Keawsawasvong Suraparb
Published: February 2022

The multidisciplinary nature of piezoelectric (PZ) structures necessitates precise and efficient methods to express their behavior under different conditions. This article extends the general usage of PZ materials by introducing acoustic and fluid loading effects in a way that an unfilled multilayer cylindrical nanoshell with a functionally graded (FG) material core and PZ layers is subjected to preliminary external electric load, acoustic waves and external flow motion. As the properties of a functionally graded material changes along the shell thickness, a power law model is assumed to be governing such variations of desired characteristics. Evidently, this system includes different types of couplings and a comprehensive approach is required to describe the structural response. To this aim, the first-order shear deformation theory (FSDT) is used to define different displacement components. Next, the coupled size-dependent vibroacoustic equations are derived based on in conjunction with nonlocal strain gradient theory (NSGT) with the aid of Hamilton’s variational principle and fluid/structure compatibility conditions. NSGT is complemented with hardening and softening material effects which can greatly enhance the precision of results. It is expected to use the findings of this paper in the optimization of similar systems by selecting suitable FG index, incident angle of sound waves, flow Mach number, nonlocal and strain gradient parameters, starting electric potential and geometric features. One of the important findings of this study is that increasing the electric voltage can obtain better sound insulation at small frequencies, specially prior to the ring frequency.
Cascaded 3D UNet architecture for segmenting the COVID-19 infection from lung CT volume
Authors: L. Aswathy A. , S. Vinod Chandra S.
Published: February 2022

World Health Organization (WHO) declared COVID-19 (COronaVIrus Disease 2019) as pandemic on March 11, 2020. Ever since then, the virus is undergoing different mutations, with a high rate of dissemination. The diagnosis and prognosis of COVID-19 are critical in bringing the situation under control. COVID-19 virus replicates in the lungs after entering the upper respiratory system, causing pneumonia and mortality. Deep learning has a significant role in detecting infections from the Computed Tomography (CT). With the help of basic image processing techniques and deep learning, we have developed a two stage cascaded 3D UNet to segment the contaminated area from the lungs. The first 3D UNet extracts the lung parenchyma from the CT volume input after preprocessing and augmentation. Since the CT volume is small, we apply appropriate post-processing to the lung parenchyma and input these volumes into the second 3D UNet. The second 3D UNet extracts the infected 3D volumes. With this method, clinicians can input the complete CT volume of the patient and analyze the contaminated area without having to label the lung parenchyma for each new patient. For lung parenchyma segmentation, the proposed method obtained a sensitivity of 93.47%, specificity of 98.64%, an accuracy of 98.07%, and a dice score of 92.46%. We have achieved a sensitivity of 83.33%, a specificity of 99.84%, an accuracy of 99.20%, and a dice score of 82% for lung infection segmentation.
Large-scale epitaxy of two-dimensional van der Waals room-temperature ferromagnet Fe5GeTe2
Authors: Ribeiro Mário , Gentile Giulio , Marty Alain , Dosenovic Djordje , Okuno Hanako , Vergnaud Céline , Jacquot Jean-François , Jalabert Denis , Longo Danilo , Ohresser Philippe , Hallal Ali , Chshiev Mairbek , Boulle Olivier , Bonell Frédéric , Jamet Matthieu
Published: February 2022

In recent years, two-dimensional van der Waals materials have emerged as an important platform for the observation of long-range ferromagnetic order in atomically thin layers. Although heterostructures of such materials can be conceived to harness and couple a wide range of magneto-optical and magneto-electrical properties, technologically relevant applications require Curie temperatures at or above room temperature and the ability to grow films over large areas. Here we demonstrate the large-area growth of single-crystal ultrathin films of stoichiometric Fe5GeTe2 on an insulating substrate using molecular beam epitaxy. Magnetic measurements show the persistence of soft ferromagnetism up to room temperature in 12 nm-thick films, with a Curie temperature of 293 K, and a weak out-of-plane magnetocrystalline anisotropy. The ferromagnetic order is preserved in bilayer Fe5GeTe2, with Curie temperature decreasing to 229 K. Surface, chemical, and structural characterizations confirm the layer-by-layer growth, 5:1:2 Fe:Ge:Te stoichiometric elementary composition, and single-crystalline character of the films.
Fortilin interacts with TGF-β1 and prevents TGF-β receptor activation
Authors: Pinkaew Decha , Martinez-Hackert Erik , Jia Wei , King Matthew D. , Miao Fei , Enger Nicole R. , Silakit Runglawan , Ramana Kota , Chen Shi-You , Fujise Ken
Published: February 2022

Fortilin is a 172-amino acid multifunctional protein present in both intra- and extracellular spaces. Although fortilin binds and regulates various cellular proteins, the biological role of extracellular fortilin remains unknown. Here we report that fortilin specifically interacts with TGF-β1 and prevents it from activating the TGF-β1 signaling pathway. In a standard immunoprecipitation-western blot assay, fortilin co-immunoprecipitates TGF-β1 and its isoforms. The modified ELISA assay shows that TGF-β1 remains complexed with fortilin in human serum. Both bio-layer interferometry and surface plasmon resonance (SPR) reveal that fortilin directly bind TGF-β1. The SPR analysis also reveals that fortilin and the TGF-β receptor II (TGFβRII) compete for TGF-β1. Both luciferase and secreted alkaline phosphatase reporter assays show that fortilin prevents TGF-β1 from activating Smad3 binding to Smad-binding element. Fortilin inhibits the phosphorylation of Smad3 in both quantitative western blot assays and ELISA. Finally, fortilin inhibits TGFβ-1-induced differentiation of C3H10T1/2 mesenchymal progenitor cells to smooth muscle cells. A computer-assisted virtual docking reveals that fortilin occupies the pocket of TGF-β1 that is normally occupied by TGFβRII and that TGF-β1 can bind either fortilin or TGFβRII at any given time. These data support the role of extracellular fortilin as a negative regulator of the TGF-β1 signaling pathway.
Recent progress on hierarchical MoS2 nanostructures for electrochemical energy storage
Authors: Jia Yulong , Yin Guoliang , Lin Yinhe , Ma Ying
Published: February 2022

This review demonstrates the recent progress and future research prospect of hierarchical MoS2 nanostructures for electrochemical energy storage.
Facile and single-step entrapment of chloramphenicol in ZIF-8 and evaluation of its performance in killing infectious bacteria with high loading content and controlled release of the drug
Authors: Soltani Sajjad , Akhbari Kamran
Published: February 2022

CLN@ZIF-8 was prepared by trapping chloramphenicol during ZIF-8 synthesis with high DLC and DLE. It showed H2O2-sensitive controlled release with higher drug release under the simulated infectious conditions and short-time antibacterial activity.