bluuebunny/crossref_metadata_2025 huggingface dataset:
Scope and Limitations of the Palladium-Catalyzed Direct 1,2-Diheteroarylation of 1,2-Dihalobenzene Derivatives
Authors: Doucet Henri , Liu Linhao
Published: November 2022

The reactivity of 1,2-dihalobenzenes in palladium-catalyzed C–H bond functionalization is more difficult to control than that of 1,3- and 1,4-dihalobenzenes because of a possible Pd 1,4-migration during the second catalytic cycle. With C3-substituted heteroarenes this 1,4-palladium migration is not possible and the reaction allows the synthesis of a wide variety of functionalized 1,2-heteroarylated benzene derivatives in high yields. Conversely, only a few heteroarenes with a free C3 position, such as thiazoles, furans and imidazoles, allow the preparation of 1,2-heteroarylated benzenes. Despite these limitations, this one-pot procedure employing an easily available catalyst [Pd(OAc)2] and an inexpensive base (KOAc) provides a very simple method for the preparation of several 1,2-heteroarylated benzenes.
Auditory Mirror Therapy for Tinnitus: A Pilot Study
Authors: Linnman Clas
Published: November 2022

Background Tinnitus, the phantom perception of sound, shares many properties with phantom limb pain, in that both may arise as a consequence of sensory deprivation. Prediction errors in multisensory integration, such as induced with mirror box therapy in phantom pain, can reduce phantom percepts.

Purpose We evaluated if a device that swaps sound from the right pinna to the left ear canal, and from the left pinna to the right ear canal, can reduce tinnitus. We call this auditory mirror therapy (AMT).

Research Design Uncontrolled trial.

Study Sample Twenty subjects with chronic tinnitus.

Intervention An AMT device consisting of a modified ear defender device with microphones that swaps sounds from left pinna to the right ear canal and from the right pinna to the left ear canal. Participants used the device at home for 2 weeks.

Data Collection and Analysis Tinnitus Handicap Inventory (THI), Tinnitus Reaction Questionnaire, and visual analog scale ratings of symptoms were collected at baseline and posttreatment. Repeated measures t-test were performed, Bonferroni corrected for multiple comparisons.

Results There was a significant reduction in THI and in awareness of tinnitus after the AMT intervention.

Conclusion Exposing the audiovisual integration system to prediction errors can help retrain phantom percepts and reduce tinnitus handicap. Further studies on this concept are warranted.
Knee Arthroscopy Prior to Total Knee Arthroplasty: Temporal Relationship to Surgical Complications
Authors: Sax Oliver C. , Bains Sandeep S. , Chen Zhongming , Salib Christopher G. , Nace James , Delanois Ronald E.
Published: November 2022

Mechanical knee symptoms secondary to knee osteoarthritis (OA) may warrant knee arthroscopy (KA). Degenerative changes may progress and require a subsequent total knee arthroplasty (TKA). Recent studies have evaluated the timing of KA prior to TKA, associated a narrow interval with increased post-TKA complications. However, an updated analysis is required. We compared surgical outcomes in recipients of KA prior to TKA as stratified by four, time-dependent cohorts (< 12, 12 to 16, 16 to 20, and 20 to 24 weeks prior to TKA). We specifically compared: 90-day (1) manipulations under anesthesia (MUAs); (2) septic revisions at 90 days, 1 year, and 2 years; as well as (3) how various independent risk factors influenced the manipulations or revisions. We queried a national database for patients undergoing TKA. Patients who underwent KA with the following intervals: < 12 (n = 1,023), 12 to 16 (n = 816), 16 to 20 (n = 1,957), and 20 to 24 weeks (1,727) prior to TKA were compared with those patients who did not have a history of KA (n = 5,000). Bivariate analyses were utilized to assess 90 days through 2 years surgical outcomes. Afterwards, multivariate regression models were utilized to assess for independent risk factors. The unadjusted analyses showed an increase in MUA through 2 years among all the KA recipients (p < 0.001). Septic revisions and surgical site infections at all time points were not associated with any of the four arthroscopy time intervals (p > 0.476). The adjusted analyses showed an increased risk for 90-day MUA among all TKA cohorts (p < 0.001). Risk for septic revisions did not reach significance. Delaying TKA by 24 weeks in KA recipients was not associated with a decreased risk in septic revisions. However, there was an apparent risk of MUA at 90 days for all KA cohorts suggesting that waiting after KA before TKA makes no difference in MUA rates. These results update existing literature, may serve as an adjunct to current practice guidelines, and can contribute to shared decision making in the preoperative setting.
Chaotic synchronization of mutually coupled systems–arbitrary proportional linear relations
Authors: Kano Takumi , Umeno Ken
Published: November 2022

Considering a system combining two generalized Boolean transformations, we found that depending on the parameters, we can generate generalized synchronization such that the two chaotic orbits have arbitrary proportional linear relations. We rigorously determined its synchronization conditions by the explicit computing conditional Lyapunov exponent using the ergodic property and stable property of the Cauchy distribution. We found that a phenomenon similar to chaotic synchronization occurs even when the synchronization conditions are not strictly satisfied, which exhibits some degree of structural stability of chaotic synchronization. Our model can be further extended to systems with more degrees of freedom and, in the future, can be applied to reservoir computing.
Research, development and adoption for the north Australian beef cattle breeding industry: an analysis of needs and gaps
Authors: Bell Alan , Sangster Nicholas
Published: November 2022

This review seeks to analyse and prioritise needs and gaps in research and development (R&D) for the north Australian beef cattle breeding industry, and to advise on options to increase rates of adoption and successful implementation of this R&D. The material reviewed includes the peer-reviewed literature as well as industry reports and other relevant publications in three targeted areas of R&D deemed to be important by industry leaders and supporting scientists: (i) breeding herd management, (ii) feedbase management, and (iii) management of environmental sustainability. For breeding herd management, the need for uniform definition and consistent utilisation of appropriate productivity metrics is highlighted, with emphasis on assessment of maternal reproductive efficiency in terms of weaning (or branding) rates. Priority is given to the urgent need for reliable means of remotely assessing causes of neonatal calf mortality to enable the development and application of management interventions that improve calf survival rates. The highest priority for feedbase management is to increase producer awareness and willingness to adopt stocking rates that are appropriately matched to the long-term carrying capacity of native rangeland pastures that predominate in northern Australia. Other opportunities include increasing the use of perennial, tropically adapted legumes, where conditions permit, to improve soil fertility and nitrogen intake of cattle, and devising strategies to overcome widespread phosphorus deficiency through diagnosis and supplementation, especially in the wet season. In order to enhance environmental sustainability in the face of climate change, priorities include improving producer awareness and use of increasingly robust tools for predicting key weather events, as well as developing genetic strategies to increase heat tolerance of cattle and evaluating management interventions to mitigate heat stress. Conclusions drawn from these sections are summarised and used to make recommendations on priorities for increasing adoption of existing research-proven practices and technologies, and for further R&D on selected topics.
Systematic changes in circumpolar dust transport to the Subantarctic Pacific Ocean over the last two glacial cycles
Authors: Struve Torben , Longman Jack , Zander Martin , Lamy Frank , Winckler Gisela , Pahnke Katharina
Published: November 2022

The input of the soluble micronutrients iron (Fe) and/or manganese (Mn) by mineral dust stimulates net primary productivity in the Fe/Mn-deficient Southern Ocean. This mechanism is thought to increase carbon export, thus reducing atmospheric CO
2
during the Pleistocene glacial cycles. Yet, relatively little is known about changes in the sources and transport pathways of Southern Hemisphere dust over glacial cycles. Here, we use the geochemical fingerprint of the dust fraction in marine sediments and multiisotope mixture modeling to identify changes in dust transport to the South Pacific Subantarctic Zone (SAZ). Our data show that dust from South America dominated the South Pacific SAZ during most of the last 260,000 a with maximum contributions of up to ∼70% in the early part of the glacial cycles. The enhanced dust-Fe fluxes of the latter parts of the glacial cycles show increased contributions from Australia and New Zealand, but South American dust remains the dominant component. The systematic changes in dust provenance correspond with grain size variations, consistent with the circumpolar transport of dust by the westerly winds. Maximum contributions of dust from more proximal sources in Australia and New Zealand (up to ∼63%) paired with a finer dust grain size indicate reduced westerly wind speeds over the South Pacific SAZ during deglacial and peak interglacial intervals. These quantitative dust provenance changes provide source-specific dust-Fe fluxes in the South Pacific SAZ and show how their systematic changes in magnitude and timing influence the Southern Ocean dust-Fe feedback on glacial-interglacial to millennial time scales.
Internal variability and forcing influence model–satellite differences in the rate of tropical tropospheric warming
Authors: Po-Chedley Stephen , Fasullo John T. , Siler Nicholas , Labe Zachary M. , Barnes Elizabeth A. , Bonfils Céline J. W. , Santer Benjamin D.
Published: November 2022

Climate-model simulations exhibit approximately two times more tropical tropospheric warming than satellite observations since 1979. The causes of this difference are not fully understood and are poorly quantified. Here, we apply machine learning to relate the patterns of surface-temperature change to the forced and unforced components of tropical tropospheric warming. This approach allows us to disentangle the forced and unforced change in the model-simulated temperature of the midtroposphere (TMT). In applying the climate-model-trained machine-learning framework to observations, we estimate that external forcing has produced a tropical TMT trend of 0.25 ± 0.08 K⋅decade
−1
between 1979 and 2014, but internal variability has offset this warming by 0.07 ± 0.07 K⋅decade
−1
. Using the Community Earth System Model version 2 (CESM2) large ensemble, we also find that a discontinuity in the variability of prescribed biomass-burning aerosol emissions artificially enhances simulated tropical TMT change by 0.04 K⋅decade
−1
. The magnitude of this aerosol-forcing bias will vary across climate models, but since the latest generation of climate models all use the same emissions dataset, the bias may systematically enhance climate-model trends over the satellite era. Our results indicate that internal variability and forcing uncertainties largely explain differences in satellite-versus-model warming and are important considerations when evaluating climate models.
Evolution of inclusions in novel cryogenic high-Mn austenitic steel weld metal with cerium addition
Authors: Zhang Jinshuai , Li Guangqiang , Wang Honghong , Wan Xiangliang , Hu Mingfeng , Cao Yulong
Published: November 2022

Cerium (Ce) was effectively transitioned into the high-Mn austenitic steel weld metal under submerged arc welding by adding cerium dioxide and calcium silicon reducing agents into flux. The evolution behaviours of the composition, number density and size of inclusions in weld metal with different Ce contents were systematically investigated by thermodynamic calculation and experiments. The results show that the number density of inclusions increased and average size decreased with the increase of Ce content from 0 to 0.087 wt-%. Meanwhile, and the percentage of inclusions number with size less than 0.80 μm increased from 79.28% to 91.43%. The evolutionary process of inclusions was Al2O3 → Al11O18Ce → CeAlO3 → Ce2O3 → Ce2O2S with the increase of Ce content in the present weld metal. In particular, Ce-O-S-Al inclusion was extracted by in-situ sample preparation method, which proved its internal structure and evolution process. The complete formation model of Ce-Al-O-S system was also established.
Friend turned foe: TREM2 agonist in battles against tau
Authors: Carling Gillian , Luo Wenjie , Gan Li
Published: November 2022

In this important study, Jain et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220654) find that chronic TREM2 activation by AL002a antibody exacerbates the seeding and spread of pathological tau, enhances the disease-associated microglial signature, and increases neurite dystrophy in 5xFAD mice seeded with Alzheimer’s disease tau.
A direct approach for interfacing four-wire resistive sensors to microcontrollers
Authors: Reverter Ferran
Published: November 2022

In the field of direct sensor-to-microcontroller interface circuits, a novel proposal for four-wire connected resistive sensors is suggested and experimentally tested herein. The circuit relies on measuring six discharging times corresponding to six RC circuits, which include the sensor resistance and the parasitic resistance of the wires. The circuit has been applied to measure resistors emulating a Pt100 thermal sensor with different values of wire resistance. Experimental results show that the accuracy and linearity of the proposed circuit is not deteriorated while increasing the wire resistance, either by the mismatch between the wire resistances. The error, with respect to the case with null wire resistances, is lower than 45 mΩ, while the non-linearity error is lower than 0.05% full-scale span in the worst scenario under test.
Utilizing dual functions of LaPO4 to enhance the electrochemical performance of LiNi0.87Co0.09Al0.04O2 cathode material
Authors: Wu Yuxuan , Cheng Wendong , Hao Shuai , Li Lei , Ran Qiwen , Liu Ling , Ji Yuyao , Huo Jinsheng , Liu Xingquan
Published: November 2022

In this paper, via a facile wet coating method, the LaPO4 coating layer has been introduced onto the LiNi0.87Co0.09Al0.04O2 (NCA) surface while a small part of La3+ has also been doped on the surface to realize the dual functions modification of coating and doping. The morphology and structure of the samples were investigated by XRD, SEM and TEM measurements. The chemical compositions of the samples were analyzed via EDS and XPS data. The results showed that the coating of LaPO4 and the doping of La3+ were successfully achieved on the surface of NCA. Electrochemical tests indicate that the sample modified with 2 wt% LaPO4 (L2-NCA) possesses the best electrochemical performance. After 100 cycles, compared with the capacity retention rate of pristine NCA of 87.1%/74.2% at 0.5 C at 25 °C/60 °C, L2-NCA showed better cycling stability, and the capacity retention rate increased to 96.0%/85.1%, respectively. Besides, the rate performance of the modified samples at 1 C, 2 C and 5 C were also significantly improved. These satisfactory results reveal that the surface modification of LaPO4 provides a feasible scheme to uprate the performance of Ni-rich cathode materials.
Bending of a beam: an improvised instructional tool for the determination of density of a liquid
Authors: Bhattacharya Ahana , Chattopadhyay K N , Adhikary Chandan
Published: November 2022

An improvised instructional tool has been designed for the determination of density of a liquid by employing the elastic property of a metal bar. If a metal beam supported at two ends be loaded at the middle, then a depression is produced. These depressions are recorded by a travelling microscope for a known mass and a known volume of the test liquid whose density is to be measured, hanged as load at the middle of the bar. If the recorded depression is plotted against the respective mass and respective volume of the test liquid taken, a straight line is obtained in both the cases. The density of the test liquid is obtained from the slope of these two straight lines.
Effects of post metallization annealing on Al2O3 atomic layer deposition on n-GaN
Authors: Tadmor Liad , Brusaterra Enrico , Treidel Eldad Bahat , Brunner Frank , Bickel Nicole , Vandenbroucke Sofie S T , Detavernier Christophe , Würfl Joachim , Hilt Oliver
Published: November 2022

The chemical, physical and electrical properties and the robustness of post metallization annealed Al2O3 atomic layers deposited on n-type GaN are investigated in this work. Planar metal insulator capacitors are used to demonstrate a gate-first with following ohmic contacts formation at elevated temperature up to 600 °C process flow. X-ray photoelectron spectroscopy indicates that no new bonds in the Al2O3 layer are formed due to exposure to the elevated annealing temperature. X-ray diffraction measurements show no crystallization of the oxide layer. Atomic force microscopy shows signs of degradation of the sample annealed at 600 °C. Electrical measurements indicate that the elevated annealing temperature results in an increase of the oxide depletion and the deep depletion capacitances simultaneously, that results in a reduction of the flat band voltage to zero, which is explained by fixed oxide charges curing. A forward bias step stress capacitance measurement shows that the total number of induced trapped charges are not strongly affected by the elevated annealing temperatures. Interface trap density of states analysis shows the lowest trapping concentration for the capacitor annealed at 500 °C. Above this temperature, the interface trap density of states increases. When all results are taken into consideration, we have found that the process thermal budget allows for an overlap between the gate oxide post metallization annealing and the ohmic contact formation at 500 °C.
Design and defect study of Cs2AgBiBr6 double perovskite solar cell using suitable charge transport layers
Authors: Alkhammash Hend I , Mottakin M , Hossen Md Mosaddek , Akhtaruzzaman Md , Rashid Mohammad Junaebur
Published: November 2022

This work modelled and analysed perovskite solar cells based on Cs2AgBiBr6 with various electron transport layers and hole transport layers. The device structure is fluorine-doped tin oxide (FTO)/ZnO/Cs2AgBiBr6/NiO/Au. Power conversion efficiency (PCE) is practically saturated after the perovskite thickness of 700 nm. PCE declines from 21.88% to 1.58% when carrier lifetime decreases from 103 ns to 10−1 ns. Deep-level defects at mid-band gap energy of the perovskite layer can trap both carriers, allowing greater carrier recombination. Carrier capture cross-sectional area greatly impacts on cell performance. When subjected to high temperatures (T), the carrier mobility would diminish because carrier scattering increases cell resistance. That is why by raising T from 300 K to 400 K, the value of built-in potential (V
bi) decreases from 1.17 V to 0.98 V. Device shows maximum efficiency when FTO is used as the front electrode, and Au is used as a back electrode. The optimum device, made of FTO/ZnO/Cs2AgBiBr6/NiO/Au, provides V
oc = 1.29 V, J
sc = 20.69 mA cm−2, fill factor = 81.72%, and PCE = 21.88%.
A new symmetrical Z-shaped compliant linear actuator based on parasitic motion principle
Authors: Xie Yanlin , Li Yangmin , Cheung Benny Chifai
Published: November 2022

To meet the demand of designing piezoelectric actuators with long working stroke and high resolution, a new parasitic motion principle (PMP) linear actuator based on the symmetrical Z-shaped compliant mechanism was proposed in this paper. The mechanism design and the operation principle of the proposed linear actuator were elaborated. The theoretical model of the symmetrical Z shaped compliant mechanism deformation was established, and was verified by the simulation analysis. Experimental studies were conducted on a manufactured prototype to investigate the performances of the proposed linear actuator. The results indicate that a linear actuator with bi-directional motion can be achieved, which has a resolution of 106 nm in the forward direction and 84 nm in the reverse direction. Under the locking force of 0.8 N, the maximum speed of 270 µm s−1 was reached, when the amplitude and the frequency of the driving voltage were set to 60 V and 650 Hz. It is also noted that the proposed linear actuator can work with a loading capacity of 25 g. This study has provided an alternative way for the development of a PMP linear actuator with bi-directional motion.
Electric control of a phononic crystal constituted of Piezoelectric layers using Schottky diode
Authors: Hatoumva Massaï , Siryabe Emmanuel , Maréchal Pierre , Effa Joseph Yves , Betchewe Gambo
Published: November 2022

A one-dimensional piezoelectric phononic crystal (PPC) consisting of a periodic pattern made of two perfectly bonded materials: one active (piezoelectric), the other passive (elastic) and exhibiting a strong acoustic impedance contrast is studied. We are interested in the tunability of piezoelectric inclusions in order to control the propagation of ultrasonic waves in the MHz range from a nonlinear electrical component connected to the terminals of the piezoelectric elements. After modeling the dynamic resistance of the Schottky diode, based on the piezoelectricity equations, a one-dimensional analytical model is proposed to take into account the resistive impedance effect of this diode connected to the electrodes of the active plate. Thus, we have shown that the application of various electrical boundary conditions (EBCs) on the electrodes (open-circuit, short-circuit, connecting an electrical load) allows to change the effective properties of the piezoelectric plate in particular and those of the PPC in general. The dispersion of the waves is then electrically tuned and, depending on the applied EBCs, we have demonstrated numerically the possibility of opening Bragg or hybridization gaps in the PPC band structure.
Research on thermal actuation performance of twisted and coiled nylon artificial muscles based on yarn mechanics
Authors: Liu Guangdong , Zhang Yang , Di Jiangtao , Wu Zhengtian
Published: November 2022

Twisted and coiled artificial muscles (TCAMs) are recently introduced as novel structural actuators that offer outstanding performance. TCAMs consisting of nylon or other polymer fibers have the advantages of low cost, large stroke, and high power density, and can be used in the fields of robots and intelligent textiles. Manufacturing process and actuation conditions significantly affect the spiral structure of the fiber. Therefore, it is particularly important to conduct research on the manufacturing mechanics of TCAMs for their future development and applications. In this paper, a modeling based on yarn mechanics and the energy method is established for exploring the actuation performance of TCAMs. Firstly, we analyze the effects of the preparation and actuation conditions on the helical structure of TCAMs. The relationship between the spiral structure and the fiber tension is obtained. Then, we investigated the effects of preparation conditions, actuation load, and operating temperature on the tensile stroke of TCAMs. For silver-coated nylon fibers, the actuation performance of TCAMs decreased with the increase of suspension load. Finally, we verify the correctness of the model through experiments. Conversely, the present model can provide theoretical guidance for experimental research and optimized manufacturing of TCAMs.
Neural network-based motion modeling and control of water-actuated soft robotic fish
Authors: Chen Gang , Yang Xin , Xu Yidong , Lu Yuwang , Hu Huosheng
Published: November 2022

Soft actuator has broad application prospects due to its good compliance to different environments. However, its deformation is difficult to be described by the traditional method, so it is impossible to establish an accurate model of its motion, resulting in the difficulty of motion control of the software actuator. In this study, a soft robotic fish is designed, and a motion modeling method is proposed applying the neural network. The neural network-based motion model of the water-actuated soft robotic fish is constructed through neural network training with data collected by visual sensor. Further, a data set of control signals about the desired swing angle of robotic fish is established based on the motion model and stochastic algorithm, and the accurate motion control of the robot is implemented. The accuracy of the motion control method and the free swimming ability of the soft robotic fish using the control method in the water are analyzed quantitatively and qualitatively through the static and dynamic swing experiments of the robotic. This study provides a new idea for the motion modeling of soft actuators, which can effectively promote the development of modeling methods and theories of soft robots.
Small amplitude ion-acoustic solitary waves in a four-component magneto- rotating plasma with a modified Cairns-Tsallis distribution
Authors: Wang Hong , Du Jiulin , Guo Ran
Published: November 2022

The small amplitude ion-acoustic solitary waves in the magneto-rotating plasma consisting of cold fluid ions, hot positrons, and the two-temperature electrons (cold and hot electrons) are investigated when the electrons obey a modified Cairns-Tsallis distribution. By using the reductive perturbation method, we derive the Korteweg–de Vries equation and the modified Korteweg–de Vries equation and obtain the small amplitude ion-acoustic solitary wave solutions. The dependences of solitary wave solutions on the nonextensive q-parameter, the nonthermal α-parameter and the plasma physical quantities are analyzed numerically. We show the significant effects of the nonextensive q-parameter and the nonthermal α-parameter etc on the ion-acoustic solitary waves.
Autonomous three-dimensional oscillator with five terms: spiking oscillations generation mechanism, microcontroller implementation and controls
Authors: Ramakrishnan Balamurali , Kamdoum Tamba Victor , Mboupda Pone Justin Roger , Mbouna Ngueuteu Serge Gervais , Rajagopal Karthikeyan
Published: November 2022

This paper presents a report on the microcontroller implementation of an autonomous three-dimensional oscillator with five terms (ATDOFT) and performance analysis based on partial and total amplitude controls. ATDOFT displays periodic spiking behaviors, period-tripling bifurcation to chaos, chaotic spiking attractors, coexisting attractors and bistable attractors. ATDOFT is divided into two subsystems; namely the fast and slow subsystems to investigate the mechanism of the spiking dynamics. Relying on the stability analysis based on the fast subsystem with respect to the slow variable, it is shown that the spiking oscillations present in the ATDOFT arise from the system switching between the unstable state and the stable state of the lone equilibrium point of the fast subsystem. By inserting two controller parameters into the rate equations of the ATDOFT, total and partial amplitude controls are achieved. Finally, the dynamical behaviors found in ATDOFT are validated by the microcontroller implementation.
Inclusivity in cell biology: cultural identity and the power of authenticity
Authors: Langford George M.
Published: November 2022

I am deeply honored to be the recipient of the 2022 ASCB Public Service Award. In addition to my research on the cytoskeleton and molecular motors, I devoted a significant part of my professional career to issues pertaining to diversity, equity, and inclusion (DEI). Diversity of the scientific workforce is essential to accomplish the mission of discovery and innovation required to advance scientific knowledge and improve human health, especially the health of Black communities. This pressing need requires new approaches to address the problem of inclusivity in science. The Black Lives Matter movement and the murder of George Floyd were events that triggered people around the world to begin to reckon with structural racism and new approaches to dismantle it. It is through this momentary lens that I founded the PAIR-UP Imaging Science Program for Black Imaging Scientists. The purpose of PAIR-UP is to improve the professional work environment for Black imaging scientists at R1 institutions by building a self-reinforcing community of Black scientists across institutions committed to helping each other sustain a strong cultural identity. Reenforcing and sustaining a strong cultural identity has the potential to be transformational for the scientists participating in PAIR-UP.
Preprint Highlight: ERK-mediated curvature feedback regulates branching morphogenesis in lung epithelial tissue
Authors: Priya Rashmi
Published: November 2022

During development, cells operate in a complex geometrical environment. Geometry can inform morphogenesis by patterning mechanical and chemical signals. Yet, how this feedback occurs remains elusive. Using elegant imaging tools, mechanical perturbation, and modeling, the authors show that positive tissue curvature defines the site of highest ERK activity in lung epithelium. In turn, ERK dampens the curvature by promoting actin-mediated apical extension of cells. This negative feedback loop generates the branching pattern in developing lungs. These findings reinforce the notion that tissue geometry is necessary to comprehensively understand and recapitulate morphogenesis. This study will appeal to the broad cell and developmental biology community, as well as labs focusing on tissue engineering and in vitro organ models.
Preprint Highlight: ATR protects centromere identity by promoting DAXX association with PML nuclear bodies
Authors: Zhang Huaiying
Published: November 2022

ATR ( Ataxia telangiectasia and Rad3-related) is an essential kinase in the DNA damage response, but it also displays some DNA damage-independent roles in mitosis. By using an ATR inhibitor and genetic manipulations, this work shows that ATR phosphorylates the histone H3.3 chaperone DAXX to maintain its localization to PML (promyelocytic leukemia) nuclear bodies in interphase cells and thus ensures proper localization of centromere protein A (CENP-A) to centromeres. Reduced CENP-A localization on centromeres after ATR inhibition lasted through mitosis, resulting in chromosome segregation errors. This work adds to the understanding of ATR's role in genome stability independent of DNA damage response and may shed new light on how to reduce toxicity of ATR inhibitor-based cancer therapeutics.
Preprint Highlight: Detyrosination enrichment on microtubule subsets is established by the interplay between a stochastically acting enzyme and microtubule stability
Authors: Bonet-Ponce Luis
Published: November 2022

Microtubule detyrosination, the post-translational removal of a tyrosine residue on α-tubulin, marks a stable and rare subpopulation of microtubules. Vasohibin (VASH) is the main enzyme responsible for α-tubulin detyrosination and it binds to α-tubulin on polymerized microtubules. However, the dynamics underlying detyrosination remain unknown. The authors use quantitative super-resolution microscopy, single molecule tracking, and computational modeling to explore microtubule detyrosination. VASH engages with microtubules in a stochastic fashion and detyrosination depends on VASH concentration on single microtubules. As VASH accumulation requires microtubule stability, detyrosination occurs via a stabilization-detyrosination feedback mechanism. This work provides important and novel mechanistic insight into microtubule detyrosination and serves as an example for studying other microtubule post-translational modifications essential for cellular homeostasis.
Records of a Confident Man
Authors: Hampton Timothy
Published: November 2022

Bob Dylan’s prodigious creativity and transformation of popular song into literature raise new problems for writing about art. Neither traditional “poetry” criticism (which ignores sound and musical structure) nor traditional musicology (often indifferent to literary history) is adequate to the challenges posed by his work. Critics struggle to find a point of view from which to engage Dylan’s achievement. Through a critical account of four recent books, this essay points up both the limits and the resources of different approaches to this most mercurial of artists.
The altered production and property of saliva induced by ingesting fermented food ingredients affect the oral microbiome composition in mice
Authors: Kaibori Yuichiro , Yamashita Kazuhiko , Nagakubo Daisuke
Published: November 2022

Oral functions are diverse and critical to human health. Therefore, insufficient secretion or poor quality of saliva, which is secreted into the oral cavity and plays various roles, could have a crucial influence on the oral microenvironment and be associated with systemic disease development. Here, we investigated the effects of food ingredients on saliva quantity and quality, including fermented ones. Through the in vitro submandibular glands’ organ culture analyses, we found that “Yomo gyutto,” fermented Japanese mugwort (Artemisia princeps), altered the expression of aquaporin-5, a water channel protein. We also found that Yomo gyutto increased saliva volume, along with the amount of α-amylase in mice, and caused changes in the oral microbiome composition of mice. These results suggested that by ingesting Yomo gyutto, we could directly and effectively manipulate the quantity and quality of saliva secreted from the salivary glands, potentially altering the oral microbiome composition for individual health.
Enantioselective total syntheses of (S)-phosphonothrixin and unexpected cyclic derivative (S)-cyclic phosphonothrixin via enzymatic resolution
Authors: Nakamura Koki , Matsushima Yoshitaka
Published: November 2022

(S)-Phosphonothrixin is a phosphonate natural product produced by Saccharothrix sp. ST-888 that exhibits herbicidal activity. The previously reported asymmetric synthesis of (S)-phosphonothrixin is laborious and difficult to reproduce. In this study, we developed a scalable and concise enantioselective total synthesis of (S)-phosphonothrixin via two different synthetic routes by the enzymatic resolution of a known racemic epoxy alcohol. The second-generation synthesis was more efficient in terms of the overall yield (15%) and the number of steps (7) and afforded a unique cyclic phosphonate (phostone) as the product of the C–P bond formation reaction, which was converted to (S)-cyclic phosphonothrixin. Both (S)-phosphonothrixin and (S)-cyclic phosphonothrixin induced chlorosis in the plant Arabidopsis thaliana. However, (S)-cyclic phosphonothrixin exhibited lower activity than (S)-phosphonothrixin owing to its fixed conformation, as evidenced by a structure–activity relationship study. This study paves the way for the elucidation of the detailed mode of action of (S)-phosphonothrixin.
Editing a gateway for cell therapy across the blood–brain barrier
Authors: Achón Buil Beatriz , Tackenberg Christian , Rust Ruslan
Published: November 2022

Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cells into the stroke cavity but carry the risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, are minimally invasive, but most injected cells do not cross CNS barriers and become mechanically trapped in peripheral organs. Although the blood–brain barrier and the blood–CSF barrier tightly limit the entrance of cells and molecules into the brain parenchyma, immune cells can cross these barriers especially under pathological conditions, such as stroke. Deciphering the cell surface signature and the molecular mechanisms underlying this pathophysiological process holds promise for improving the targeted delivery of systemic injected cells to the injured brain. In this review, we describe experimental approaches that have already been developed in which (i) cells are either engineered to express cell surface proteins mimicking infiltrating immune cells; or (ii) cell grafts are preconditioned with hypoxia or incubated with pharmacological agents or cytokines. Modified cell grafts can be complemented with strategies to temporarily increase the permeability of the blood–brain barrier. Although these approaches could significantly enhance homing of stem cells into the injured brain, cell entrapment in off-target organs remains a non-negligible risk. Recent developments in safety-switch systems, which enable the precise elimination of transplanted cells on the administration of a drug, represent a promising strategy for selectively removing stem cells stuck in untargeted organs. In sum, the techniques described in this review hold great potential to substantially improve efficacy and safety of future cell therapies in stroke and may be relevant to other brain diseases.
Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status
Authors: van der Weijden Chris W J , Biondetti Emma , Gutmann Ingomar W , Dijkstra Hildebrand , McKerchar Rory , de Paula Faria Daniele , de Vries Erik F J , Meilof Jan F , Dierckx Rudi A J O , Prevost Valentin H , Rauscher Alexander
Published: November 2022

Myelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between the wraps. The measurement of damage to the myelin sheaths, the evaluation of the efficacy of therapies aiming to promote remyelination and monitoring the degree of brain maturation in children all require non-invasive quantitative myelin imaging methods. To date, various myelin imaging techniques have been developed. Five different MRI approaches can be distinguished based on their biophysical principles: (i) imaging of the water between the lipid bilayers directly (e.g. myelin water imaging); (ii) imaging the non-aqueous protons of the phospholipid bilayer directly with ultra-short echo-time techniques; (iii) indirect imaging of the macromolecular content (e.g. magnetization transfer; inhomogeneous magnetization transfer); (iv) mapping of the effects of the myelin sheath’s magnetic susceptibility on the MRI signal (e.g. quantitative susceptibility mapping); and (v) mapping of the effects of the myelin sheath on water diffusion. Myelin imaging with PET uses radioactive molecules with high affinity to specific myelin components, in particular myelin basic protein. This review aims to give an overview of the various myelin imaging techniques, their biophysical principles, image acquisition, data analysis and their validation status.
IL-2-based approaches to Treg enhancement
Authors: Harris Ffion , Berdugo Yoana Arroyo , Tree Timothy
Published: November 2022

Immune homeostasis is heavily dependent on the action of regulatory T cells (Tregs) which act to suppress the activation of many immune cell types including autoreactive conventional T cells. A body of evidence has shown that Tregs are intrinsically defective in many common autoimmune diseases, and gene polymorphisms which increase the susceptibility of autoimmune disease development have implicated the interleukin-2 (IL-2) signaling pathway as a key dysregulated mechanism. IL-2 is essential for Treg function and survival, and Tregs are highly sensitive to low levels of this cytokine in their environment. This review will revisit the rationale behind using low-dose IL-2 as a therapy to treat autoimmune diseases and evaluate the outcomes of trials to date. Furthermore, novel engineered IL-2 therapies with increased Treg specificity have shown promise in pre-clinical studies and human clinical trials for some agents have begun. Future studies will determine whether low-dose IL-2 or engineered IL-2 therapies can change the course of autoimmune and inflammatory diseases in patients.
Kidney function before and after acute kidney injury: a nationwide population-based cohort study
Authors: Jensen Simon Kok , Heide-Jørgensen Uffe , Vestergaard Søren Viborg , Gammelager Henrik , Birn Henrik , Nitsch Dorothea , Christiansen Christian Fynbo
Published: November 2022

Background

Acute kidney injury (AKI) is a common and serious condition defined by a rapid decline in kidney function. Data on changes in long-term kidney function following AKI are sparse and conflicting. Therefore, we examined the changes in estimated glomerular filtration rate (eGFR) from before to after AKI in a nationwide population-based setting.

Methods

Using Danish laboratory databases, we identified individuals with first-time AKI defined by an acute increase in plasma creatinine (pCr) during 2010 to 2017. Individuals with three or more outpatient pCr measurements before and after AKI were included and cohorts were stratified by baseline eGFR (≥/<60 mL/min/1.73 m2). Linear regression models were used to estimate and compare individual eGFR slopes and eGFR levels before and after AKI.

Results

Among individuals with a baseline eGFR ≥60 mL/min/1.73 m2 (n = 64 805), first-time AKI was associated with a median difference in eGFR level of −5.6 mL/min/1.73 m2 [interquartile range (IQR) −16.1 to 1.8] and a median difference in eGFR slope of −0.4 mL/min/1.73 m2/year (IQR −5.5 to 4.4). Correspondingly, among individuals with a baseline eGFR <60 mL/min/1.73 m2 (n = 33 267), first-time AKI was associated with a median difference in eGFR level of −2.2 mL/min/1.73 m2 (IQR −9.2 to 4.3) and a median difference in eGFR slope of 1.5 mL/min/1.73 m2/year (IQR −2.9 to 6.5).

Conclusion

Among individuals with first-time AKI surviving to have repeated outpatient pCr measurements, AKI was associated with changes in eGFR level and eGFR slope for which the magnitude and direction depended on baseline eGFR.
Bacterial communities vary across populations and tissue type in red mangroves (Rhizophora mangle, Rhizophoraceae) along an expanding front
Authors: Scherer Brendan P , Mason Olivia U , Mast Austin R
Published: November 2022

Plant-associated microbial communities may be important sources of functional diversity and genetic variation that influence host evolution. Bacteria provide benefits for their hosts, yet in most plant systems we know little about their taxonomic composition or variation across tissues and host range. Red Mangrove (Rhizophora mangle L.) is a vital coastal plant species that is currently expanding poleward and with it, perhaps, its microbiome. We explored variability in bacterial communities across tissues, individuals, and populations. We collected samples from six sample types from 5 to 10 individuals at each of three populations and used 16S rRNA gene (iTag) sequencing to describe their bacterial communities. Core community members and dominant bacterial classes were determined for each sample type. Pairwise PERMANOVA of Bray–Curtis dissimilarity and Indicator Species Analysis revealed significant differences in bacterial communities between sample types and populations. We described the previously unexplored microbiome of the reproductive tissues of R. mangle. Populations and most sample types were associated with distinct communities. Bacterial communities associated with R. mangle are influenced by host geography and sample type. Our study provides a foundation for future work exploring the functional roles of these microbes and their relevance to biogeochemical cycling.
Improved microbial genomes and gene catalog of the chicken gut from metagenomic sequencing of high-fidelity long reads
Authors: Zhang Yan , Jiang Fan , Yang Boyuan , Wang Sen , Wang Hengchao , Wang Anqi , Xu Dong , Fan Wei
Published: November 2022

Background

Due to the importance of chicken production and the remarkable influence of the gut microbiota on host health and growth, tens of thousands of metagenome-assembled genomes (MAGs) have been constructed for the chicken gut microbiome. However, due to the limitations of short-read sequencing and assembly technologies, most of these MAGs are far from complete, are of lower quality, and include contaminant reads.

Results

We generated 332 Gb of high-fidelity (HiFi) long reads from the 5 chicken intestinal compartments and assembled 461 and 337 microbial genomes, of which 53% and 55% are circular, at the species and strain levels, respectively. For the assembled microbial genomes, approximately 95% were regarded as complete according to the “RNA complete” criteria, which requires at least 1 full-length ribosomal RNA (rRNA) operon encoding all 3 types of rRNA (16S, 23S, and 5S) and at least 18 copies of full-length transfer RNA genes. In comparison with the short-read-derived chicken MAGs, 384 (83% of 461) and 89 (26% of 337) strain-level and species-level genomes in this study are novel, with no matches to previously reported sequences. At the gene level, one-third of the 2.5 million genes in the HiFi-derived gene catalog are novel and cannot be matched to the short-read-derived gene catalog. Moreover, the HiFi-derived genomes have much higher continuity and completeness, as well as lower contamination; the HiFi-derived gene catalog has a much higher ratio of complete gene structures. The dominant phylum in our HiFi-assembled genomes was Firmicutes (82.5%), and the foregut was highly enriched in 5 genera: Ligilactobacillus, Limosilactobacillus, Lactobacillus, Weissella, and Enterococcus, all of which belong to the order Lactobacillales. Using GTDB-Tk, all 337 species-level genomes were successfully classified at the order level; however, 2, 35, and 189 genomes could not be classified into any known family, genus, and species, respectively. Among these incompletely classified genomes, 9 and 49 may belong to novel genera and species, respectively, because their 16S rRNA genes have identities lower than 95% and 97% to any known 16S rRNA genes.

Conclusions

HiFi sequencing not only produced metagenome assemblies and gene structures with markedly improved quality but also recovered a substantial portion of novel genomes and genes that were missed in previous short-read-based metagenome studies. The novel genomes and species obtained in this study will facilitate gut microbiome and host–microbiota interaction studies, thereby contributing to the sustainable development of poultry resources.
Utilizing an artificial intelligence system to build the digital structural proteome of reef-building corals
Authors: Zhu Yunchi , Liao Xin , Han Tingyu , Chen J-Y , He Chunpeng , Lu Zuhong
Published: November 2022

Background

Reef-building corals play an important role in the marine ecosystem, and analyzing their proteomes from a structural perspective will exert positive effects on exploring their biology. Here we integrated mass spectrometry with newly published ColabFold to obtain digital structural proteomes of dominant reef-building corals.

Results

Of the 8,382 homologous proteins in Acropora muricata, Montipora foliosa, and Pocillopora verrucosa identified, 8,166 received predicted structures after about 4,060 GPU hours of computation. The resulting dataset covers 83.6% of residues with a confident prediction, while 25.9% have very high confidence.

Conclusions

Our work provides insight-worthy predictions for coral research, confirms the reliability of ColabFold in practice, and is expected to be a reference case in the impending high-throughput era of structural proteomics.