A modulation wave approach is used to interpret the coupled longer range as well as truly short range order hidden in the highly structured diffuse intensity distributions of three representative such systems. The longer range as well as the truly short range order simultaneously encoded in such highly structured diffuse intensity distributions is highlighted.

Current data collection strategies in electron cryo-microscopy (cryo-EM) record multiframe movies with static optical settings. This limits the number of adjustable parameters that can be used to optimize the experiment. Here, a method for fast and accurate defocus (FADE) modulation during movie acquisition is proposed. It uses the objective lens aperture as an electrostatic pole that locally modifies the electron beam potential. The beam potential variation is converted to defocus change by the typically undesired chromatic aberration of the objective lens. The simplicity, electrostatic principle and low electrical impedance of the device allow fast switching speeds that will enable per-frame defocus modulation of cryo-EM movies. Researchers will be able to define custom defocus `recipes' and tailor the experiment for optimal information extraction from the sample. The FADE method could help to convert the microscope into a more dynamic and flexible optical platform that delivers better performance in cryo-EM single-particle analysis and electron cryo-tomography.

Karolina Losenkova, Mariachiara Zuccarini, Marika Karikoski, Juha Laurila, Detlev Boison, Sirpa Jalkanen, and Gennady G. Yegutkin

Extracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects and becomes an important therapeutic target for cancer, which has been translated into clinical trials. This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprised of (a) the ectoenzymatic breakdown of ATP via sequential nucleotide pyrophosphatase/phosphodiesterase-1, ecto-5’-nucleotidase/CD73 and adenosine deaminase reactions, and ATP re-synthesis through counteracting adenylate kinase and nucleoside diphosphokinase; (b) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (c) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O₂ for 24 hours triggered ~2-fold up-regulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer.

A new paper in CRANIO Journal explains how the Sphenopalatine Ganglion is a common thread linking these disorders. Self-Administration of SPG Blocks and Neuromodulation on the Ganglion can dramtically improve patients quality of life.

Provided herein are methods, compounds, and compositions for reducing expression of PTP1B mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

In some embodiments, nerves surrounding arteries or leading to organs are targeted with energy sources to correct or modulate physiologic processes. In some embodiments, different types of energy sources are utilized singly or combined with one another. In some embodiments, bioactive agents or devices activated by the energy sources are delivered to the region of interest and the energy is enhanced by such agents.

Methods and systems for decoding a signal include compensating for impairments in a received signal using at least carrier phase estimation, where residual phase error remains after compensation; calculating symbol log-likelihood ratios (LLRs) for symbols in the compensated signal using Monte Carlo integration; demapping the symbols in the compensated signal using the symbol LLRs and extrinsic information from signal decoding to produce one or more estimated codewords; and decoding each estimated codeword with a decoder that generates a decoded codeword and extrinsic information.

Various embodiments provide for systems and methods for signal conversion of one modulated signal to another modulated signal using demodulation and then re-modulation. According to some embodiments, a signal receiving system may comprise an I/Q demodulator that demodulates a first modulated signal to an in-phase (“I”) signal and a quadrature (“Q”) signal, an I/Q signal adjustor that adaptively adjusts the Q signal to increase the signal-to-noise ratio (SNR) of a transitory signal that is based on a second modulated signal, and an I/Q modulator that modulates the I signal and the adjusted Q signal to the second modulated signal. To increase the SNR, the Q signal may be adjusted based on a calculated error determined for the transitory signal during demodulation by a demodulator downstream from the I/Q modulator.

A controller for a DC motor comprises an output switching element configured to couple to the DC motor; an input switching element coupled to the output switching element; a pulse width modulated (PWM) signal coupled to a control terminal of the input switching element and a supply voltage applied to the output switching element. A resistive-capacitive (RC) network may be coupled to a control terminal of the output switching element, with the RC network being configured to integrate the PWM signal into a DC voltage. A first resistive network may be configured to set a bias for the output switching element when the input switching element is turned off, and a second resistive network may be configured to set the bias for the output switching element when the input switching element is turned on, such that the controller is effective to provide zero-to-full supply voltage control to the DC motor.

Embodiments of the present method and system permit an effective method for determining the optimum selection of pulse width modulation polarity and type including determining machine parameters, inputting the machine parameters into a predicted duty cycle module, determining the optimum polarity of the pulse width modulation for a predicted duty cycle based on a pulse width modulation generation algorithm, and determining the optimum type of the pulse width modulation for a predicted duty cycle based on the pulse width modulation generation algorithm.

A control system (128) for controlling a switched reluctance (SR) machine (110) having a rotor (116) and a stator (118) is provided. The control system (128) may include a converter circuit (122) operatively coupled to the stator (118) and including a plurality of switches (132) in selective communication with each phase of the stator (118) and a controller (130) in communication with each of the stator (118) and the converter circuit (122). The controller (130) may be configured to determine a position of the rotor (116) relative to the stator (118), and generate a modulated switching frequency (152) based on the rotor position.

Various embodiments associated with an at least fourth-order cumulant of a signal are described. The at least fourth-order noise-insensitive cumulant of the signal can be taken and compared against an at least fourth-order noise-insensitive cumulant of known signals. A match can be found between the signal and a known signal and from this match, a demodulation scheme of the signal can be determined. The demodulation scheme can be used to demodulate the signal.

Groups of phase shifted Pulse Width Modulation signals are generated that maintain their duty-cycle and phase relationships as a function of the period of the PWM signal frequency. The multiphase PWM signals are generated in a ratio-metric fashion so as to greatly simplify and reduce the computational workload for a processor used in a PWM system. The groups of phase shifted PWM signals may also be synchronized with and automatically scaled to match external synchronization signals.

An amplifier receives an amplitude signal of a polar modulated signal at a base terminal of a transistor and receives a phase modulated carrier signal of the polar modulated signal at the base terminal of the transistor. The amplifier combines the amplitude signal and the phase modulated signal to produce a full complex waveform at a collector terminal of the transistor.

A new coded continuous phase modulation (CPM) scheme is proposed to enhance physical layer performance of the current DVB-RCS standard for a satellite communication system. The proposed CPM scheme uses a phase pulse design and combination of modulation parameters to shape the power spectrum of CPM signal in order to improve resilience to adjacent channel interference (ACI). Additionally, it uses a low complexity binary convolutional codes and S-random bit interleaving. Phase response using the proposed CPM scheme is a weighted average of the conventional rectangular and raised-cosine responses and provides optimum response to minimize frame error rate for a given data rate.

A PWM circuit that can have two refresh rates, including: a first PWM signal generator and a second PWM signal generator; wherein the first PWM signal generator and the second PWM signal generator respectively control refresh rates in two dimensions of an output data generated from a target apparatus. A PWM signal generation method that can have two refresh rates, including: generating a first PWM signal; generating a second PWM signal; and controlling refresh rates in different dimensions of an output data generated from a target apparatus respectively by using the first PWM signal and the second PWM signal.

A digital pulse width modulation controller includes a pulse width modulation controller, a selection unit having at least one selector, a comparison unit having at least one comparator, and a signal conversion unit having at least one digital-to-analog converter. The digital-to-analog converter generates a reference current and/or voltage. The comparator receives the reference current and/or voltage, and performs a comparison operation to generate a comparison signal based on a feedback signal. The selector selects one selection signal to input into the pulse width modulation controller, which receives other parameters set by a user or the system at the same time so as to control characteristics of the digital pulse width modulation signals, thereby improving the electric properties of a loading circuit.

Techniques and mechanisms for configuring logic to implement a signal modulation. In an embodiment, the logic includes a finite impulse response (FIR) module comprising circuitry. The selection circuitry may be operable to concurrently receive signals from latch circuitry of the FIR module and, based on the signals, to select an input group of the selection circuitry and to output a voltage identifier. In another embodiment, configuration logic is operable to set an operational mode which determines a total number of concurrent input signals, received by the FIR module, which the FIR module will use to select an input group for generating an output representing a voltage level.

A rail-to-rail comparator including a first comparison unit connected to a first terminal and configured to compare differential input signals to differential reference voltages; a second comparison unit connected to a second terminal and configured to compare the differential input signals to the differential reference voltages; and an output unit configured to be driven in response to a clock signal and to generate a complementary output signal according to comparison results of the first and second comparison units.

A time-varying formant is generated at a formant frequency by generating first and second harmonic phase signals having first and second harmonic numbers, respectively, in relation to a modulation frequency. The first and second harmonic phase signals are generated in proportion to a master phase signal, which varies at the modulation frequency, modulo a factor corresponding to their harmonic numbers. First and second sound signals, based on the first and second harmonic phase signals, are frequency modulated to create an arbitrarily rich harmonic spectrum, depending on an FM index. The time-varying formant is generated by generating a time-varying combination of the first and second harmonic sound signals, weighting the first and second harmonic sound signals in accordance with their spectral proximities to the formant frequency. One or more of the harmonic numbers are updated when the time-varying formant frequency passes the frequency of either sound signal.

A device for mixing multiple (N) pulse density modulated (PDM) bit streams of a bit rate, the device comprises an input logic, an error accumulation circuit, an error correction circuit and an adder of more than N bits; wherein the device is arranged to output an output PDM bit stream that represents a mixture of the multiple input PDM bit streams; wherein the output PDM bit stream comprises a plurality of output PDM bits, wherein a certain output PDM bit of a plurality of output PDM bits that form the output PDM bit stream is generated during a certain clock cycle; wherein the input logic is arranged to select, during each fraction of the certain clock cycle, a current bit of a selected PDM bit stream, wherein different PDM bit streams are selected during different fragments of the certain clock cycle; wherein the error accumulation circuit is arranged to store intermediate values during a first fraction till a penultimate fraction of the certain clock signal and to store a last value during a last fraction of the certain clock signal.

A frequency modulator includes a digitally-controlled oscillator (DCO) arranged for producing a frequency deviation in response to a modulation tuning word and a phase-locked loop (PLL) tuning word. In addition, another frequency modulator includes a DCO and a DCO interface circuit. The DCO is arranged for producing a frequency deviation in response to an integer tuning word and a fractional tuning word. The DCO interface circuit is arranged for generating the integer tuning word and the fractional tuning word to the DCO, wherein the fractional tuning word is obtained through asynchronous sampling of a fixed-point tuning word.

Embodiments of digital high-speed bi-phase modulator and method for bi-phase modulation are generally described herein. In some embodiments, the digital high-speed bi-phase modulator comprises a high-speed digital divider, a high-speed digital multiplexer, and matched signal paths provided between the divider and the multiplexer. The high-speed digital divider is configured to receive a carrier signal and generate complementary output signals. The high-speed digital multiplexer is configured to switch between the complementary output signals and generate a bi-phase modulated output at a carrier frequency (fc) modulated with a bi-phase code. The bi-phase code may be provided to control inputs of the multiplexer.

A modulation apparatus for a class D switching amplifier is capable of reducing power consumption of an Electro-Migration Interface (EMI) of an output end and a gate driver end in a zero input signal. The modulation apparatus for a class D switching amplifier includes a control unit for detecting and outputting a control signal which is a common signal component of a first modulation signal modulated by using a first input signal and a second modulation signal modulated by using a second input signal; and is characterized by feedback of a first output signal, a second output signal and a common output signal outputted by using the first modulation signal, the second modulation signal and the control signal through an input of the modulation apparatus.

A communications system includes a target receiver having a passband and configured to receive an intended signal within the passband. The communications system also includes a jammer configured to jam the target receiver from receiving the intended signal. The jammer has at least one antenna, a jammer receiver coupled to the at least one antenna, a jammer transmitter coupled to the at least one antenna, and a controller configured to cooperate with the jammer receiver. The controller is configured to detect the intended signal and to generate an interfering signal comprising a continuous phase modulation (CPM) waveform having a constant envelope so that the interfering signal at least partially overlaps the passband of the target receiver.

In various embodiments, systems and methods for generating high-precision pulse-width modulation include a delay-locked loop comprising multiple delay units having time-variable delays, control logic for selecting a subset S of the multiple delay units to thereby generate a time-invariant shift amount having a precision finer than that of a system clock and circuitry for applying the shift amount to rising and falling edges of a pulse-width modulation waveform to thereby generate a high-precision pulse-width modulation waveform.

A modulation method is provided. The modulation method includes the steps of receiving multiple sinusoidal signals, obtaining the maximum value of the sinusoidal signals, obtaining the median value of the sinusoidal signals, and obtaining the minimum value of the sinusoidal signals within a period to generate a difference between the maximum value and the minimum value, generating a difference according to an upper limit and a lower limit of a predetermined comparison value, and comparing the two differences to generate an optimized modulation signal.

The present invention relates to a digital modulation method and a corresponding modulator. The modulator comprises a transcoder (110) followed by a FIFO register (120) and a 2-PSK modulator (130). The transcoder codes a binary word of fixed size into a code word of variable size using a transcoding table. The transcoding table codes at least one first binary word, leading to a first number of phase transitions at the output of the modulator, into a second word of size greater than that of the first word, leading to, at the output of the modulator, a second number of phase transitions less than the first number of phase transitions.

A memristor-based emulator including a memristor circuit for use in digital modulation that includes a first current feedback operational amplifier (CFOA) having multiple terminals in communication with a capacitor Cd and in further communication with a resistor Ri. A second CFOA having multiple terminals is in communication with the first CFOA and is adapted to be in further communication with a voltage vM to provide an input current iM for integration by a capacitor Ci. A nonlinear resistor is in communication with the second CFOA. A third CFOA having multiple terminals is in communication with the nonlinear resistor and is in further communication with the first CFOA and a resistor Rd. The third CFOA and the resistor Rd act as an inverting amplifier associated with the nonlinear resistor to increase a current gain to increase a difference between ON and OFF values of a resistance of a realized memristor.

A method for phase modulation of a carrier signal from a transmitter to a contactless transponder in which data is coded as consecutive symbols, each corresponding to a predefined number of carrier cycles, and in which a symbol time is at least two cycles of the carrier signal includes, at the transmitter, spreading a phase jump of a symbol in relation to a preceding symbol over a first part of the symbol time. The establishment of the phase jump is completed in the first part of the symbol time. The periods of the cycles are constant during a second part of the symbol time.

A wireless communication node (10) dynamically estimates passive intermodulation (PIM) interference coupled into the node's receive path from the transmission of a composite signal through the node's transmit path. The node (10) then cancels the estimated PIM interference in the receive path. In some embodiments, the node dynamically estimates the PIM interference as a function of the composite signal that models PIM interference generation and coupling in the node (10) according to one or more coefficients (30). The coefficients (30) may be determined by transmitting a test signal (34) during a test stage, when the node (10) is not scheduled to receive any signal. Later, when the composite signal (18) is transmitted, the node (10) uses the coefficients (10) to dynamically estimate and cancel the resulting PIM interference.

Systems and methods are provided for generating an amplitude modulation signal to a switchmode power amplifier. A DC to DC switch is configured to receive a DC input voltage and to provide a DC output voltage. A low dropout regulator is configured to provide the amplitude modulation signal according to a modulation control signal received by the low dropout regulator. A control circuit is configured to establish a nominal operating power level for the power amplifier via the amplitude modulation signal and to maintain a minimum voltage difference between the DC output voltage and the low dropout regulator output. A modulator control circuit is configured to provide the modulation control signal to the low dropout regulator. The modulator control circuit provides the transition from a high amplitude to a low amplitude and a transition from the low amplitude to the high amplitude at configurable first and second slopes, respectively.

The present invention is directed to data communication system and methods. More specifically, embodiments of the present invention provide an apparatus that receives data from multiple lanes, which are then synchronized for transcoding and encoding. A pseudo random bit sequence checker may be coupled to each of the plurality of lanes, which is configured to a first clock signal A. Additionally, an apparatus may include a plurality of skew compensator modules. Each of the skew compensator modules may be coupled to at least one of the plurality of lanes. The skew-compensator modules are configured to synchronize data from the plurality of lanes. The apparatus additionally includes a plurality of de-skew FIFO modules. Each of the de-skew compensator modules may be coupled to at least one of the plurality of skew compensator modules.

A Bluetooth Low Energy (BLE) device, having a demodulator configured to translate in-phase and quadrature components of a received BLE signal into a differential phase signal; an estimator configured to estimate a frequency offset of the differential phase signal; and a detector configured to detect information in the differential phase signal corrected by the estimated frequency offset.

A radio-frequency (RF) switch includes a field-effect transistor (FET) disposed between a first node and a second node, the FET having a source, a drain, a gate, and a body. The RF switch further includes a coupling circuit including a first path and a second path, the first path being connected between the gate and one of the source or the drain via a first resistor in series with a first capacitor, the second path being connected between the body and the one of the source or the drain via a second resistor in series with a second capacitor, the coupling circuit configured to allow discharge of interface charge from either or both of the gate and body.

A fluid analyzer includes an optical source and an optical detector defining an optical beam path through an interrogation region of a fluid flow cell. Flow-control devices conduct analyte and reference fluids through a channel and the interrogation region, and manipulate fluid flow in response to control signals to move a fluid boundary separating the analyte and reference fluids across the interrogation region. A controller generates control signals to (1) cause the fluid boundary to be moved across the interrogation region accordingly, (2) sample an output signal from the optical detector at a first interval during which the interrogation region contains more analyte fluid than reference fluid and at a second interval during which the interrogation region contains more reference fluid than analyte fluid, and (3) determine from samples of the output signal a measurement value indicative of an optically measured characteristic of the analyte fluid.

K-Devices has announced the release of an iOS/AUv3 version of WOV, an effect plugin for creating a wide range of textural transmutation, from familiar static tremolo waves to evolving glitchy stutters. WOV for IOS comes with a set of intriguing presets from sound designers Richard Devine and Stév! It is a deeply creative tool that […]

The post K-Devices releases WOV creative modulation effect plugin for iOS appeared first on rekkerd.org.

Chronic back pain from a military training accident in 1980 was slowly ruining Dennis Shiller's life until he discovered neuromodulation.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

Galatia Cleanthous and Athanasios G. Georgiadis
Trans. Amer. Math. Soc. 373 (2020), 3323-3356.
Abstract, references and article information

Elena Lorente
Apr 7, 2020; 0:RA120.002014v1-mcp.RA120.002014
Research

The human leucocyte antigen (HLA)-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with ankylosing spondylitis (AS), a chronic inflammatory spondyloarthropathy. This study examined the effect of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones and the peptides were identified using high throughput mass spectrometry analyses. The relative abundance of thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of antigen binding site of HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues, and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and P positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from Campylobacter jejuni. These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.

Jens Juul Holst
Dec 1, 2004; 53:S197-S204
Section V: The Incretin Pathway

Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4⁺Foxp3⁺ regulatory T cells (T_regs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded T_regs in T1D and solid-organ transplant recipients are limited by poor T_reg engraftment without host manipulation. We showed that T_reg engraftment and therapeutic benefit in nonautoimmune models required ablative host conditioning. Here, we evaluated T_reg engraftment and therapeutic efficacy in the nonobese diabetic (NOD) mouse model of autoimmune diabetes using nonablative, combinatorial regimens involving the anti-CD3 (αCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6–1) antibody complex. We demonstrate that αCD3 alone induced substantial T-cell depletion, impacting both conventional T cells (T_conv) and T_regs, subsequently followed by more rapid rebound of T_regs. Despite robust depletion of host T_conv and host T_regs, donor T_regs failed to engraft even with interleukin-2 (IL-2) support. A single dose of CyP after αCD3 depleted rebounding host T_regs and resulted in a 43-fold increase in donor T_reg engraftment, yet polyclonal donor T_regs failed to reverse diabetes. However, infusion of autoantigen-specific T_regs after αCD3 alone resulted in robust T_reg engraftment within the islets and induced remission in all mice. This novel combinatorial therapy promotes engraftment of autoantigen-specific donor T_regs and controls islet autoimmunity without long-term immunosuppression.

Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning.

SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.

ABSTRACT

Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Here, we show that myositis induced by Ross River virus (RRV) infection is driven by CD11b^hi Ly6C^hi inflammatory monocytes and followed by the establishment of a CD11b^hi Ly6C^lo CX₃CR1⁺ macrophage population in the muscle upon recovery. Selective modulation of CD11b^hi Ly6C^hi monocyte migration to infected muscle using immune-modifying microparticles (IMP) reduced disease score, tissue damage, and inflammation and promoted the accumulation of CX₃CR1⁺ macrophages, enhancing recovery and resolution. Here, we detail the role of immune pathology, describing a poorly characterized muscle macrophage subset as part of the dynamics of alphavirus-induced myositis and tissue recovery and identify IMP as an effective immunomodulatory approach. Given the lack of specific treatments available for alphavirus-induced pathologies, this study highlights a therapeutic potential for simple immune modulation by IMP in infected individuals in the event of large alphavirus outbreaks.

IMPORTANCE Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX₃CR1⁺ macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX₃CR1⁺ macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.

ABSTRACT

Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum. Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.

Key Points

Daniel J. Tobiansky, Meredith C. Miles, Franz Goller, and Matthew J. Fuxjager

Performance trade-offs can dramatically alter an organism's evolutionary trajectory by making certain phenotypic outcomes unattainable. Understanding how these trade-offs arise from an animal's design is therefore an important goal of biology. To explore this topic, we study how androgenic hormones, which regulate skeletal muscle function, influence performance trade-offs relevant to different components of complex reproductive behaviour. We conduct this work in golden-collared manakins (Manacus vitellinus), a Neotropical bird in which males court females by rapidly snapping their wings together above their back. Androgens help mediate the snap displays by radically increasing the twitch speed of a dorsal wing muscle [scapulohumeralis caudalis (SH)], which actuates the bird's wing-snap. Through hormone manipulations and in situ muscle recordings, we test how these positive effects on SH speed influence trade-offs with endurance. Indeed, this trait impacts the display by shaping signal length. We find that androgen-dependent increases in SH speed incur a cost to endurance, particularly when this muscle performs at its functional limits. Moreover, when behavioural data are overlaid on our muscle recordings, displaying animals appear to balance display speed with fatigue-induced muscle fusion (physiological tetanus) to generate the fastest possible signal while maintaining an appropriate signal duration. Our results point to androgenic hormone action as a functional trigger of trade-offs in sexual performance—they enhance one element of a courtship display, but in doing so, impede another.