Communications Biology最新文献

Time-restricted feeding (TRF) may modulate metabolic homeostasis through circadian rhythms, but its effects on male fertility remain unclear. This study investigates how different TRF schedules influence testicular homeostasis and spermatogenesis, focusing on the gut-testis axis. Mice are subjected to daytime (DRF) or nighttime (NRF) restricted feeding, compared with ad libitum controls. The results show that NRF reduces testicular index and sperm quality, while DRF shows no adverse effects. Histological analysis confirms decreased numbers of spermatocytes and spermatozoa in the NRF group. 16S rRNA sequencing reveals altered gut microbiota composition in NRF mice, and metabolomics identify elevated levels of kynurenic acid (KYNA), a tryptophan metabolite. KYNA administration inhibits spermatogenesis in a dose-dependent manner, mimicking the NRF phenotype. These findings suggest that feeding timing influences male reproductive health, with gut-derived metabolites like KYNA potentially mediating TRF effects, offering new targets for fertility interventions.

Antibodies are widely used in life sciences and medical therapy. Broadly applicable methods to determine epitope heterogeneity in immunostaining systems are missing. Here, we present a simple-to-use approach to characterize and quantify antibody binding properties that constitute the staining directly in the system of choice. We determine an epitope heterogeneity on the basis of a computational analysis of antibody-dilution immunofluorescence stainings. This allows us to choose signal-specificity maximizing dilutions and to improve signal quantification. Furthermore, the computational analysis provides approaches to obtain a single-channel antibody multiplexing. Our approach could help improving immunostainings in many laboratories by guiding the choice of antibody dilution, by increasing the possibility of antibody-multiplexing in the same color-channel and by allowing for the analysis of binding targets of multi-specific antibodies.

Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the α2₁ helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy.

Cholecystectomy is associated with an increased risk of metabolic syndrome (MetS); however, the underlying mechanism remains unknown. The gallbladder acts as a storage organ for hepatic bile and regulates the feeding/fasting cycles of bile acid (BA) flow in the enterohepatic circulation (EHC). In this study, we aimed to use C57BL/6 mice to investigate the effects of cholecystectomy in the regulation of glucose homeostasis and bile acid metabolism with metabolomics and quantitative RT-PCR. The results show that cholecystectomy increases fasting hepatic BA levels by enhancing EHC. Livers from cholecystectomized (XGB) mice displayed suppression of genes involved in fatty acid oxidation (FAO), abnormal lipid accumulation, and marked remodeling of their metabolomic profiles, particularly a reduction in FAO intermediate acylcarnitines. Many FAO genes were transcriptional targets of the peroxisome proliferator-activated receptor α (PPARα), and BA inhibited PPARα, resulting in impeded FAO. Consistent with this, blocking intestinal BA uptake using an apical sodium-BA transporter inhibitor enhanced fasting hepatic FAO levels and ameliorated metabolic disorders in XGB mice. These findings suggest that cholecystectomy could inhibit fasting hepatic FAO by disturbing the EHC of BA, and reveal the role of the gallbladder in coordinating PPARα-regulated FAO in the liver.

Emotional prosody (EP) processing is vital for social communication. Seed-based functional connectivity has been widely used to probe its neural basis, yet most studies rely on part of predefined regions, introducing uncertainty and bias. Furthermore, although gender and task type modulate its activation pattern, their network-level impact remains unclear. Using activation network mapping (a network-level analogue of meta-analysis), we identified a unified EP network and delineated its modulation by gender and task types (explicit or implicit). Results showed broader activation networks in females compared to males, regardless of the task type. Moreover, explicit tasks recruited additional frontal and sensorimotor regions beyond implicit tasks, supporting hierarchical processing. We also identified associations with specific receptors and diseases like autism and Alzheimer's. These findings underscore the importance of considering gender and task type effects on emotional processing research and provide a network-level neural mechanism underlying emotional prosody.

Mixed-species plantations have been increasingly promoted as a strategy to enhance ecosystem functioning and related ecosystem processes; however, their global impacts on biomass production and nutrient cycling remain uncertain. Here we present a comprehensive meta-analysis based on a random-effects model of 8,450 paired observations from 328 studies spanning diverse climatic zones, stand structures, and silvicultural systems. We demonstrate that species mixing significantly enhances plant biomass and nutrient content compared to monocultures, with positive responses observed across trees, shrubs, litterfall, and both above- and belowground compartments. Mixed-species plantations also increase soil organic carbon, total nitrogen, phosphorus availability, microbial biomass, and leaf nutrient content while maintaining stable soil stoichiometric ratios, collectively reflecting more efficient stand-level nutrient cycling. Importantly, the magnitude of these effects was shaped by climatic and structural contexts, with stronger positive outcomes under warmer and wetter climates, increasing with species richness, and showing unimodal responses to elevation, stand age, and stand density. By synthesizing multi-scale evidence from diverse ecosystems, we reveal that species mixing promotes biomass accumulation, improves nutrient retention, and strengthens biodiversity-nutrient cycling linkages. This study highlights the potential of mixed-species plantations to enhance ecological function, advance forest restoration, and guide plantation management across diverse environmental conditions.

The neuropeptide oxytocin (OT) plays a crucial role in regulating homeostatic responses and complex behaviors, including social interaction. OT can be released from somatodendritic regions, enabling communication through retrograde, autocrine, and volume transmission. However, the mechanisms governing somatodendritic OT dynamics and their impact on neuronal function and behavior are not yet fully understood. Our study identifies SNAP-47, a member of the SNAP-25 protein family highly expressed in the soma of peptidergic neurons in the mouse hypothalamus, where it exhibits a close interaction with OT-containing compartments localized at the plasma membrane. Knocking down SNAP-47 diminishes the recruitment of OT to the plasma membrane in the cell body under both basal conditions and following neuronal stimulation. Reducing endogenous SNAP-47 expression in vivo results in altered spontaneous synaptic transmission in oxytocinergic neurons of the paraventricular nucleus (PVN) and decreases sociability, likely due to disrupted somatic trafficking. These findings provide new insights into the molecular mechanisms governing somatic OT dynamics, its influence on hypothalamic neuromodulation, and its role in OT-dependent behaviors such as social interaction.

The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream transcription factors guiding lineage segregations of Tbr2-expressing RGC into distinct adult ipRGC subtypes. Both factors also control Opn4 expression. Irx1 is expressed in the M3, M4, and M5 subtypes, while Tbx20 is predominantly expressed in M1, M2, M6, and subgroups of M3 and M5. When Irx1 is ablated during retinal development, Opn4 expression is significantly reduced in the M3, M4, and M5 ipRGC groups; however, the formation of Irx1-expressing ipRGCs is not affected. In contrast, when Tbx20 is deleted, a significant number of Tbx20-expressing cells fail to develop while Opn4 expression is down-regulated. These findings reveal two parallel transcription cascades downstream of Tbr2 for controlling ipRGC subtype formation, fate divergence, and maintenance in the adult retina.

Gut microbiota composition has been extensively studied in European and North American pediatric cohorts, as well as in rural African children. Much less attention has been paid to urban African children, whose families have transitioned to a "Western" lifestyle characterized by smaller family sizes, access to perinatal care including C-section delivery, non-traditional food sources and widespread availability of antibiotics. We analyzed fecal samples from ~200 Ethiopian children aged 2-5 years from Adama, Ethiopia, using 16S rRNA gene sequencing and shotgun metagenomics. We found that well-studied factors such as delivery mode, breastfeeding and family size have only minor effects on α-diversity, whereas household crowding (single vs. multiple rooms) and consumption of the traditional fermented cereal Eragrostis tef predict higher α-diversity. Stunted growth and absence of Helicobacter pylori infection were additional factors associated with increased fecal microbial diversity. Metagenomic profiling revealed that rural African signature genera such as Segatella and Prevotella were largely absent; instead, urban Ethiopian children displayed a high Firmicutes/Bacteroidota ratio and enrichment of metabolic pathways linked to a westernized diet, resembling European rather than rural Ethiopian children. These results indicate that an urban westernized lifestyle alters gut microbiota composition, which may be partially offset by a traditional fermented diet.

The entorhinal-hippocampal system constitutes a pivotal neural circuit in the central nervous system. It is critically involved in processing spatial learning and memory. However, the specific neural interactions between entorhinal inputs and intra-hippocampal subcircuits that underlie spatial coding remain elusive. To address this gap, we integrated multimodal approaches including in vivo calcium imaging, dual-color optogenetic manipulation, chemogenetic intervention, electrophysiological recordings, immunohistochemistry, and Morris water maze (MWM) behavior to dissect how entorhinal-hippocampal afferents modulate hippocampal computations. Intriguingly, CA1-projecting CA3 neurons exhibited pronounced hyperactivity during early spatial learning, with activity gradually declining after sustained task performance. Chemogenetic inactivation of medial entorhinal-hippocampal afferents attenuated both neural responses of CA1-projecting CA3 neurons and the performance of spatial learning, hinting that medial entorhinal cortex (MEC) inputs to the hippocampus are essential for animals to execute spatial tasks precisely. By implementing dual-light theta-burst stimulation to co-activate ChrimsonR-expressing CA3-CA1 afferents and Chronos-expressing MEC-CA1 terminals, we observed robust heterosynaptic long-term potentiation in the dorsal CA1 region in vitro brain slice. This neuroplasticity was mediated synergistically by activating both NMDA receptors and voltage-gated calcium channels. Our findings establish that entorhinohippocampal afferents exert multilevel regulatory control over hippocampal function, thereby advancing mechanistic understanding of memory-related neurological pathologies.