The relative contribution of acoustic signals versus movement cues in group coordination and collective decision-making.

To benefit from group living, individuals need to maintain cohesion and coordinate their activities. Effective communication thus becomes critical, facilitating rapid coordination of behaviours and reducing consensus costs when group members have differing needs and information. In many bird and mammal species, collective decisions rely on acoustic signals in some contexts but on movement cues in others. Yet, to date, there is no clear conceptual framework that predicts when decisions should evolve to be based on acoustic signals versus movement cues. Here, we first review how acoustic signals and movement cues are used for coordinating activities. We then outline how information masking, discrimination ability (Weber's Law) and encoding limitations, as well as trade-offs between these, can identify which types of collective behaviours likely rely on acoustic signals or movement cues. Specifically, our framework proposes that behaviours involving the timing of events or expression of specific actions should rely more on acoustic signals, whereas decisions involving complex choices with multiple options (e.g. direction and destination) should generally use movement cues because sounds are more vulnerable to information masking and Weber's Law effects. We then discuss potential future avenues of enquiry, including multimodal communication and collective decision-making by mixed-species animal groups. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamic'.

The gut microbiota regulates acute foreign body reaction and tissue repair after biomaterial implantation.

We hypothesized that the host microbiome may influence foreign body responses following biomaterial implantation. To test this, we implanted a variety of clinically relevant biomaterials into germ-free or antibiotic-treated mice. Surprisingly, these mice displayed less fibrous tissue deposition, reduced host cell recruitment to the implant site, and differential expression of angiogenic and inflammatory markers. These observations were reversed upon fecal microbiome reconstitution, confirming a causal role of the host microbiome. In a clinically relevant disease model, microbiome-depleted mice cleared hyaluronic acid and bone marrow mononuclear cells from ischemic hind limb tissues more slowly, resulting in an improved therapeutic response. Findings were confirmed in pigs which showed reduced fibrotic responses to a variety of implanted materials. Lastly, we profiled changes in the host microbiome following material implantation, implicating several key bacteria phyla.

Long noncoding RNA Smyca coactivates TGF-ß/Smad and Myc pathways to drive tumor progression.

BACKGROUND: Metastasis and chemoresistance are major culprits of cancer mortality, but factors contributing to these processes are incompletely understood. METHODS: Bioinformatics methods were used to identify the relations of Smyca expression to clinicopathological features of human cancers. RNA-sequencing analysis was used to reveal Smyca-regulated transcriptome. RNA pull-down and RNA immunoprecipitation were used to examine the binding of Smyca to Smad3/4 and c-Myc/Max. Chromatin immunoprecipitation and chromatin isolation by RNA purification were used to determine the binding of transcription factors and Smyca to various gene loci, respectively. Real-time RT-PCR and luciferase assay were used to examine gene expression levels and promoter activities, respectively. Xenograft mouse models were performed to evaluate the effects of Smyca on metastasis and chemoresistance. Nanoparticle-assisted gapmer antisense oligonucleotides delivery was used to target Smyca in vivo. RESULTS: We identify lncRNA Smyca for its association with poor prognosis of many cancer types. Smyca potentiates metabolic reprogramming, migration, invasion, cancer stemness, metastasis and chemoresistance. Mechanistically, Smyca enhances TGF-ß/Smad signaling by acting as a scaffold for promoting Smad3/Smad4 association and further serves as a Smad target to amplify/prolong TGF-ß signaling. Additionally, Smyca potentiates c-Myc-mediated transcription by enhancing the recruitment of c-Myc/Max complex to a set of target promoters and c-Myc binding to TRRAP. Through potentiating TGF-ß and c-Myc pathways, Smyca synergizes the Warburg effect elicited by both pathways but evades the anti-proliferative effect of TGF-ß. Targeting Smyca prevents metastasis and overcomes chemoresistance. CONCLUSIONS: This study uncovers a lncRNA that coordinates tumor-relevant pathways to orchestra a pro-tumor program and establishes the clinical values of Smyca in cancer prognosis and therapy.

Long noncoding RNA BCRP3 stimulates VPS34 and autophagy activities to promote protein homeostasis and cell survival.

BACKGROUND: Autophagy plays important roles in cell homeostasis and protein quality control. Long non-coding RNAs (lncRNAs) have been revealed as an emerging class of autophagy regulators, but the majority of them function in regulating the expression of autophagy-related genes. LncRNAs that directly act on the core autophagic proteins remain to be explored. METHODS: Immunofluorescence staining and Western blotting were used to evaluate the function of BCRP3 in autophagy and aggrephagy. RNA immunoprecipitation and in vitro RNA-protein binding assay were used to evaluate the interaction of BCRP3 with its target proteins. Phosphatidylinositol 3-phosphate ELISA assay was used to quantify the enzymatic activity of VPS34 complex. qRT-PCR analysis was used to determine BCRP3 expression under stresses, whereas mass spectrometry and Gene Ontology analyses were employed to evaluate the effect of BCRP3 deficiency on proteome changes. RESULTS: We identified lncRNA BCRP3 as a positive regulator of autophagy. BCRP3 was mainly localized in the cytoplasm and bound VPS34 complex to increase its enzymatic activity. In response to proteotoxicity induced by proteasome inhibition or oxidative stress, BCRP3 was upregulated to promote aggrephagy, thereby facilitating the clearance of ubiquitinated protein aggregates. Proteomics analysis revealed that BCRP3 deficiency under proteotoxicity resulted in a preferential accumulation of proteins acting in growth inhibition, cell death, apoptosis, and Smad signaling. Accordingly, BCRP3 deficiency in proteotoxic cells compromised cell proliferation and survival, which was mediated in part through the upregulation of TGF-ß/Smad2 pathway. CONCLUSIONS: Our study identifies BCRP3 as an RNA activator of the VPS34 complex and a key role of BCRP3-mediated aggrephagy in protein quality control and selective degradation of growth and survival inhibitors to maintain cell fitness.

MetaSquare: an integrated metadatabase of 16S rRNA gene amplicon for microbiome taxonomic classification.

MOTIVATION: Taxonomic classification of 16S ribosomal RNA gene amplicon is an efficient and economic approach in microbiome analysis. 16S rRNA sequence databases like SILVA, RDP, EzBioCloud and HOMD used in downstream bioinformatic pipelines have limitations on either the sequence redundancy or the delay on new sequence recruitment. To improve the 16S rRNA gene-based taxonomic classification, we merged these widely used databases and a collection of novel sequences systemically into an integrated resource. RESULTS: MetaSquare version 1.0 is an integrated 16S rRNA sequence database. It is composed of more than 6 million sequences and improves taxonomic classification resolution on both long-read and short-read methods. AVAILABILITY AND IMPLEMENTATION: Accessible at https://hub.docker.com/r/lsbnb/metasquare_db and https://github.com/lsbnb/MetaSquare. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The formation of "mega-flocks" depends on vegetation structure in montane coniferous forests of Taiwan.

A mixed-species bird flock is a social assemblage where two or more bird species are moving together while foraging and might benefit from increased foraging efficiency and antipredator vigilance. A "mega-flock," which includes flocking species from different vegetation strata, often exhibits high species diversity. Mechanisms for the formation of mega-flocks have not yet been explored. In this study, we evaluated the influence of vegetation structure and bird species diversity in driving the occurrence of mega-flocks. We investigated the composition of mixed-species flocks, local bird communities, and vegetation structure in five vegetation types of two high-elevation sites in central Taiwan. Mega-flocks occurred more frequently in pine woodland than later successional stages of coniferous forests. However, species richness/diversity of local bird communities increased along successional stages. Therefore, vegetation variables exhibit more influence on the occurrence of mega-flocks than local bird communities. Besides foliage height diversity, understory coverage also showed positive effects on flock size of mixed-species flocks. Our results indicated that pine woodlands with more evenly distributed vegetation layers could facilitate the interactions of canopy and understory flocks and increase the formation of mega-flocks and thus the complexity of mixed-species flocks.

miR-103/107 prolong Wnt/ß-catenin signaling and colorectal cancer stemness by targeting Axin2.

Cancer stemness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of stemness fate of cancer cells remain incompletely understood. Here, we show that miR-103/107 stimulate multiple stem-like features in colorectal cancer, including expression of stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these stemness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator of Wnt/ß-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration of Wnt/ß-catenin signaling and a sustained induction of Wnt responsive genes. In colorectal cancer patients, miR-103/107 expression correlates inversely with Axin2 expression and a signature of miR-103/107 high and Axin2 low expression profile correlates with poor prognosis. Together, our study identifies a novel function of miR-103/107 in promoting colorectal cancer stemness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.

Sharpness-induced energy shifts of quantum well states in Pb islands on Cu(111).

We elucidate that the tip sharpness in scanning tunneling microscopy (STM) can be characterized through the number of field-emission (FE) resonances. A higher number of FE resonances indicates higher sharpness. We observe empty quantum well (QW) states in Pb islands on Cu(111) under different tip sharpness levels. We found that QW states observed by sharper tips always had lower energies, revealing negative energy shifts. This sharpness-induced energy shift originates from an inhomogeneous electric field in the STM gap. An increase in sharpness increases the electric field inhomogeneity, that is, enhances the electric field near the tip apex, but weakens the electric field near the sample. As a result, higher sharpness can increase the electronic phase in vacuum, causing the lowering of QW state energies. Moreover, the behaviors of negative energy shift as a function of state energy are entirely different for Pb islands with a thickness of two and nine atomic layers. This thickness-dependent behavior results from the electrostatic force in the STM gap decreasing with increasing tip sharpness. The variation of the phase contributed from the expansion deformation induced by the electrostatic force in a nine-layer Pb island is significantly greater, sufficient to effectively negate the increase of electronic phase in vacuum.

Dihydromyricetin from Ampelopsis grossedentata inhibits melanogenesis through down-regulation of MAPK, PKA and PKC signaling pathways.

The inhibitory effects of dihydromyricetin purified from Ampelopsis grossedentata on melanogenesis and its antioxidant characteristics were investigated. Assays of tyrosinase activities and melanin content in B16F10 mouse melanoma cells were carried out spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in dihydromyricetin-mediated depigmentation were also examined using specific protein kinase regulators. The results revealed that dihydromyricetin effectively suppresses intracellular tyrosinase activity and decreases melanin amount in cells. Dihydromyricetin also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) and reactive species (RS) levels. Our results indicated that dihydromyricetin inhibits melanogenesis through its antioxidant properties and by downregulating protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinases (MAPK) signaling pathways. The present study indicates that dihydromyricetin has the potential to be developed into a depigmentation skin care product.

Presynaptic 5-HT1B receptor-mediated synaptic suppression to the subplate neurons in the somatosensory cortex of neonatal rats.

Serotonin (5-HT), the target of numerous psychiatric medicines, plays important roles in neural development. In this study we examined the direct effects of 5-HT on the physiological properties of neurons in the cortical subplate, a structure that develops early in life and is important for the maturation of cortical circuits. Acute brain slices were prepared from neonatal rats and the intrinsic and synaptic properties of subplate neurons (SPns) were evaluated before and after 5-HT bath-application. In all concentrations tested, 5-HT did not affect the intrinsic properties of SPns. However, thalamus-evoked excitatory postsynaptic currents (eEPSCs) in SPn were significantly suppressed by 5-HT in a dose-dependent manner. Because 5-HT did not affect AMPA- or NMDA-induced currents, it is unlikely that a 5-HT-mediated postsynaptic mechanism reduced EPSCs. Subsequent to 5-HT application, increased paired-pulse ratios and decreased MK-801 blocking rates were noted, indicating the presence of a presynaptic 5-HT receptor-mediated suppressive effect in the thalamocortical afferent (TCA)-SPn synapses. To elucidate the type(s) of 5-HT receptor involved in this process, various 5-HT receptor agonists and antagonists were tested. CP93129, a 5-HT(1B) receptor agonist, mimicked the effect of 5-HT and in the contrary, the 5-HT(1B) receptor antagonist SB224289 prevented 5-HT-mediated synaptic suppression. Our cumulative data demonstrated the presynaptic 5-HT(1B) receptor-mediated suppressive effect on the excitatory synapses between TCAs and SPns in the somatosensory cortex of neonatal rats. Early exposure to drugs that might interrupt 5-HT homeostasis should be considered.

Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain.

Disruption of disrupted-in-schizophrenia 1 (DISC1), a candidate susceptibility gene for schizophrenia, was first identified in a large Scottish family in which many members suffered from various psychiatric disorders, including schizophrenia. To model the Scottish DISC1 truncation, we established a Disc1 mutant mouse line in which the 129S6/SvEv 25-bp deletion variant was transferred into the C57BL/6J strain by backcrossing. A battery of behavioral tasks was conducted to evaluate the basic behaviors and cognitive function of these mice. In heterozygote and homozygote Disc1 mutant (Het and Homo) mice, behavioral impairments were noted in working memory test which is thought to be mediated by the function of the medial prefrontal cortex (mPFC). The properties of mPFC neurons were characterized in both morphological and physiological aspects. The dendritic diameters were decreased in layer II/III mPFC pyramidal neurons of Het and Homo mice, whereas a significant reduction in spine density was observed in Homo mice. Neuronal excitability was declined in layer II/III mPFC pyramidal neurons of Het and Homo mice, yet increased transmitter release was identified in Homo mice. Thus, the structural and functional alterations of the mPFC in Het and Homo mice might account for their cognitive impairment. Since most of the gene knockout mice are generated from 129 substrain-derived embryonic stem cells, potential Disc1 deficiency should be considered.

Widely tunable difference frequency generation source for high-precision mid-infrared spectroscopy.

We have developed a widely tunable mid-infrared difference frequency generation (DFG) source by mixing ~ 1 W Ti:sapphire laser and 6 W Nd:YAG laser beams in a 50-mm MgO-doped long periodically poled lithium niobate (MgO:PPLN). The power of the DFG source is > 2 mW over the tuning range of 2.66-4.77 µm and its free-running linewidth is about 100 kHz. Combining various frequency stabilisation schemes for the Nd:YAG laser and the Ti:sapphire laser, the DFG frequency can be precisely controlled. Besides, its frequency can be determined better than 12 kHz by measuring the Ti:sapphire laser frequency using an optical frequency comb. Two high resolution spectroscopic studies on (12)C(16)O(2) molecule are demonstrated using this DFG source. The saturation spectra of R(18) and R(60) transitions of 00(0)1 ← 00(0)0 fundamental band at 4.2 µm and P(20) transition of [10(0)1, 02(0)1](I) ← 00(0)0 band at 2.7 µm have been observed and their absolute transition frequencies are measured with an accuracy better than 30 kHz.

Evidence for structural and functional changes of subplate neurons in developing rat barrel cortex.

In the developing sensory cortex, the subplate could serve as a transient relay station between the thalamus and cortical plate and assists the formation of thalamocortical projection. While the thalamus-layer IV connection is formed, the thalamic activation of subplate is diminished. In the present study, we aimed to explore the mechanism which may attribute to the decline of subplate activity. To resolve this issue, the developmental changes of subplate neurons (SPns) in rat somatosensory cortex were examined during the first two postnatal weeks which covers the stages prior and subsequent to the establishment of thalamocortical connection. During development, more SPns exhibited regular-spiking firing pattern and the membrane properties of SPns displayed a continual trend of maturation. In the meantime, the excitability of SPns decreased as revealed by increasing rheobase and rightwardly shifted frequency-current curves. On the other hand, increasing paired-pulse ratio and slowing MK-801 blocking rate were noted during development, implying the reduction of presynaptic transmitter release. Morphologically, the size of SPn soma increased with age while the shape became flat. The total length, branching nodes and segments of dendrites increased significantly during the first week. However, after peaking around day 10, these values decreased, implying a pruning process. Our findings here propose that the reduction of neuronal excitability, synaptic transmission and dendritic complexity may attribute to the decline of functional connectivity between thalamus and subplate and reduction of subplate activity while the thalamocortical pathway is established.

Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation.

The mesocorticolimbic system contains dopamine (DA)-producing neurons in the ventral tegmental area (VTA) and their projection targets, including the medial prefrontal cortex (mPFC), amygdala (AMY) and nucleus accumbens (NAc). Disruption of this system might attribute to mental illnesses. In the present study, we adopted the postweaning social isolation paradigm to model neuropsychiatric disorders and studied the functional and structural changes of the mesocorticolimbic system. After 8-9 weeks of isolation, rats exhibited hyperlocomotor activity and impaired sensorimotor gating compared to group-reared controls. However, the number of tyrosine hydroxylase-positive VTA neurons and the volume of VTA were not affected. Comparing with group-reared controls, the DA levels in the isolation-reared were not altered in the VTA, mPFC and NAc but decreased in the AMY. In the structural aspect, dendritic features of layer II/III pyramidal mPFC neurons; pyramidal neurons in the basolateral nucleus of amygdala (BLA) and medium spiny neurons in the core region of the NAc (NAcc) were examined. Interestingly, the neuronal changes were region-specific. The mPFC neurons had reduced dendritic complexity, spine density and elongated terminal branches. The BLA neurons had extensive dendritic arbors with short branches but unchanged spine density. The NAcc neurons had reduced total dendritic length but the segment length and spine density remained the same. Together, the results demonstrated the structural and functional changes in the mesocorticolimbic DA system of socially isolated rats. These changes may account for the behavioral impairments in these rats and attribute to the susceptibility to mental disorders related to schizophrenia and depression.

Neonatal fluoxetine exposure affects the action potential properties and dendritic development in cortical subplate neurons of rats.

Selective serotonin reuptake inhibitor (SSRI)-type antidepressants might be given to depressive pregnant women and the developing fetuses are thus exposed to these drugs. Since serotonin plays important roles in the maturation of the nervous system, early SSRI exposure might influence the fetal brain development. To test this hypothesis, we treated the neonatal rat pups with fluoxetine (Flx) from the day of birth to postnatal day (P) 4, comparable to the third trimester of human gestation, and observed the physiological and morphological features of subplate neurons (SPns), a group of cells important for early cortical development and vulnerable to neonatal neural insults. Using whole-cell patch-clamp recording technique, we examined the passive membrane properties and characteristics of action potential (AP). In SPns of Flx-treated rats, the rheobase for generating an AP was increased and the width of APs was reduced, especially in the falling phase. In the morphological aspect, the dendritic remodeling of SPns including dendritic branching, elongation and pruning were affected by early Flx treatment. Together, our results demonstrate that the teratogenic effect of early SSRI exposure on the structure and function of developing SPns and these changes may lead to undesired brain activity and distorted behaviors later in life.

mGluR5 in cortical excitatory neurons exerts both cell-autonomous and -nonautonomous influences on cortical somatosensory circuit formation.

Glutamatergic neurotransmission plays important roles in sensory map formation. The absence of the group I metabotropic glutamate receptor 5 (mGluR5) leads to abnormal sensory map formation throughout the mouse somatosensory pathway. To examine the role of cortical mGluR5 expression on barrel map formation, we generated cortex-specific mGluR5 knock-out (KO) mice. Eliminating mGluR5 function solely in cortical excitatory neurons affects, not only the whisker-related organization of cortical neurons (barrels), but also the patterning of their presynaptic partners, the thalamocortical axons (TCAs). In contrast, subcortical whisker maps develop normally in cortical-mGluR5 KO mice. In the S1 cortex of cortical-mGluR5 KO, layer IV neurons are homogenously distributed and have no clear relationship to the location of TCA clusters. The altered dendritic morphology of cortical layer IV spiny stellate neurons in cortical-mGluR5 KO mice argues for a cell-autonomous role of mGluR5 in dendritic patterning. Furthermore, morphometric analysis of single TCAs in both cortical- and global-mGluR5 KO mice demonstrated that in these mice, the complexity of axonal arbors is reduced, while the area covered by TCA arbors is enlarged. Using voltage-clamp whole-cell recordings in acute thalamocortical brain slices, we found that KO of mGluR5 from cortical excitatory neurons reduced inhibitory but not excitatory inputs onto layer IV neurons. This suggests that mGluR5 signaling in cortical excitatory neurons nonautonomously modulates the functional development of GABAergic circuits. Together, our data provide strong evidence that mGluR5 signaling in cortical principal neurons exerts both cell-autonomous and -nonautonomous influences to modulate the formation of cortical sensory circuits.