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The piRNA pathway protects germline genomes from selfish genetic elements (e.g. transposons) through their transcript cleavage in the cytoplasm and/or their transcriptional silencing in the nucleus. Here, we describe a mechanism by which the nuclear and cytoplasmic arms of the piRNA pathway are linked. We find that during mitosis of Drosophila spermatogonia, nuclear Piwi interacts with nuage, the compartment that mediates the cytoplasmic arm of the piRNA pathway. At the end of mitosis, Piwi leaves nuage to return to the nucleus. Dissociation of Piwi from nuage occurs at the depolymerizing microtubules of the central spindle, mediated by a microtubule-depolymerizing kinesin, Klp10A. Depletion of klp10A delays the return of Piwi to the nucleus and affects piRNA production, suggesting the role of nuclear-cytoplasmic communication in piRNA biogenesis. We propose that cell cycle-dependent communication between the nuclear and cytoplasmic arms of the piRNA pathway may play a previously unappreciated role in piRNA regulation., Author summary The piRNA pathway that defends germline from selfish elements operates in two subpathways, one mediated by Piwi in Drosophila to silence transcription of targets in the nucleus and the other mediated by Aub and Ago3 to cleave transcripts of targets in the cytoplasm. How these two subpathways might coordinate with each other, particularly at the cell biological level, remains elusive. This study shows that Piwi interacts with Aub/Ago3 specifically in mitosis in nuage, the organelle that serves as the platform for piRNA cytoplasmic subpathway. Piwi returns to the nucleus at the end of mitosis, and our study suggests that dissociation of Piwi from nuage is facilitated by microtubule depolymerization by a kinesin Klp10A at the central spindle. We propose that cell-cycle-dependent interaction of two piRNA subpathways may play an important role in piRNA production.

Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here, we show that Alms1a, aDrosophilahomolog of the human ciliopathy gene Alstrom syndrome, is enriched on the mother centrosome inDrosophilamale germline stem cells (GSCs). Depletion ofalms1ain GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication, suggesting that Alms1a has a stem-cell-specific function in centrosome duplication. Alms1a interacts with Sak/Plk4, a critical regulator of centriole duplication, more strongly at the GSC mother centrosome, further supporting Alms1a’s unique role in GSCs. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.

Cytoplasmic cilia, which are found in human and Drosophila sperm, are unique in that the axoneme is exposed to the cytoplasm. Fingerhut and Yamashita show that localization of a novel RNP granule containing axonemal dynein mRNAs facilitates incorporation of these axonemal proteins, promoting cytoplasmic cilia formation., Cytoplasmic cilia, a specialized type of cilia in which the axoneme resides within the cytoplasm rather than within the ciliary compartment, are proposed to allow for the efficient assembly of very long cilia. Despite being found diversely in male gametes (e.g., Plasmodium falciparum microgametocytes and human and Drosophila melanogaster sperm), very little is known about cytoplasmic cilia assembly. Here, we show that a novel RNP granule containing the mRNAs for axonemal dynein motor proteins becomes highly polarized to the distal end of the cilia during cytoplasmic ciliogenesis in Drosophila sperm. This allows for the incorporation of these axonemal dyneins into the axoneme directly from the cytoplasm, possibly by localizing translation. We found that this RNP granule contains the proteins Reptin and Pontin, loss of which perturbs granule formation and prevents incorporation of the axonemal dyneins, leading to sterility. We propose that cytoplasmic cilia assembly requires the precise localization of mRNAs encoding key axonemal constituents, allowing these proteins to incorporate efficiently into the axoneme.

Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here, we show that Alms1a, a Drosophila homolog of the human ciliopathy gene Alstrom syndrome, is enriched on the mother centrosome in Drosophila male germline stem cells (GSCs). Depletion of alms1a in GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication, suggesting that Alms1a has a stem-cell-specific function in centrosome duplication. Alms1a interacts with Sak/Plk4, a critical regulator of centriole duplication, more strongly at the GSC mother centrosome, further supporting Alms1a’s unique role in GSCs. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.

Cytoplasmic cilia, a specialized type of cilia in which the axoneme resides within the cytoplasm rather than within the ciliary compartment, are proposed to allow the efficient assembly of very long cilia. Despite being found diversely in male gametes (e.g. Plasmodium microgametocytes and human and Drosophila sperm), very little is known about cytoplasmic cilia assembly. Here we show that a novel RNP granule containing the mRNAs for axonemal dynein motor proteins becomes highly polarized to the distal end of the cilia during cytoplasmic ciliogenesis in Drosophila sperm. This allows for the localized translation of these axonemal dyneins and their incorporation into the axoneme directly from the cytoplasm. We found that this RNP granule contains the proteins Reptin and Pontin, loss of which perturbs granule formation and prevents incorporation of the axonemal dyneins, leading to sterility. We propose that cytoplasmic cilia require the local translation of key protein constituents such that these proteins are incorporated efficiently into the axoneme.Author SummaryCytoplasmic cilia, which are found in human and Drosophila sperm, are unique in that the axoneme is exposed to the cytoplasm. The authors show that a novel RNP granule containing axonemal dynein mRNAs facilitates localized translation of these axonemal proteins, facilitating cytoplasmic cilia formation.

To assess whether the hop-derived polyphenol isoxanthohumol suppresses insulin resistance by changing the intestinal microbiota.Male C57BL/6J mice (7 weeks of age) were divided into five groups (n = 9-10): Normal Diet (ND), High Fat Diet (HFD), HFD + low dose isoxanthohumol (0.01%IX), HFD + medium dose isoxanthohumol (0.03% IX), and HFD + high dose isoxanthohumol (0.1% IX). Oral glucose tolerance tests (OGTTs) were performed at 4 and 8 weeks, and insulin tolerance tests (ITTs) were performed at 13 weeks. 16S rRNA gene sequencing analyses revealed the fecal microbiota profiles, and the relative abundance of Akkermansia muciniphila and Clostridium cluster XI was calculated by qRT-PCR. Plasma lipopolysaccharide (LPS) levels were measured by ELISA, and mRNA expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in epididymal adipose tissues were measured by qRT-PCR.Isoxanthohumol showed antibacterial activity towards several bacterial species and mitigated impaired glucose tolerance and insulin resistance induced by the HFD in a dose-dependent manner, as shown by OGTTs and ITTs. The concentration of phylum Verrucomicrobia bacteria dramatically increased in the 0.1% IX group, the relative abundance of A. muciniphila increased, and that of Clostridium cluster XI decreased. Moreover, the intake of isoxanthohumol decreased the levels of plasma LPS and mRNA expression of TNF-α and IL-1β in epididymal adipose tissues.We found that isoxanthohumol can suppress HFD-induced insulin resistance by changing the intestinal microbiota and reducing the expression of inflammation factors.

GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs.

The use of microorganisms in agriculture such as Azospirillum brasilense and the cultivation of cover crops in the off season, together with nitrogen fertilization, may be interesting alternatives to increase crop yield. The objective of this study was to evaluate the growth, production and nitrogen concentration of maize grown in succession to cover crops and their interactions with A. brasilense inoculation and topdressing mineral N fertilization. The experiment was conducted on Oxisol, in randomized block design in split-split-plot scheme with four repetitions. The plots consisted of four cover crops: jackbean (Canavalia ensiformis), dwarf pigeon pea (Cajanus cajan), crotalaria (Crotalaria spectabilis) and spontaneous vegetation. In the subplots, with or without inoculation of A. brasilense in maize seeds, and in the sub-subplots: with or without topdressing N fertilization. It was verified that jackbean can generate increments of up to 8.3% in grains per ear, 6.9% in length of ear and 15.2% in mass of one hundred grains. Consequently, the grain yield was higher in this treatment (18%). The inoculation with A. brasilense and topdressing N fertilization did not generate significant increments in maize production components, as observed for cover crops. RESUMO O uso de microrganismos na agricultura como Azospirillum brasilense e o cultivo de plantas de cobertura na entressafra, juntamente com a adubação nitrogenada, podem ser alternativas interessantes para aumentar a produtividade das culturas. Este estudo teve por objetivo avaliar os componentes de crescimento e de produção e o teor de nitrogênio do milho cultivado em sucessão ao cultivo de plantas de cobertura e suas interações com a inoculação de A. brasilense e a adubação mineral de N em cobertura. O experimento foi conduzido em Latossolo Vermelho-Amarelo no delineamento de blocos casualizados em parcelas sub-subdivididas com quatro repetições. As parcelas foram constituídas por quatro plantas de cobertura: feijão-de-porco (Canavalia ensiformis), feijão guandu anão (Cajanus cajan), crotalária (Crotalaria spectabilis) e vegetação espontânea. Nas subparcelas, com ou sem inoculação de A. brasilense nas sementes de milho e, nas sub-subparcelas: com ou sem adubação nitrogenada em cobertura. Verificou-se que o feijão-de-porco pode gerar incrementos de até 8,3% em grãos por espiga, 6,9% em comprimento de espiga e 15,2% em massa de cem grãos. Consequentemente, a produtividade de grãos foi maior neste tratamento (18%). A inoculação com A. brasilense e a adubação nitrogenada em cobertura não geraram incrementos significativos nos componentes produtivos do milho, como observado para plantas de cobertura.

Divalent europium(II)-doped mesoporous silicon oxy-nitride materials, as a novel type of nanoscopic photoluminescent material, are studied in which the optically active luminescent centers are isolated within the pores. Colorless and transparent blue emitting luminous Eu2+-doped mesoporous silicon oxy-nitride materials were prepared from mesoporous silica via impregnation, nanocasting and nitrogen-assisted carbothermal reduction and nitridation method. The morphology and porosity of the silica remain unchanged during the synthesis process as revealed by SEM images and by nitrogen sorption studies. Photoluminescence studies reveal a strong blue emission band for Eu2+ centered at 425 nm with a quantum efficiency of 47%. The luminescent intensity is greatly influenced by the amount of co-dopant, Al3+ ions.

Gametes, eggs and sperm, are the highly specialized cell types on which the development of new life solely depends. Although all cells share essential organelles, such as the ER (endoplasmic reticulum), Golgi, mitochondria, and centrosomes, germ cells display unique regulation and behavior of organelles during gametogenesis. These germ cell-specific functions of organelles serve critical roles in successful gamete production. In this chapter, I will review the behaviors and roles of organelles during germ cell differentiation.

Objective To evaluate the classification statistics of the Clinical Assessment of Attention Deficit – Adult (CAT-A) Negative Impression (NI) scale, relative to the MMPI-2-RF in an active duty military sample. We hypothesized that MMPI-2-RF RBS would have the largest AUC. Method Retrospective review of 108 active duty service members consecutively referred to neuropsychology for clinical ADHD evaluations in a Midwest Army Health Center. Cases with missing data (10) and failures of MMPI-2-RF response consistency scales (3) were removed from analysis, resulting in final sample of 95. Average age was 32.62 (SD = 8.87) and average education was 14.66 (SD = 2.66). MMPI-2-RF symptom validity scales (F-r, Fp-r, Fs, FBS-r, and RBS) were employed as criterion measures at all standard cut-offs to evaluate the CAT-A NI scale. Results ROC analyses for the MMPI-2-RF over-reporting symptom validity scales ranged from 0.599 to 0.808, with the MMPI-2-RF RBS scale >79 demonstrating the lowest AUC (0.599; p 52. With specificity held at or above 0.90, sensitivities ranged from 22.86 to 60.00, with positive and negative predictive values ranging from 11.1 to 58.8 and 66.7 to 98.8, respectively. Conclusions The CAT-A NI scale demonstrated reasonable AUC values for nearly all MMPI-2-RF over-reporting scales. Psychologically-based over-reporting scales were superior to cognitively-based over-reporting scales in terms of classification statistics. The optimal cut in the current data (>52) is slightly higher (though roughly commensurate) to the cut score for atypical responses in the CAT-A manual (>45).

Satellite DNAs are highly repetitive sequences that account for the majority of constitutive heterochromatin in many eukaryotic genomes. It is widely recognized that sequences and locations of satellite DNAs are highly divergent even in closely related species, contributing to the hypothesis that satellite DNA differences may underlie speciation. However, due to its repetitive nature, the mapping of satellite DNAs has been mostly left out of recent genomics analyses, hampering the use of molecular genetics techniques to better understand their role in speciation and evolution. Satellite DNAs are most extensively and comprehensively mapped in Drosophila melanogaster, a species that is also an excellent model system with which to study speciation. Yet the lack of comprehensive knowledge regarding satellite DNA identity and location in its sibling species (D. simulans, D. mauritiana, and D. sechellia) has prevented the full utilization of D. melanogaster in studying speciation. To overcome this problem, we initiated the mapping of satellite DNAs on the genomes of the D. melanogaster species complex (D. melanogaster, D. simulans, D. mauritiana, and D. sechellia) using multi-color fluorescent in situ hybridization (FISH) probes. Our study confirms a striking divergence of satellite DNAs in the D. melanogaster species complex, even among the closely related species of the D. simulans clade (D. simulans, D. mauritiana, and D. sechellia), and suggests the presence of unidentified satellite sequences in these species.

Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic. We used the elevated T-maze model and Vogel conflict test to evaluate defensive responses associated with anxiety or panic. The results showed that intra-PL PIC caused an increase in c-Fos activation in serotonergic cells in DR subregions. Furthermore, the intra-PL injection of PIC induced a panicolytic-like effect without affecting behaviors associated with anxiety. Our findings suggest that the PL-DR pathway, through DR serotonergic stimulation, is involved in the control of panic-related behaviors by control of serotonin release in structures that modulate panic responses, such as the dorsal periaqueductal gray.

This work was also supported by the National Science Centre , Poland under grant number 2017/25/B/ST2/00901. We combined different experimental techniques with a theoretical approach to determine a consistent set of diagram lines energies and binding energies. We propose an original approach consisting in determining the mass attenuation coefficients in an energy range covering the L-, M- and N- absorption edges, including a detailed evaluation of the associated uncertainties, to derive precisely the binding energies. We investigated the Lα, Lβ and M spectra of Gd with an independantly calibrated high-resolution anti-parallel double-crystal x-ray spectrometer. All the lines were identified and found in excellent agreement with the binding energies previously derived. Morever, we identified for the first time M5−O2, M4−O2,3 and M4−N2,3 diagram lines. authorsversion published

Intracranial abscess is a rare but life-threatening disease. There have been no reports on intracranial abscess induced by the residual primary tooth and the impacted successive permanent tooth with infection. We report on an interesting case of a 29-year-old man suffering from an epidural abscess, potentially caused by an infection of the residual primary maxillary right canine and the impacted permanent maxillary right canine. The patient recovered completely after prolonged antibiotic treatment and extraction of both of the suspected teeth. Fusobacterium sp. was isolated from the culture of a peripheral blood sample. This case alerts us to realize that the lack of suitable and timely intervention in oral conditions might produce a harmful effect on general health.

Fear is an emotion that serves as a driving factor in how organisms move through the world. In this review, we discuss the current understandings of the subjective experience of fear and the related biological processes involved in fear learning and memory. We first provide an overview of fear learning and memory in humans and animal models, encompassing the neurocircuitry and molecular mechanisms, the influence of genetic and environmental factors, and how fear learning paradigms have contributed to treatments for fear-related disorders, such as posttraumatic stress disorder. Current treatments as well as novel strategies, such as targeting the perisynaptic environment and use of virtual reality, are addressed. We review research on the subjective experience of fear and the role of autobiographical memory in fear-related disorders. We also discuss the gaps in our understanding of fear learning and memory, and the degree of consensus in the field. Lastly, the development of linguistic tools for assessments and treatment of fear learning and memory disorders is discussed.

In eukaryotic genomes, ribosomal RNA (rRNA) genes exist as tandemly repeated clusters, forming ribosomal DNA (rDNA) loci. Each rDNA locus typically contains hundreds of rRNA genes to meet the high demand of ribosome biogenesis. Nucleolar dominance is a phenomenon whereby individual rDNA loci are entirely silenced or transcribed, and is believed to be a mechanism to control rRNA dosage. Nucleolar dominance was originally noted to occur in interspecies hybrids, and has been shown to occur within a species (i.e., nonhybrid context). However, studying nucleolar dominance within a species has been challenging due to the highly homogenous sequence across rDNA loci. By utilizing single nucleotide polymorphisms between X rDNA and Y rDNA loci in males, as well as sequence variations between two X rDNA loci in females, we conducted a thorough characterization of nucleolar dominance throughout development of Drosophila melanogaster. We demonstrate that nucleolar dominance is a developmentally regulated program that occurs in nonhybrid, wild-type D. melanogaster, where Y rDNA dominance is established during male embryogenesis, whereas females normally do not exhibit dominance between two X rDNA loci. By utilizing various chromosomal complements (e.g., X/Y, X/X, X/X/Y) and a chromosome rearrangement, we show that the short arm of the Y chromosome including the Y rDNA likely contains information that instructs the state of nucleolar dominance. Our study begins to reveal the mechanisms underlying the selection of rDNA loci for activation/silencing in nucleolar dominance in the context of nonhybrid D. melanogaster.

In many species, germline stem cells (GSCs) function to sustain gametogenesis throughout the life of organismal life span. As the source of gametes, the only cell type that can pass the genetic information to the next generation, GSCs play a fundamental role in maximizing the quantity of gametes that animals produce, while ensuring their highest quality. GSCs are maintained by the signals from their niches, and germ cells that exited the niche undergo differentiation to generate functional gametes. GSC population is sustained by a multitude of mechanisms such as asymmetric stem cell divisions and dedifferentiation of partially differentiated germ cells. In this review, we summarize the mechanisms that maintain GSC homeostasis to ensure life-long production of functional gametes.

Gasoline Particulate Filters (GPF) are one of the primary technologies which are able to effectively reduce particulate number (PN) emissions from Gasoline Direct Injection (GDI) vehicles. Due to increasingly stringent global emission requirements as well as the implementation of Real Driving Emission (RDE) testing conditions, it is critical to continuously develop and improve GPF performance.

Background: Serotonin plays an important role in the regulation of anxiety, acting through complex modulatory mechanisms within distinct brain structures. Serotonin can act through complex negative feedback mechanisms controlling the neuronal activity of serotonergic circuits and downstream physiologic and behavioral responses. Administration of serotonin or the serotonin 1A receptor agonist, (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT), into the prefrontal cortex, inhibits anxiety-like responses. The prelimbic area of the prefrontal cortex regulates serotonergic neurons within the dorsal raphe nucleus and is involved in modulating anxiety-like behavioral responses. Aims: This study aimed to investigate the serotonergic role within the prelimbic area on anxiety- and panic-related defensive behavioral responses. Methods: We investigated the effects of serotonin within the prelimbic area on inhibitory avoidance and escape behaviors in the elevated T-maze. We also extended the investigation to serotonin 1A, 2A, and 2C receptors. Results: Intra-prelimbic area injection of serotonin or 8-OH-DPAT induced anxiolytic effects without affecting escape behaviors. Previous administration of the serotonin 1A receptor antagonist, WAY-100635, into the prelimbic area counteracted the anxiolytic effects of serotonin. Neither the serotonin 2A nor the serotonin 2C receptor preferential agonists, (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212), respectively, affected behavioral responses in the elevated T-maze. Conclusion: Facilitation of serotonergic signaling within the prelimbic area of rats induced an anxiolytic effect in the elevated T-maze test, which was mediated by local serotonin 1A receptors. This inhibition of anxiety-like defensive behavioral responses may be mediated by prelimbic area projections to neural systems controlling anxiety, such as the dorsal raphe nucleus or basolateral amygdala.

Although considered to be exact copies of each other, sister chromatids can segregate non-randomly in some cases. For example, sister chromatids of the X and Y chromosomes segregate non-randomly during asymmetric division of male germline stem cells (GSCs) in D. melanogaster. Here we identify that the ribosomal DNA (rDNA) loci, which are located on the X and Y chromosomes, and an rDNA-binding protein, Indra, are required for non-random sister chromatid segregation (NRSS). We provide the evidence that NRSS is a mechanism by which GSCs recover rDNA copy number, which occurs through unequal sister chromatid exchange, counteracting the spontaneous copy number loss that occurs during aging. Our study reveals an unexpected role for NRSS in maintaining germline immortality through maintenance of a vulnerable genomic element, rDNA.One Sentence SummaryrDNA copy number maintenance by non-random sister chromatid segregation contributes to germline immortality in Drosophila

A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. In our previous study (Jagannathan et al., 2018), we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus. Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a ‘modular’ network, where interactions between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that interactions between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.

The piRNA pathway protects germline genomes through transcript cleavage of selfish genetic elements, such as transposons, in the cytoplasm and their transcriptional silencing in the nucleus. Here, we describe a mechanism by which the nuclear and cytoplasmic arms of the silencing mechanism are linked. During mitosis ofDrosophilaspermatogonia, nuclear Piwi interacts with nuage, the compartment that mediates the cytoplasmic arm of piRNA-mediated silencing. At the end of mitosis, Piwi leaves nuage to return to the nucleus. We found that dissociation of Piwi from nuage occurs at the depolymerizing microtubules of the central spindle, mediated by a microtubule-depolymerizing kinesin Klp10A. Depletion ofklp10Adelays Piwi’s return to the nucleus and affects piRNA production, suggesting the importance of nuclear-cytoplasmic communication in piRNA biogenesis. We propose that cell cycle-dependent communication between the nuclear and cytoplasmic arms of the piRNA pathway plays important roles in coordinated piRNA production.

Adult stem cells reside in specialized microenvironments, called niches, that maintain stem cells in an undifferentiated and self-renewing state. Defining and understanding the mechanisms that restrict niche signaling exclusively to stem cells is crucial to determine how stem cells undergo self-renewal while their progeny, often located just one cell diameter away from the niche, differentiate. Despite extensive studies on the signaling pathways that operate within stem cells and their niches, how this segregation occurs remains elusive. Here we review recent progress on the characterization of niche-stem cell interactions, with a focus on emerging mechanisms that spatially restrict niche signaling. Mol. Reprod. Dev. 83: 675-683, 2016 © 2016 Wiley Periodicals, Inc.

The hygiene or "Old Friends" hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these Old Friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here, we review recent advances in our understanding of the potential for Old Friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially derived metabolites, bacterial antigens, and helminthic antigens, through which these inputs promote immunoregulation. Though findings are encouraging, significant human subjects' research is required to evaluate the potential impact of Old Friends, including environmental microbial inputs, on biological signatures and clinically meaningful mental health prevention and intervention outcomes.

PURPOSE To investigate the relationship between the change of daily step counts and low back pain (LBP) during pregnancy. Materials and METHODS Pregnant women at less than eight weeks of gestation (WG) were recruited. Daily step counts were measured with a pedometer. To assess LBP, the Oswestry disability index (ODI) score was recorded. Thirty-six individuals were divided into the LBP and non-LBP groups. The effect of step counts on LBP between the two groups was analyzed. RESULTS At 16-19 WG, step counts were not considerably changed in the non-LBP group but were significantly increased in the LBP group. At 24-27 and 32-35 WG, step counts were increased in the non-LBP group but were significantly decreased in the LBP group. CONCLUSIONS Acute increase of daily step counts in early pregnancy is a risk for LBP, and gradual increases of step counts after mid-pregnancy is recommended for women.

Background and Objectives We evaluated the phenotypic and functional distinction between B cells with receptors for human blood group A and B determinants in α-galactosyltransferase-deficient (GalT−/−) mice. Materials and Methods GalT−/− mice were immunized with human blood group A or B red blood cells (RBCs), and the anti-A or B anti-bodies (Abs) were determined in their sera. B cells with receptors for group A and B epitopes were identified by the use of synthetic A and B determinants. Results The anti-A and anti-B Ab levels were comparably elevated in the sera of GalT−/− mice after the immunization with A/B-RBCs. B cells bearing receptors recognizing B epitopes exhibited the CD5dim/− CD11b+ B-1b-cell phenotype, whereas those with receptors for A epitopes showed the CD5+CD11b+ B-1a-cell phenotype. Myeloid differentiation factor 88 (MyD88) levels increased in B cells with anti-B receptors, indicating a contribution of Toll-like receptor (TLR) signalling, whereas no such elevation was detected in B cells with anti-A receptors. Calcineurin inhibitor (CNI) treatment prevented the elevation of anti-A Ab levels after immunization, but did not affect anti-B Ab levels. Conclusions These findings indicate different sensitivities of B cells with blood group A and B antigens in the response to CNIs.