State transition is quiet around pyrenoid and LHCII phosphorylation is not essential for thylakoid deformation in Chlamydomonas 137c.

Photosynthetic organisms have developed a regulation mechanism called state transition (ST) to rapidly adjust the excitation balance between the two photosystems by light-harvesting complex II (LHCII) movement. Though many researchers have assumed coupling of the dynamic transformations of the thylakoid membrane with ST, evidence of that remains elusive. To clarify the above-mentioned coupling in a model organism Chlamydomonas, here we used two advanced microscope techniques, the excitation-spectral microscope (ESM) developed recently by us and the superresolution imaging based on structured-illumination microscopy (SIM). The ESM observation revealed ST-dependent spectral changes upon repeated ST inductions. Surprisingly, it clarified a less significant ST occurrence in the region surrounding the pyrenoid, which is a subcellular compartment specialized for the carbon-fixation reaction, than that in the other domains. Further, we found a species dependence of this phenomenon: 137c strain showed the significant intracellular inhomogeneity of ST occurrence, whereas 4A+ strain hardly did. On the other hand, the SIM observation resolved partially irreversible fine thylakoid transformations caused by the ST-inducing illumination. This fine, irreversible thylakoid transformation was also observed in the STT7 kinase-lacking mutant. This result revealed that the fine thylakoid transformation is not induced solely by the LHCII phosphorylation, suggesting the highly susceptible nature of the thylakoid ultrastructure to the photosynthetic light reactions.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone.

In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches-the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of Hdac8 in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.

Dominant-negative variants in CBX1 cause a neurodevelopmental disorder.

PURPOSE: This study aimed to establish variants in CBX1, encoding heterochromatin protein 1ß (HP1ß), as a cause of a novel syndromic neurodevelopmental disorder. METHODS: Patients with CBX1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient. To investigate the pathogenicity of identified variants, we performed in vitro cellular assays and neurobehavioral and cytological analyses of neuronal cells obtained from newly generated Cbx1 mutant mouse lines. RESULTS: In 3 unrelated individuals with developmental delay, hypotonia, and autistic features, we identified heterozygous de novo variants in CBX1. The identified variants were in the chromodomain, the functional domain of HP1ß, which mediates interactions with chromatin. Cbx1 chromodomain mutant mice displayed increased latency-to-peak response, suggesting the possibility of synaptic delay or myelination deficits. Cytological and chromatin immunoprecipitation experiments confirmed the reduction of mutant HP1ß binding to heterochromatin, whereas HP1ß interactome analysis demonstrated that the majority of HP1ß-interacting proteins remained unchanged between the wild-type and mutant HP1ß. CONCLUSION: These collective findings confirm the role of CBX1 in developmental disabilities through the disruption of HP1ß chromatin binding during neurocognitive development. Because HP1ß forms homodimers and heterodimers, mutant HP1ß likely sequesters wild-type HP1ß and other HP1 proteins, exerting dominant-negative effects.

Menstrual Status and Pregnancy in Former Elite Long-Distance Runners With Menstrual Disorders.

OBJECTIVE: To estimate the ratio of menstrual abnormalities, infertility, and other problems related to pregnancy and childbirth in former long-distance runners. We hypothesized that the female athlete triad during an athletic career affects future fertility and childbearing in former athletes. DESIGN: Cross-sectional study. SETTING: Participants of the All Japan University Women's Ekiden. PARTICIPANTS: Female former athletes who competed at national level were asked to complete the questionnaire; 137 valid responses were obtained. INDEPENDENT VARIABLES: Age at menarche and at the onset of pregnancy, history of amenorrhea and gynecological disorders, and lowest body mass index (BMI) during their athletic career. MAIN OUTCOME MEASURES: Menstrual status, history of pregnancy and childbirth, any related infertility treatment and problems, and history of stress fractures. RESULTS: The mean age at menarche was 13.3 ± 2.2 (range, 10-25) years. Five athletes (3.6%) had primary amenorrhea. Eleven of the 137 participants (8.0%) required treatment for infertility. Sixty participants had 121 pregnancies, of which 5 were yet to deliver during the survey. Fifteen of 116 pregnancies (12.9%) ended in miscarriage, induced abortion, or stillbirth. Logistic regression analysis showed that the factors related to "infertility treatment" were age at the onset of pregnancy ( P = 0.047) and higher BMI during their athletic career ( P = 0.032; odds ratio, 2.19). CONCLUSIONS: The main factor influencing infertility was an older age at the time of pregnancy, similar to that observed in the general population. Amenorrhea or being underweight during their athletic career was not associated with problems related to conception and childbirth.

Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

An Open Soil Health Assessment Framework Facilitating Sustainable Soil Management.

The crucial role of healthy soil in achieving sustainable food production and environment is increasingly recognized, as is the importance of proper assessment of soil quality. We introduce a new framework, open soil index (OSI), which integrally evaluates soil health of agricultural fields and provides recommendation for farming practices. The OSI is an open-source modular framework in which soil properties, functions, indicators and scores, and management advice are linked hierarchically. Soil health is evaluated with respect to sustainable crop production but can be extended to other ecosystem functions. The OSI leverages the existing knowledge base of agronomic research and routine laboratory data, enabling its application with limited cost. The OSI is a generic framework that can be adopted for specific regions with specific objectives. As a proof of concept, the OSI is implemented for all (>700,000) Dutch agricultural fields and illustrated with 11 pairs ("good" and "poor") of local fields and 32 fields where soil quality and crop yield have been monitored. The OSI produced reasonable evaluation for most pairs when soil physical functions were refined with on-site soil visual assessment. The soil functions are sufficiently independent and yet together reflect complex multidimensionality of soil quality. The framework can facilitate designing sustainable soil management programs by bridging regional targets to field-level actions.

Mechanisms and significance of microglia-axon interactions in physiological and pathophysiological conditions.

Microglia are the resident immune cells of the central nervous system, and are important for cellular processes. In addition to their classical roles in pathophysiological conditions, these immune cells also dynamically interact with neurons and influence their structure and function in physiological conditions. Microglia have been shown to contact neurons at various points, including the dendrites, cell bodies, synapses, and axons, and support various developmental functions, such as neuronal survival, axon elongation, and maturation of the synaptic circuit. This review summarizes the current knowledge regarding the roles of microglia in brain development, with particular emphasis on microglia-axon interactions. We will review recent findings regarding the functions and signaling pathways involved in the reciprocal interactions between microglia and neurons. Moreover, as these interactions are altered in disease and injury conditions, we also discuss the effect and alteration of microglia-axon interactions in disease progression and the potential role of microglia in developmental brain disorders.

Attitude toward breakfast mediates the associations of wake time and appetite for breakfast with frequency of eating breakfast.

PURPOSE: We investigated associations among attitude toward breakfast, appetite for breakfast, wake time, personality traits, self-esteem, and frequency of eating breakfast in university students and proposed a model of factors affecting the frequency of eating breakfast. METHODS: The participants, 555 Japanese university students (177 men, 378 women), completed a questionnaire about their height and weight, living with family, wake time, frequency of eating breakfast, appetite for breakfast, attitude toward breakfast, personality traits, and self-esteem. Appetite for breakfast was evaluated with a four-point Likert-type scale. Attitude toward breakfast was assessed with a 13-item questionnaire using a five-point Likert-type scale; responses to the items were summed, and divided by the number of items to produce a score. RESULTS: Multiple linear regression analysis showed that frequency of eating breakfast was positively associated with appetite for breakfast and attitude toward breakfast, and inversely associated with wake time. Wake time was inversely associated with attitude toward breakfast, and appetite for breakfast was positively associated with attitude toward breakfast. Structural equation modeling showed that the structured model based on the multiple regression analysis was a good fit for both men (chi-square value to the degrees of freedom [χ2/df] = 1.096, root mean square error of approximation [RMSEA] = 0.023) and women (χ2/df = 1.510, RMSEA = 0.037). CONCLUSIONS: These results suggest that wake time and appetite for breakfast are directly associated with frequency of eating breakfast. Attitude toward breakfast mediates the indirect association between frequency of eating breakfast and both wake time and appetite for breakfast. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

High-Speed Excitation-Spectral Microscopy Uncovers In Situ Rearrangement of Light-Harvesting Apparatus in Chlamydomonas during State Transitions at Submicron Precision.

Photosynthetic organisms adjust to fluctuating natural light under physiological ambient conditions through flexible light-harvesting ability of light-harvesting complex II (LHCII). A process called state transition is an efficient regulation mechanism to balance the excitations between photosystem II (PSII) and photosystem I (PSI) by shuttling mobile LHCII between them. However, in situ observation of the migration of LHCII in vivo remains limited. In this study, we investigated the in vivo reversible changes in the intracellular distribution of the chlorophyll (Chl) fluorescence during the light-induced state transitions in Chlamydomonas reinhardtii. The newly developed noninvasive excitation-spectral microscope provided powerful spectral information about excitation-energy transfer between Chl-a and Chl-b. The excitation spectra were detected through the fluorescence emission in the 700-750-nm spectral range, where PSII makes the main contribution, though PSI still makes a non-negligible contribution at room temperature. The technique is sensitive to the Chl-b spectral component specifically bound to LHCII. Using a PSI-specific 685-nm component also provided visualization of the local relative concentration of PSI within a chloroplast at room temperature. The decrease in the relative intensity of the Chl-b band in state 2 was more conspicuous in the PSII-rich region than in the PSI-rich region, reflecting the dissociation of LHCII from PSII. We observed intracellular redistributions of the Chl-b-related light-harvesting abilities within a chloroplast during the state transitions. This observation implies the association of the state transitions with the morphological changes in the thylakoid membrane.

Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1) and auxarconjugatin-B (2)) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC50 of 0.27 µM in CCRF-CEM cells, while it did not affect Burkitt lymphoma-derived cell line Raji and the cervical cancer cell line HeLa, or the oral cancer cell line HSC-3 (IC50 > 10 µM). This compound will be a promising compound for developing T-ALL-specific drugs.

Long-term survival rate of closing wedge high tibial osteotomy with high valgus correction: a 15-year follow-up study.

PURPOSE: The influence of closing wedge high tibial osteotomy (CW-HTO) with high valgus correction on its survival is unclear. This study aimed to conduct a 15-year follow-up cohort study to estimate the long-term survival rate of CW-HTO. Factors related to poor outcomes were investigated. METHODS: A total of 159 knees in 123 patients were followed up, and 120 knees in 96 patients were enrolled for statistical analysis. Femorotibial angles were measured by standing anterior-posterior radiographs of the knee. Clinical objective evaluation was performed by the Japanese orthopaedic association (JOA) score of the knee, and scores lower than 70 points defined the poor result (PR) group. The survival rate of OW-HTO was estimated. Logistic regression analyses were performed to determine the risk factors for PR and conversion to total knee arthroplasty (TKA). RESULTS: A total of 16 knees in 15 patients (13.3%) underwent TKA 14.0 ± 4.8 (4-20) years after CW-HTO. The 5-year survival rate was 99.2%, 10-year was 96.7%, 15-year was 92.5%, and 86.7% at final follow-up (17.9 years). Based on the JOA score, 44 patients (35.8%) belonged to the PR group, and their risk factors were obesity (p = 0.018), low femorotibial angle (p = 0.019), low JOA score (p = 0.040), low knee extension angle (p = 0.045), and low knee flexion angle (p = 0.046). CONCLUSIONS: The 15-year survival rate of CW-HTO was 92.5%. While higher scores of objective outcomes were kept over long-term follow-up, the risk factors for a worsening score or TKA conversion were obesity and severity of preoperative knee symptoms.

Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method.

BACKGROUND: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). METHOD: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. RESULTS: The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. CONCLUSION: DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies.

Associations between trunk-to-peripheral fat ratio and cardiometabolic risk factors in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Body mass-independent parameters might be more appropriate for assessing cardiometabolic abnormalities than weight-dependent indices in Asians who have relatively high visceral adiposity but low body fat. Dual-energy X-ray absorptiometry (DXA)-measured trunk-to-peripheral fat ratio is one such body mass-independent index. However, there are no reports on relationships between DXA-measured regional fat ratio and cardiometabolic risk factors targeting elderly Asian men. METHODS: We analyzed cross-sectional data of 597 elderly men who participated in the baseline survey of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study, a community-based single-center prospective cohort study conducted in Japan. Whole-body fat and regional fat were measured with a DXA scanner. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: Both TAR and TLR in the group of men who used ≥ 1 medication for hypertension, dyslipidemia, or diabetes ("user group"; N = 347) were significantly larger than those who did not use such medication ("non-user group"; N = 250) (P < 0.05). After adjusting for potential confounding factors including whole-body fat, both TAR and TLR were significantly associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting serum insulin, and the insulin resistance index in the non-user group and non-overweight men in the non-user group (N = 199). CONCLUSION: The trunk-to-peripheral fat ratio was associated with cardiometabolic risk factors independently of whole-body fat mass. Parameters of the fat ratio may be useful for assessing cardiometabolic risk factors, particularly in underweight to normal-weight populations.

Determinants of bone health in elderly Japanese men: study design and key findings of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study.

BACKGROUND: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study was launched to investigate risk factors for osteoporotic fractures, interactions of osteoporosis with other non-communicable chronic diseases, and effects of fracture on QOL and mortality. METHODS: FORMEN baseline study participants (in 2007 and 2008) included 2012 community-dwelling men (aged 65-93 years) in Nara prefecture, Japan. Clinical follow-up surveys were conducted 5 and 10 years after the baseline survey, and 1539 and 906 men completed them, respectively. Supplemental mail, telephone, and visit surveys were conducted with non-participants to obtain outcome information. Survival and fracture outcomes were determined for 2006 men, with 566 deaths identified and 1233 men remaining in the cohort at 10-year follow-up. COMMENTS: The baseline survey covered a wide range of bone health-related indices including bone mineral density, trabecular microarchitecture assessment, vertebral imaging for detecting vertebral fractures, and biochemical markers of bone turnover, as well as comprehensive geriatric assessment items. Follow-up surveys were conducted to obtain outcomes including osteoporotic fracture, cardiovascular diseases, initiation of long-term care, and mortality. A complete list of publications relating to the FORMEN study can be found at https://www.med.kindai.ac.jp/pubheal/FORMEN/Publications.html .

[A Case of Lymphoepithelioma-Like Carcinoma of the Ureter].

Lymphoepithelioma-like carcinoma (LELC) of the ureter is very rare and only 14 previous cases have been reported. Here, we report a case of LELC of the ureter. A 76-year-old woman was admitted to our hospital complaining of gross hematuria. Left ureteral cancer was suspected by the imaging examination, and laparoscopic left total nephroureterectomy was performed. Histopathological examination showed pure type of LELC in the ureter. She is alive without disease recurrence at fifteen months after surgery.

Increased Expression of Fibronectin Leucine-Rich Transmembrane Protein 3 in the Dorsal Root Ganglion Induces Neuropathic Pain in Rats.

Neuropathic pain is a chronic condition that occurs frequently after nerve injury and induces hypersensitivity or allodynia characterized by aberrant neuronal excitability in the spinal cord dorsal horn. Fibronectin leucine-rich transmembrane protein 3 (FLRT3) is a modulator of neurite outgrowth, axon pathfinding, and cell adhesion, which is upregulated in the dorsal horn following peripheral nerve injury. However, the function of FLRT3 in adults remains unknown. Therefore, we aimed to investigate the involvement of spinal FLRT3 in neuropathic pain using rodent models. In the dorsal horns of male rats, FLRT3 protein levels increased at day 4 after peripheral nerve injury. In the DRG, FLRT3 was expressed in activating transcription factor 3-positive, injured sensory neurons. Peripheral nerve injury stimulated Flrt3 transcription in the DRG but not in the spinal cord. Intrathecal administration of FLRT3 protein to naive rats induced mechanical allodynia and GluN2B phosphorylation in the spinal cord. DRG-specific FLRT3 overexpression using adeno-associated virus also produced mechanical allodynia. Conversely, a function-blocking FLRT3 antibody attenuated mechanical allodynia after partial sciatic nerve ligation. Therefore, FLRT3 derived from injured DRG neurons increases dorsal horn excitability and induces mechanical allodynia.SIGNIFICANCE STATEMENT Neuropathic pain occurs frequently after nerve injury and is associated with abnormal neuronal excitability in the spinal cord. Fibronectin leucine-rich transmembrane protein 3 (FLRT3) regulates neurite outgrowth and cell adhesion. Here, nerve injury increased FLRT3 protein levels in the spinal cord dorsal root, despite the fact that Flrt3 transcripts were only induced in the DRG. FLRT3 protein injection into the rat spinal cord induced mechanical hypersensitivity, as did virus-mediated FLRT3 overexpression in DRG. Conversely, FLRT3 inhibition with antibodies attenuated mechanically induced pain after nerve damage. These findings suggest that FLRT3 is produced by injured DRG neurons and increases neuronal excitability in the dorsal horn, leading to pain sensitization. Neuropathic pain induction is a novel function of FLRT3.

Maternal pre-pregnancy underweight is associated with underweight and low bone mass in school-aged children.

INTRODUCTION: A number of studies have reported that pre-pregnancy overweight status is associated with offspring obesity, yet only a few studies have examined pre-pregnancy underweight status as it associates with offspring health. The aim of the present study was to assess the effect of pre-pregnancy underweight status in a mother on health outcomes in her offspring. To this end, the primary outcome examined in the present study was underweight status in the offspring, with a secondary outcome of offspring low bone mass. MATERIALS AND METHODS: The present retrospective cohort study, conducted from 2008 to 2011, targeted a source population of all students registered as fifth-graders at three public elementary schools in Hamamatsu and Fukuroi cities. Maternal height and weight before and after pregnancy and offspring weight and height at birth were obtained from the Maternal and Child Health Handbook. Offspring weight and height at age 10 years were measured using standard procedures. Offspring total body less head (TBLH) bone mineral content (BMC) was determined with a dual-energy X-ray absorptiometry scanner. RESULTS: Pre-pregnancy underweight status was found to be associated with an increased risk of an underweight status in female offspring (OR = 2.88, 95% CI 1.06-7.81). Offspring TBLH BMC in the underweight mother group was significantly lower than that in the non-underweight mother group. CONCLUSIONS: We determined that pre-pregnancy underweight status was more likely to lead to an underweight status and low TBLH BMC in school-aged offspring.

Low investment in sexual reproduction threatens plants adapted to phosphorus limitation.

Plant species diversity in Eurasian wetlands and grasslands depends not only on productivity but also on the relative availability of nutrients, particularly of nitrogen and phosphorus. Here we show that the impacts of nitrogen:phosphorus stoichiometry on plant species richness can be explained by selected plant life-history traits, notably by plant investments in growth versus reproduction. In 599 Eurasian sites with herbaceous vegetation we examined the relationship between the local nutrient conditions and community-mean life-history traits. We found that compared with plants in nitrogen-limited communities, plants in phosphorus-limited communities invest little in sexual reproduction (for example, less investment in seed, shorter flowering period, longer lifespan) and have conservative leaf economy traits (that is, a low specific leaf area and a high leaf dry-matter content). Endangered species were more frequent in phosphorus-limited ecosystems and they too invested little in sexual reproduction. The results provide new insight into how plant adaptations to nutrient conditions can drive the distribution of plant species in natural ecosystems and can account for the vulnerability of endangered species.

Trends in Serum Lipid Levels of a 10- and 13-Year-Old Population in Fukuroi City, Japan (2007-2017).

BACKGROUND: Current trends in serum lipid levels among children are likely to be important predictors of future cardiovascular disease prevalence. However, no studies have examined trends in low-density lipoprotein cholesterol (LDL-C) levels in Japanese children. METHODS: We investigated trends in LDL-C levels from 2008 through 2017 and HDL-C levels from 2007 through 2017 in a population of 10- and 13-year-old children in Fukuroi City, Japan. We analyzed 17,838 children, accounting for 93.8% of all fifth and eighth graders in the entire city. Adverse lipid levels were defined as follows: 130 mg/dL or higher for LDL-C, and lower than 40 mg/dL for HDL-C. The Jonckheere-Terpstra and Cochran-Armitage tests were used to evaluate secular trends in mean serum lipid levels and prevalence of dyslipidemia, respectively. RESULTS: There were no significant trends in BMI during the study period. In children aged 10 years, serum levels of LDL-C and HDL-C showed significant positive associations with calendar year during the study period for both sexes. A significant increase in HDL-C levels was observed in girls aged 13 years. On the other hand, no significant trends were observed in the prevalence of high LDL-C or low HDL-C regardless of sex or age, while the prevalence of high non-HDL-C showed a significant increase in boys. CONCLUSIONS: In the Fukuroi population, serum levels of LDL-C and HDL-C slightly increased in both boys and girls aged 10 years, and HDL-C levels slightly increased in girls aged 13 years, during the past decade.