Generating observation guided ensembles for data assimilation with denoising diffusion probabilistic model

This paper presents an ensemble data assimilation method using the pseudo ensembles generated by denoising diffusion probabilistic model. Since the model is trained against noisy and sparse observation data, this model can produce divergent ensembles close to observations. Thanks to the variance in generated ensembles, our proposed method displays better performance than the well-established ensemble data assimilation method when the simulation model is imperfect

Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro

<p>Abstract</p> <p>Background</p> <p>In 2005, Ghana replaced chloroquine with artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. The aim of this work was to determine for the first time, polymorphisms in the putative <it>pfATPase6 </it>and <it>pftctp</it>, <it>pfmdr1</it>, <it>pfcrt </it>genes in Ghanaian isolates, particularly at a time when there is no report on artemisinin resistance in malaria parasites from Ghana. The sensitivity of parasite isolates to anti-malaria drugs were also evaluated for a possible association with polymorphisms in these genes.</p> <p>Methods</p> <p>The prevalence of point mutations in the above <it>Plasmodium falciparum </it>genes were assessed from filter-paper blood blot samples by DNA sequencing. <it>In vitro </it>drug sensitivity test was carried out on some of the blood samples from volunteers visiting hospitals/clinics in southern Ghana using a modified version of the standard WHO Mark III micro-test.</p> <p>Results</p> <p>All successfully tested parasite isolates were sensitive to artesunate; while 19.4%, 29.0% and 51.6% were resistant to quinine, amodiaquine and chloroquine respectively. The geometric mean of IC₅₀value for artesunate was 0.73 nM (95% CI, 0.38-1.08), amodiaquine 30.69 nM (95% CI, 14.18-47.20) and chloroquine 58.73 nM (95% CI, 38.08-79.38). Twenty point mutations were observed in <it>pfATPase6 </it>gene, with no L263E and S769N. All mutations found were low in frequency, except D639G which was observed in about half of the isolates but was not associated with artesunate response (<it>p </it>= 0.42). The <it>pftctp </it>gene is highly conserved as no mutation was observed, while CVIET which is chloroquine-resistant genotype at codon 72-76 of the <it>pfcrt </it>gene was identified in about half of the isolates; this was consistent with chloroquine IC₅₀values (<it>p </it>= 0.001). Mutations were present in <it>pfmdr1 </it>gene but were not associated with artemisinin response (<it>p </it>= 1.00).</p> <p>Conclusion</p> <p>The <it>pfATPase6 </it>gene is highly polymorphic with D639G appearing to be fixed in Ghanaian isolates. These may just be spontaneous mutations as all parasite isolates that were tested displayed satisfactory <it>in vitro </it>response to artesunate. However, there is no improvement in susceptibility of the parasites to chloroquine five years after its proscription.</p

Establishment of a novel mouse xenograft model of human uterine leiomyoma

Uterine leiomyoma is the most common benign tumour in women, and an appropriate animal model for leiomyoma would be useful for exploring new therapeutic strategies. Therefore, we have been challenged to develop a new simple mouse model for human leiomyoma. Leiomyoma tissues were harvested from myomas resected by different surgical procedures with or without gonadotropin-releasing hormone agonist (GnRHa) treatment and were subcutaneously implanted into BALB/c nude mice with an estradiol/progesterone-releasing pellet. The implanted leiomyoma tissues that were obtained from the marginal site of large myomas resected by abdominal myomectomy with GnRHa treatment exhibited sufficient tumour growth in the transplanted mice. The leiomyomas that were treated with GnRHa highly expressed the estrogen/progesterone receptor genes, insulin-like growth factor 2 (IGF2) and embryonic smooth muscle myosin heavy chain (SMemb), which suggests that these factors are critical in the establishment of a mouse model of growing leiomyoma. As a result, this model will be useful for the development of new therapeutic strategies

Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow

骨髄のNK細胞の分化に造血細胞が産生するIL-15が必須である --2種類の局在を示すNK細胞の新規分化モデル--. 京都大学プレスリリース. 2023-09-20.Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response

Breastfeeding history and metabolic syndrome in parous women

Objective The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. Methods The present cross-sectional study included 11,118 women, aged 35–69 years. Participants’ longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. Results Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose–response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. Conclusions Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women

Decadal–centennial-scale solar-linked climate variations and millennial-scale internal oscillations during the Early Cretaceous

Understanding climate variability and stability under extremely warm ‘greenhouse’ conditions in the past is essential for future climate predictions. However, information on millennial-scale (and shorter) climate variability during such periods is scarce, owing to a lack of suitable high-resolution, deep-time archives. Here we present a continuous record of decadal- to orbital-scale continental climate variability from annually laminated lacustrine deposits formed during the late Early Cretaceous (123–120 Ma: late Barremian–early Aptian) in southeastern Mongolia. Inter-annual changes in lake algal productivity for a 1091-year interval reveal a pronounced solar influence on decadal- to centennial-scale climatic variations (including the ~ 11-year Schwabe cycle). Decadally-resolved Ca/Ti ratios (proxy for evaporation/precipitation changes) for a ~ 355-kyr long interval further indicate millennial-scale (~ 1000–2000-yr) extreme drought events in inner-continental areas of mid-latitude palaeo-Asia during the Cretaceous. Millennial-scale oscillations in Ca/Ti ratio show distinct amplitude modulation (AM) induced by the precession, obliquity and short eccentricity cycles. Similar millennial-scale AM by Milankovitch cycle band was also previously observed in the abrupt climatic oscillations (known as Dansgaard–Oeschger events) in the ‘intermediate glacial’ state of the late Pleistocene, and in their potential analogues in the Jurassic ‘greenhouse’. Our findings indicate that external solar activity forcing was effective on decadal–centennial timescales, whilst the millennial-scale variations were likely amplified by internal process such as changes in deep-water formation strength, even during the Cretaceous ‘greenhouse’ period