Embryology of the fat-tailed dunnart (Sminthopsis crassicaudata): A marsupial model for comparative mammalian developmental and evolutionary biology.

BACKGROUND: Marsupials are a diverse and unique group of mammals, but remain underutilized in developmental biology studies, hindering our understanding of mammalian diversity. This study focuses on establishing the fat-tailed dunnart (Sminthopsis crassicaudata) as an emerging laboratory model, providing reproductive monitoring methods and a detailed atlas of its embryonic development. RESULTS: We monitored the reproductive cycles of female dunnarts and established methods to confirm pregnancy and generate timed embryos. With this, we characterized dunnart embryo development from cleavage to birth, and provided detailed descriptions of its organogenesis and heterochronic growth patterns. Drawing stage-matched comparisons with other species, we highlight the dunnarts accelerated craniofacial and limb development, characteristic of marsupials. CONCLUSIONS: The fat-tailed dunnart is an exceptional marsupial model for developmental studies, where our detailed practices for reproductive monitoring and embryo collection enhance its accessibility in other laboratories. The accelerated developmental patterns observed in the Dunnart provide a valuable system for investigating molecular mechanisms underlying heterochrony. This study not only contributes to our understanding of marsupial development but also equips the scientific community with new resources for addressing biodiversity challenges and developing effective conservation strategies in marsupials.

Recent advances in reproductive research in Australia and New Zealand: highlights from the Annual Meeting of the Society for Reproductive Biology, 2022.

In 2022, the Society for Reproductive Biology came together in Christchurch New Zealand (NZ), for its first face-to-face meeting since the global COVID-19 pandemic. The meeting showcased recent advancements in reproductive research across a diverse range of themes relevant to human health and fertility, exotic species conservation, and agricultural breeding practices. Here, we highlight the key advances presented across the main themes of the meeting, including advances in addressing opportunities and challenges in reproductive health related to First Nations people in Australia and NZ; increasing conservation success of exotic species, including ethical management of invasive species; improvements in our understanding of developmental biology, specifically seminal fluid signalling, ovarian development and effects of environmental impacts such as endocrine-disrupting chemicals; and leveraging scientific breakthroughs in reproductive engineering to drive solutions for fertility, including in assisted reproductive technologies in humans and agricultural industries, and for regenerative medicine.

A chromosome-scale assembly for 'd'Anjou' pear.

Cultivated pear consists of several Pyrus species with Pyrus communis (European pear) representing a large fraction of worldwide production. As a relatively recently domesticated crop and perennial tree, pear can benefit from genome-assisted breeding. Additionally, comparative genomics within Rosaceae promises greater understanding of evolution within this economically important family. Here, we generate a fully phased chromosome-scale genome assembly of P. communis 'd'Anjou.' Using PacBio HiFi and Dovetail Omni-C reads, the genome is resolved into the expected 17 chromosomes, with each haplotype totaling nearly 540 Megabases and a contig N50 of nearly 14 Mb. Both haplotypes are highly syntenic to each other and to the Malus domestica 'Honeycrisp' apple genome. Nearly 45,000 genes were annotated in each haplotype, over 90% of which have direct RNA-seq expression evidence. We detect signatures of the known whole-genome duplication shared between apple and pear, and we estimate 57% of d'Anjou genes are retained in duplicate derived from this event. This genome highlights the value of generating phased diploid assemblies for recovering the full allelic complement in highly heterozygous crop species.

Detrimental actions of obesity-associated advanced glycation end-products on endometrial epithelial cell proliferation are alleviated by antioxidants.

RESEARCH QUESTION: Advanced glycation end-products (AGE) are elevated in the uterine environment of obese infertile women. Can the detrimental effects of AGE on endometrial epithelial cells be mitigated with therapeutics, and recapitulated in a more physiologically relevant primary model (organoids)? DESIGN: Human endometrial epithelial cells (ECC-1) were exposed to AGE at concentrations physiologically representative of uterine fluid in lean or obese individuals, and three potential therapeutics: 25 nmol/l receptor for AGE (RAGE) antagonist FPS-ZM1, 100 µmol/l metformin, or a combination of antioxidants (10 µmol/l N-acetyl-l-cysteine, 10 µmol/l N-acetyl-l-carnitine and 5 µmol/l α-lipoic acid). Real-time cell analysis (xCELLigence, ACEA Biosciences) determined the rate of adhesion and proliferation. The proliferation of organoid-derived cells and secretion of cytokines from organoids was characterized in the presence of AGE (n = 5). The uterine fluid of women undergoing assisted reproduction was profiled for AGE-associated inflammatory markers (n = 77). RESULTS: ECC-1 proliferation was reduced by AGE from obese versus lean conditions and vehicle control (P = 0.04 and P < 0.001, respectively), and restored to a proliferation corresponding to lean conditions by antioxidants. AGE influenced organoid derived primary endometrial epithelial cell proliferation in a donor-dependent manner. AGE increased the organoid secretion of the proinflammatory cytokine CXCL16 (P = 0.006). Clinically, CXCL16 correlated positively to maternal body mass index (R = 0.264, P = 0.021) and intrauterine glucose concentration (R = 0.736, P < 0.0001). CONCLUSIONS: Physiologically relevant concentrations of AGE alter endometrial epithelial cell function. Antioxidants restore the rate of proliferation of AGE-treated endometrial epithelial (ECC-1) cells. Primary endometrial epithelial cells, cultured as organoids, demonstrate altered proliferation and CXCL16 secretion in the presence of AGE equimolar with the uterine fluid from obese individuals.

Improving Family-Centered Care for Infants in Neonatal Intensive Care Units: Recommendations From Frontline Healthcare Professionals.

BACKGROUND: Family-centered care is a philosophy and healthcare delivery model adopted by many neonatal intensive care units (NICUs) worldwide, yet practice varies widely. PURPOSE: The aim of this study was to synthesize recommendations from frontline NICU healthcare professionals regarding family-centered care. METHODS: Data were obtained from the baseline phase of a multicenter quasi-experimental study comparing usual family-centered NICU care (baseline) with mobile-enhanced family integrated care (intervention). Members of the NICU clinical care team completed a family-centered care survey and provided free-text comments regarding practice of family-centered care in their NICU and recommendations for improvement. The comments were analyzed using a directed content analysis approach by a research team that included NICU nurses and parents. RESULTS: Of the 382 NICU healthcare providers from 6 NICUs who completed the survey, 68 (18%) provided 89 free-text comments/recommendations about family-centered care. Almost all comments were provided by nurses (91%). Six main themes were identified: language translation; communication between staff and families; staffing and workflow; team culture and leadership; education; and NICU environment. The need for greater resources for staffing, education, and environmental supports was prominent among the comments, as was team culture and staff-parent communications. IMPLICATIONS FOR PRACTICE: The NICU healthcare professionals identified a range of issues that support or impede delivery of family-centered care and provided actionable recommendations for improvement. IMPLICATIONS FOR RESEARCH: Future research should include economic analyses that will enable determination of the return on investment so that NICUs can better justify the human and capital resources needed to implement high-quality family-centered care.

A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation.

RESEARCH QUESTION: Is the blastocyst's idiosyncratic metabolic production of lactate, and creation of a specialized microenvironment at the implatation site, an important mediator of maternal-fetal signalling to promote endometrial receptivity and implantation? DESIGN: Hormonally primed ECC-1 and Ishikawa cells were used to assess functional changes to the endometrial epithelium after exposure to lactic acid (LA), LA with neutralized pH (nLA) or acidic pH (pHL). Tight junction integrity (transepithelial resistance [TER]), cellular proliferation or changes to gene expression by RT-PCR were analysed. The effect of LA on Endometrial stromal cells decidualization and migratory capacity, and HUVEC endothelial tube formation and angiogenesis, were also assessed. RESULTS: Treatment of ECC-1 cells with 2.5 mM (P = 0.0037), 5 mM (P = 0.0044), 7.5 mM and 10 mM (P = 0.003) (P = 0.0021) LA significantly decreased the rate of cellular proliferation while TER was decreased with exposure to 2.5 mM LA (P = 0.024), 5 mM LA (P = 0.021) and 7.5 mM LA (P = 0.033). Exposure to nLA or pHL had no effect on proliferation or TER. Upregulation of GLUT4 (P = 0.002), GPR81 (P = 0.048), VEGF, SNAI1 (both P < 0.001) and RELA (P = 0.023) mRNA expression was observed after exposure of Ishikawa cells to combined LA plus pHL. Lactic acid increased the migratory capacity of decidualized stromal cells (P = 0.047) without changing the extent of decidualization. HUVEC tube formation was significantly increased by 5 mM LA exposure (P = 0.009). CONCLUSIONS: The identification of LA as an important mediator in the maternal-fetal dialogue underpinning implantation is supported. Further examination of the role of LA within the infertile or compromised endometrium could improve natural and assisted pregnancy success and needs further investigation.

Cyclical endometrial repair and regeneration.

Uniquely among adult tissues, the human endometrium undergoes cyclical shedding, scar-free repair and regeneration during a woman's reproductive life. Therefore, it presents an outstanding model for study of such processes. This Review examines what is known of endometrial repair and regeneration following menstruation and parturition, including comparisons with wound repair and the influence of menstrual fluid components. We also discuss the contribution of endometrial stem/progenitor cells to endometrial regeneration, including the importance of the stem cell niche and stem cell-derived extracellular vesicles. Finally, we comment on the value of endometrial epithelial organoids to extend our understanding of endometrial development and regeneration, as well as therapeutic applications.

A Multisite Survey of NICU Healthcare Professionals' Perceptions About Family-Centered Care.

BACKGROUND: Family-centered care contributes to improved outcomes for preterm and ill infants. Little is known about the perceptions of neonatal intensive care unit (NICU) healthcare professionals regarding the degree to which their NICU practices or values family-centered care. PURPOSE: The aims of this study were to describe attitudes and beliefs of NICU healthcare professionals about family-centered care and to explore professional characteristics that might influence those views. METHODS: Data were derived from the baseline phase of a multicenter quasi-experimental study comparing usual family-centered NICU care with mobile-enhanced family-integrated care. Neonatal intensive care unit healthcare professionals completed the Family-Centered Care Questionnaire-Revised (FCCQ-R), a 45-item measure of 9 core dimensions of Current Practice and Necessary Practice for family-centered care. RESULTS: A total of 382 (43%) NICU healthcare professionals from 6 NICUs completed 1 or more of the FCCQ-R subscales, 83% were registered nurses. Total and subscale scores on the Necessary Practice scale were consistently higher than those on the Current Practice scale for all dimensions of family-centered care (mean: 4.40 [0.46] vs 3.61 [0.53], P < .001). Only years of hospital experience and NICU site were significantly associated with Current Practice and Necessary Practice total scores. IMPLICATIONS FOR PRACTICE: Ongoing assessment of the perceptions of NICU healthcare professionals regarding their current practice and beliefs about what is necessary for the delivery of high-quality family-centered care can inform NICU education, quality improvement, and maintenance of family-centered care during the COVID-19 pandemic. IMPLICATIONS FOR RESEARCH: Further research is needed to identify additional factors that predict family-centered care perceptions and behaviors.

Advanced glycation end products present in the obese uterine environment compromise preimplantation embryo development.

RESEARCH QUESTION: Proinflammatory advanced glycation end products (AGE), highly elevated within the uterine cavity of obese women, compromise endometrial function. Do AGE also impact preimplantation embryo development and function? DESIGN: Mouse embryos were cultured in AGE equimolar to uterine fluid concentrations in lean (1-2 µmol/l) or obese (4-8 µmol/l) women. Differential nuclear staining identified cell allocation to inner cell mass (ICM) and trophectoderm (TE) (day 4 and 5 of culture). Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay (day 5). Day 4 embryos were placed on bovine serum albumin/fibronectin-coated plates and embryo outgrowth assessed 93 h later as a marker of implantation potential. AGE effects on cell lineage allocation were reassessed following pharmacological interventions: either 12.5 nmol/l AGE receptor (RAGE) antagonist; 0.1 nmol/l metformin; or combination of 10 µmol/l acetyl-l-carnitine, 10 µmol/l N-acetyl-l-cysteine, and 5 µmol/l alpha-lipoic acid. RESULTS: 8 µmol/l AGE reduced: hatching rates (day 5, P < 0.01); total cell number (days 4, 5, P < 0.01); TE cell number (day 5, P < 0.01), and embryo outgrowth (P < 0.01). RAGE antagonism improved day 5 TE cell number. CONCLUSIONS: AGE equimolar with the obese uterine environment detrimentally impact preimplantation embryo development. In natural cycles, prolonged exposure to AGE may developmentally compromise embryos, whereas following assisted reproductive technology cycles, placement of a high-quality embryo into an adverse 'high AGE' environment may impede implantation success. The modest impact of short-term RAGE antagonism on improving embryo outcomes indicates preconception AGE reduction via pharmacological or dietary intervention may improve reproductive outcomes for overweight/obese women.

Endometrial inflammasome activation accompanies menstruation and may have implications for systemic inflammatory events of the menstrual cycle.

STUDY QUESTION: Does NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome activation within decidualized endometrial stromal cells accompany menstruation and is this reflected systemically? SUMMARY ANSWER: Components of the NLRP3 inflammasome immunolocalize to decidualized endometrial stromal cells immediately prior to menstruation, and are activated in an in vitro model of menstruation, as evidenced by downstream interleukin (IL)-1beta and IL-18 release, this being reflected systemically in vivo. WHAT IS KNOWN ALREADY: Menstruation is a highly inflammatory event associated with activation of NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), local release of chemokines and cytokines and inflammatory leukocyte influx. Systemically, chemokines and cytokines fluctuate across the menstrual cycle. STUDY DESIGN, SIZE, DURATION: This study examined the NLRP3 inflammasome and activation of downstream IL-1beta and IL-18 in endometrial tissues from women of known fertility (≥1 previous parous pregnancy) across the menstrual cycle (n ≥ 8 per cycle phase), serum from women during the proliferative, secretory and menstrual phases (≥9 per cycle phase) of the cycle and menstrual fluid collected on Day 2 of menses (n = 18). Endometrial stromal cells isolated from endometrial tissue biopsies (n = 10 in total) were used for an in vitro model of pre-menstrual hormone withdrawal. PARTICIPANTS/MATERIALS, SETTING, METHODS: Expression and localization of components of the NLRP3 inflammasome (NLRP3 & apoptosis-associated speck-caspase recruit domain [ASC]) in endometrial tissues was performed by immunohistochemistry. Unbiased digital quantification of immunohistochemical staining allowed determination of different patterns of expression across the menstrual cycle. Serum from women across the menstrual cycle was examined for IL-1beta and IL-18 concentrations by ELISA. An in vitro model of hormone withdrawal from estrogen/progestin decidualized endometrial stromal cells was used to more carefully examine activation of the NLRP3 inflammasome. Endometrial stromal cells isolated from endometrial tissue biopsies (n = 10) were treated with estrogen/medroxyprogesterone acetate for 12 days to induce decidualization (assessed by release of prolactin) followed by withdrawal of steroid hormone support. Activation of NLRP3, & ASC in these cells was examined on Days 0-3 after hormone withdrawal by Western immunoblotting. Release of IL-1beta and IL-18 examined during decidualization and across the same time course of hormone withdrawal by ELISA. Specific involvement of NLRP3 inflammasome activation in IL-1beta and IL-18 release after hormone withdrawal was investigated via application of the NLRP3 inflammasome inhibitor MCC950 at the time of hormone withdrawal. MAIN RESULTS AND THE ROLE OF CHANCE: Critical components of the NLRP3 inflammasome (NLRP3, ASC) were increased in menstrual phase endometrial tissues versus early secretory phase tissues (P < 0.05, n/s, respectively). NLRP3 and ASC were also elevated in the proliferative versus secretory phase of the cycle (P < 0.01, n/s, respectively) with ASC also significantly increased in the late-secretory versus early-secretory phase (P < 0.05). The pattern of activation was reflected in systemic levels of the inflammasome mediators, with IL-1beta and IL-18 elevated in peripheral blood serum during menstruation (Day 2 of menses) versus secretory phase (P = 0.026, P = 0.0042, respectively) and significantly elevated in menstrual fluid (Day 2 of menses) versus systemic levels across all cycle phases, suggesting that local inflammasome activation within the endometrium during menses is reflected by systemic inflammation. NLRP3 and ASC localized to decidualized cells adjacent to the spiral arterioles in the late secretory phase of the menstrual cycle, where the menstrual cascade is thought to be initiated, and to endometrial leukocytes during the menstrual phase. NLRP3 also localized to glandular epithelial cells during the late-secretory/menstrual phases. Localization of both NLRP3 and ASC switched from predominant epithelial localization during the early-secretory phase to stromal localization during the late-secretory/menstrual phase. Using an in vitro model of hormone withdrawal from decidualized human endometrial stromal cells, we demonstrated progressive activation of NLRP3 and ASC after hormone withdrawal increasing from Day 0 of withdrawal/Day 12 of decidualization to Day 3 of withdrawal. Downstream release of IL-1beta and IL-18 from decidualized stromal cells after hormone withdrawal followed the same pattern with the role of NLRP3 inflammasome activation confirmed via the inhibition of IL-1beta and IL-18 release upon application of MCC950. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study uses descriptive and semi-quantitative measures of NLRP3 inflammasome activation within endometrial tissues. Further, the in vitro model of pre-menstrual hormone withdrawal may not accurately recapitulate the in vivo environment as only one cell type is present and medroxyprogesterone acetate replaced natural progesterone due to its longer stability. WIDER IMPLICATIONS OF THE FINDINGS: We provide novel evidence that the NLRP3 inflammasome is activated within decidualized endometrial stromal cells immediately prior to menses and that local activation of the inflammasome within the endometrium appears to be reflected systemically in by activation of downstream IL-1beta and IL-18. Given the prevalence of menstrual disorders associated with inflammation including dysmenorrhoea and aspects of pre-menstrual syndrome, the inflammasome could be a novel target for ameliorating such burdens. STUDY FUNDING/COMPETING INTEREST(S): The authors have no competing interests. J.E. was supported by a Fielding Foundation fellowship, NHMRC project grants (#1139489 and #1141946) and The Hudson Institute of Medical Research. L.A.S. was supported by The Hudson Institute of Medical Research and J.H. by an Australian Government Research Training Program Scholarship. We acknowledge the Victorian Government's Operating Infrastructure funding to the Hudson Institute. TRIAL REGISTRATION NUMBER: N/A.

Proteomic Insights into Endometrial Receptivity and Embryo-Endometrial Epithelium Interaction for Implantation Reveal Critical Determinants of Fertility.

In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo-endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the "final frontier" in infertility. A human coculture model is utilized utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre-implantation human embryos, and primary human endometrial epithelial cells, to functionally identify "fertile" versus "infertile" endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity ("epithelial receptome") and trophectoderm adhesion ("adhesome"). As validation, key "epithelial receptome" proteins (MAGT-1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid-secretory) endometrium obtained from fertile, normally cycling women but is largely absent from non-receptive (proliferative) phase tissues. Factors involved in embryo-epithelium interaction in successive temporal stages of endometrial receptivity and implantation are demonstrated and potential targets for improving fertility are provided, enhancing potential to become pregnant either naturally or in a clinical setting.

New approaches to aquatic and terrestrial animal surveillance: The potential for people and technology to transform epidemiology.

Epidemiology provides insights about causes of diseases and how to control them, and is powered by surveillance information. Animal health surveillance systems typically have been designed to meet high-level government informational needs, and any incentives for those who generate data (such as animal owners and animal health workers) to report surveillance information are sometimes outweighed by the negative consequences of reporting; underreporting is a serious constraint. This problem can persist even when modern advances in information and communications technology (ICT) are incorporated into the structure and operation of surveillance systems, although some problems typical of paper-based systems (including timeliness of reporting and response, accuracy of data entry, and level of detail recorded) are reduced. On occasions, however, additional problems including sustainability arise. We describe two examples of a philosophical approach and ICT platform for the development of powerful and sustainable health information systems that are people-centred and do not exhibit these typical problems. iSIKHNAS is Indonesia's integrated animal health information system, and PIISAC is a sustainable secure research platform based on full production data from participating commercial Chilean aquaculture companies. Epidemiologists working with these systems are faced with interesting new challenges, including the need to develop skills in extracting appropriate surveillance outcomes from large volumes of continually-streaming data.

Differential growth of bowel commensal Bacteroides species on plant xylans of differing structural complexity.

Alterations to the composition of the bowel microbiota (dysbioses) are associated with particular diseases and conditions of humans. There is a need to discover new, indigestible polysaccharides which are selective growth substrates for commensal bowel bacteria. These substrates (prebiotics) could be added to food in intervention studies to correct bowel dysbiosis. A collection of commensal bacteria was screened for growth in culture using a highly-branched xylan produced by New Zealand flax. Two, Bacteroides ovatus ATCC 8483 and Bacteroides xylanisolvens DSM 18836 grew well on this substrate. The utilisation of the xylan was studied chromatographically and by constituent sugar analysis. The two closely related species utilised the xylan in different ways, and differently from their use of wheat arabinoxylan. The growth of Bacteroides species on other plant xylans having differing chemical structures was also investigated. Novel xylans expand the choice of potential prebiotics that could be used to correct bowel dysbioses.

A comparative study of the morphology of mammalian chordae tendineae of the mitral and tricuspid valves.

It is assumed that the human heart is almost identical to domestic mammalian species, but with limited literature to support this. One such area that has been underinvestigated is that of the subvalvular apparatus level. The authors set out to examine the morphology of the subvalvular apparatus of the mammalian atrioventricular valves through gross dissection and microscopic analysis in a small-scale pilot study. The authors examined the chordae tendineae of the mitral and tricuspid valves in sheep, pig and bovine hearts, comparing the numbers of each of these structures within and between species. It was found that the number of chordae was up to twice as many for the tricuspid valve compared with the mitral valve. The counts for the chordae on the three valve leaflets of the tricuspid valve, as well as the two mitral valve leaflets, were almost identical between species. However, the chordae attaching onto the posterior papillary muscle were almost double compared with the septal and anterior papillary muscles. Histological analysis demonstrated an abrupt transitional zone. In conclusion, the authors have shown that there is no gross morphological difference between, or within, these species at the subvalvular apparatus level.

How microRNAs influence both hereditary and inflammatory-mediated colon cancers.

MicroRNAs have emerged as important post-translational regulators of gene expression and are involved in several physiological and pathological states including the pathogenesis of human colon cancers. In regards to tumor development, microRNAs can act as oncogenes or tumor suppressors. Two hereditary predispositions (i.e., Lynch syndrome and familial adenomatous polyposis) contribute to the development of colon cancer. In addition, individuals who suffer from inflammatory bowel diseases such as Crohn's disease or ulcerative colitis have a higher risk of developing colon cancer. Here, we discuss the occurrence of the deregulated expression of microRNAs in colon cancer that arise as a result of hereditary predisposition and inflammatory bowel disease.

S100P/RAGE signaling regulates microRNA-155 expression via AP-1 activation in colon cancer.

Accumulating evidence indicates that elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite these observations, little is known about the downstream targets of S100P/RAGE signaling. In the present study, we demonstrated for the first time that activation of RAGE by S100P regulates oncogenic microRNA-155 (miR-155) expression through Activator Protein-1 (AP-1) stimulation in colon cancer cells. Ectopic S100P up-regulated miR-155 levels in human colon cancer cells. Conversely, knockdown of S100P resulted in a decrease in miR-155 levels. Exogenous S100P induced miR-155 expression, but blockage of the RAGE with anti-RAGE antibody suppressed the induction of miR-155 by exogenous S100P. Attenuation of AP-1 activation through pharmacological inhibition of MEK activation or genetic inhibition of c-Jun activation using dominant negative c-Jun (TAM67) suppressed miR-155 induction by exogenous S100P. Also, S100P treatment stimulated the enrichment of c-Fos, an AP-1 family member, at the miR-155 host gene promoter site. Finally, a functional study demonstrated that miR-155 knockdown decreases colon cancer cell growth, motility, and invasion. Altogether, these data demonstrate that the expression of miR-155 is regulated by S100P and is dependent on RAGE activation and stimulation of AP-1.

Leftward lighting in advertisements increases advertisement ratings and purchase intention.

It has been reliably shown that light is assumed to come from above. There is also some suggestion that light from the left might be preferred. Leftward lighting biases have been observed across various mediums such as paintings, portraits, photographs, and advertisements. As advertisements are used to persuade the public to purchase products, it was of interest to better understand whether leftward lighting would influence future intention to purchase. Participants gave preference ratings for pairs of advertisements with opposing lighting directions. Attitude towards the advertisement and the brand as well as future purchase intention was then rated. Overall, participants indicated that they preferred advertisements with leftward lighting and were more likely to purchase these products in the future than when the same products were lit from the right. Findings are consistent with previously observed leftward lighting biases and suggest that advertisements with a leftward lighting bias might be more effective.

Birth and death rate estimates of cats and dogs in U.S. households and related factors.

Studies report variable factors associated with dog and cat surpluses in the United States. Estimates of cat and dog birth and death rates help understand the problem. This study collected data through a commercial survey company, distributing questionnaires to 7,399 cat- and dog-owning households (HHs) in 1996. The study used an unequal probability sampling plan and reported estimates of means and variances as weighted averages. The study used estimates of HHs and companion animals for national projections. More than 9 million owned cats and dogs died during 1996-yielding crude death rates of 8.3 cat deaths/100 cats in HHs and 7.9 dog deaths/100 dogs in HHs. The study reported twice as many kitten as puppy litters, with an average litter size of 5.73 and 7.57, respectively. The study reported data on planned versus unplanned litters, reasons caregivers did not spay females, disposition of litters, and sources of animals added to HHs. These first national estimates indicate the magnitude of, and reasons for, animals leaving HHs. The crude birth rate was estimated to be 11.2 kittens/100 cats in HHs and 11.4 puppies/100 dogs in HHs.