A PTER-dependent pathway of taurine metabolism linked to energy balance.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

Convergent evolutionary patterns of heterostyly across angiosperms support the pollination-precision hypothesis.

Since the insights by Charles Darwin, heterostyly, a floral polymorphism with morphs bearing stigmas and anthers at reciprocal heights, has become a model system for the study of natural selection. Based on his archetypal heterostylous flower, including regular symmetry, few stamens and a tube, Darwin hypothesised that heterostyly evolved to promote outcrossing through efficient pollen transfer between morphs involving different areas of a pollinator's body, thus proposing his seminal pollination-precision hypothesis. Here we update the number of heterostylous and other style-length polymorphic taxa to 247 genera belonging to 34 families, notably expanding known cases by 20%. Using phylogenetic and comparative analyses across the angiosperms, we show numerous independent origins of style-length polymorphism associated with actinomorphic, tubular flowers with a low number of sex organs, stamens fused to the corolla, and pollination by long-tongued insects. These associations provide support for the Darwinian pollination-precision hypothesis as a basis for convergent evolution of heterostyly across angiosperms.

MED15::ATF1-Rearranged Tumor: A Novel Cutaneous Tumor With Melanocytic Differentiation.

We recently described novel dermal tumors with melanocytic differentiation and morphologic and biological similarities to cutaneous clear cell sarcoma, including CRTC1::TRIM11 cutaneous tumor, and clear cell tumors with melanocytic differentiation and either ACTIN::MITF or MITF::CREM. Here, we describe a series of 3 patients presenting with tumors reminiscent of CRTC1::TRIM11 cutaneous tumor, found to demonstrate a novel MED15::ATF1 fusion. All 3 patients were children (5-16 years old). Primary excision of case 1 showed a circumscribed wedge-shaped silhouette with peripheral intercalation into collagen fibers and scattered lymphoid aggregates. All 3 tumors abutted the epidermis; one showed a junctional component. Tumors were highly cellular and comprised of monomorphic, oval-to-round epithelioid cells arranged in vague nests and short fascicles in variably fibrotic stroma. Mitotic rate was high (hotspot 6-12/mm2), without atypical mitoses. Necrosis was focally present in case 3. All cases showed strong, diffuse nuclear staining for SOX10 and MITF (2/2) but showed variable expression for S100 protein (1/3) and other melanocytic markers-Melan-A (focal in 2/3), HMB45 (focal in 1/3), and Pan-Melanoma (patchy in 1/1). Whole-exome RNA sequencing demonstrated a MED15::ATF1 fusion without any other notable alterations. Cases 1 and 2 were completely excised without recurrence (12 months). Case 3 developed a grossly apparent regional lymph node spread shortly after primary biopsy. The patient was treated with wide excision, radiation, cervical lymph node dissection (4/46 with >75% lymph node replacement), and neoadjuvant and adjuvant nivolumab (alive without disease at cycle 11). This series is presented to aid in future diagnosis of this novel dermal tumor with melanocytic differentiation and emphasize the potential for aggressive biologic behavior, which should be considered in patient management planning.

Strategies to reduce ileus after colorectal surgery: A qualitative umbrella review of the collective evidence.

BACKGROUND: Various strategies were proposed to reduce postoperative ileus after colorectal surgery. This umbrella review aimed to provide a comprehensive overview of current evidence on measures to reduce the incidence and severity of postoperative ileus after colorectal surgery. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic search was conducted in PubMed and Scopus to identify systematic reviews that assessed the efficacy of interventions used to prevent postoperative ileus after colorectal surgery. Data on study characteristics, interventions, and outcomes were summarized in a narrative manner. RESULTS: A total of 26 systematic reviews incorporating various strategies like early oral feeding, gum chewing, coffee consumption, medications, and acupuncture were included. Early oral feeding reduced postoperative ileus and accelerated bowel function return. The most assessed intervention was chewing gum, which was associated with a median reduction of postoperative ileus by 45% (range, 11%-59%) and shortening of the time to first flatus and time to defecation by a median of 11.9 and 17.7 hours, respectively. Coffee intake showed inconsistent results, with a median shortening of time to flatus and time to defecation by 1.32 and 14.45 hours, respectively. CONCLUSION: Early oral feeding, chewing gum, and alvimopan were the most commonly assessed and effective strategies for reducing postoperative ileus after colorectal surgery. Medications used to reduce postoperative ileus included alvimopan, intravenous lidocaine, dexamethasone, probiotics, and oral antibiotics. Intravenous dexamethasone and lidocaine and oral probiotics helped hasten bowel function return. Acupuncture positively impacted the recovery of bowel function.

The economy of pollen dispersal in flowering plants.

Mating success of flowering plants depends strongly on the efficiencies of pollen removal from flowers and its subsequent dispersal to conspecific stigmas. We characterized the economy of pollen dispersal in flowering plants by analysing pollen fates and their correlates for 228 species. The mean percentage of pollen removed from flowers (removal efficiency) varied almost twofold according to the type of pollen-dispersal unit, from less than 45% for orchids and milkweeds with solid pollinia, to greater than 80% for species with granular monads or sectile (segmented) pollinia. The mean percentage of removed pollen reaching stigmas (pollen transfer efficiency, PTE) varied from 2.4% for species with separate monads to 27.0% for orchids with solid pollinia. These values tended to be higher in plants with single pollinator species and in those with non-grooming pollinators. Nectar production increased removal efficiency, but did not influence PTE. Among types of pollen-dispersal units, the net percentage of produced pollen that was dispersed to stigmas varied negatively with removal efficiency and positively with PTE, indicating the relative importance of the latter for overall pollen economy. These findings confirm the key importance of floral traits, particularly pollen packaging, for pollen dispersal outcomes and highlight the under-appreciated pollination efficiency of non-grooming pollinators.

A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.

BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies. RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I2 = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I2 = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis. CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform.

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Beyond pollen:ovule ratios: Evolutionary consequences of pollinator dependence and pollination efficiency for pollen and ovule production in angiosperms.

PREMISE: The relative per-flower production of ovules and pollen varies broadly with angiosperm mating systems, with outcrossing types commonly producing more pollen grains per ovule than selfing types. The evolutionary causes of this variation are contentious, especially the relevance of pollination risk. Resolution of this debate may have been hampered by its focus on pollen:ovule (P:O) ratios rather than on the evolution of pollen and ovule numbers per se. METHODS: Using published mean ovule and pollen counts, we analyzed associations with the proportion of removed pollen that reaches stigmas (pollen-transfer efficiency) and differences between pollinator-dependent and autogamous forms within and among species. Analyses involved Bayesian methods that simultaneously considered variation in pollen and ovule numbers and accounted for phylogenetic relatedness. We also assessed the utility of P:O ratios as mating-system proxies and their association with female outcrossing rates. RESULTS: Median pollen number declined consistently with pollen-transfer efficiency among species, whereas median ovule number did not. Similarly, in both intraspecific and interspecific analyses, pollinator-dependent plants produced more pollen than autogamous plants, whereas ovule production did not differ statistically. Distributions of P:O ratios overlapped extensively for self-incompatible and self-compatible species and for different mating-system classes, and P:O ratios correlated weakly with outcrossing rate. CONCLUSIONS: Our findings demonstrate that pollinator dependence and pollination efficiency commonly influence the evolution of pollen number per flower but have more limited effects on ovule number. P:O ratios provide ambiguous, possibly misleading, information about mating systems, especially when compared among clades.

Cytoreductive Surgery and Hyperthermic Peritoneal Chemotherapy in Appendiceal and Colorectal Cancer: Outcomes and Survival.

BACKGROUND: We reviewed outcomes following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal or colorectal neoplasms and evaluated key prognostic indicators for treatment. METHODS: All patients who underwent cytoreductive surgery/HIPEC for appendiceal and colorectal neoplasms were identified from an IRB-approved database. Patient demographics, operative reports, and postoperative outcomes were reviewed. RESULTS: 110 patients [median age 54.5 (18-79) years, 55% male] were included. Primary tumor location was colorectal (58; 52.7%) and appendiceal (52; 47.3%). 28.2%, .9%, and 12.7% had right, left, and sigmoid tumors, respectively; 11.8% had rectal tumors. 12/13 rectal cancer patients underwent preoperative radiotherapy. Mean Peritoneal Cancer Index was 9.6 ± 7.7; complete cytoreduction was achieved in 90.9%. 53.6% developed postoperative complications. Reoperation, perioperative mortality, and 30-day readmission rates were 1.8%, .09%, and 13.6%, respectively. Recurrence at a median of 11.1 months was 48.2%; overall survival at 1 and 2 years was 84% and 56.8%, respectively; disease-free survival was 60.8% and 33.7%, respectively, at a median follow-up of 16.8 (0-86.8) months. Univariate analysis of preoperative chemotherapy, primary malignancy location, primary tumor perforated or obstructive, postoperative bleeding complication, and pathology of adenocarcinoma, mucinous adenocarcinoma and negative lymph nodes were identified as possible predictive factors of survival. Multivariate logistic regression analysis showed that preoperative chemotherapy (P < .001), perforated tumor (P = .003), and postoperative intra-abdominal bleeding (P < .001) were independent prognostic indicators for survival. CONCLUSIONS: Cytoreductive surgery/HIPEC for colorectal and appendiceal neoplasms has low mortality and high completeness of cytoreduction score. Preoperative chemotherapy, primary tumor perforation, and postoperative bleeding are adverse risk factors for survival.

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Utilizing Patient-Derived Organoids in the Management of Colorectal Cancer with Peritoneal Metastases: A Review of Current Literature.

INTRODUCTION: Treatment of colorectal cancer-derived peritoneal carcinomatosis (CRC-PC) is challenging due to cellular heterogeneity that exhibits variable degrees of resistance to systemic as well as intraperitoneal chemotherapy. Therefore, it is not a surprise that the majority of patients undergoing cytoreductive surgery with HIPEC will experience recurrence. Patient-derived tumor organoids (PTOs) may be potentially capable of informing clinical treatment decisions at the level of the individual patient. In this study, we review the current landscape of CRC-PC PTO literature. METHODS: PubMed was queried for peer-reviewed publications studying CRC-PC organoids. Original articles which harnessed organoids as a research platform to study CRC-PC were included for review. Xenograft organoid studies were excluded. RESULTS: A total of 5 articles met inclusion criteria published between 2017 and 2022 and underwent complete analysis. Study topics included optimization of current therapies, identification of novel drug applications, and identification of disease mechanisms. Current therapies studied included systemic chemotherapy, targeted inhibitors, and HIPEC regimens. CONCLUSIONS: Patient-derived tumor organoids are a valuable personalized research tool that can complement real-time clinical settings. Additional research is needed to optimize methodologies of organoid incorporation in patients with colorectal cancer with peritoneal carcinomatosis.

The lady's 'slippery' orchid: functions of the floral trap and aphid mimicry in a hoverfly-pollinated Phragmipedium species in Brazil.

BACKGROUND AND AIMS: Trap flowers are fascinating cases of adaptation, often linked to oviposition-site mimicry systems. Some trap flowers do not imprison pollinators for a pre-determined period, but rather force them to move through a specific path, manipulating their movements in a way that culminates in pollen transfer, often as they leave through a secondary opening. METHODS: We investigated the previously unknown pollination system of the lady's slipper orchid Phragmipedium vittatum and assessed the function of micro-morphological traits of its trap flowers. KEY RESULTS: Our observations revealed that P. vittatum is pollinated by females of two hoverfly species (Syrphidae). Eggs laid by flies on or near raised black spots on the flowers indicate that the orchid mimics aphids which serve as food for their aphidophagous larvae. Dark, elevated aphid-like spots appear to attract the attention of hoverflies to a slipping zone. This region has downward projecting papillate cells and mucilage secretion that promote slipperiness, causing potential pollinators to fall into the labellum. They then follow a specific upward route towards inner aphid-like spots by holding onto upward oriented hairs that aid their grip. As hoverflies are funnelled by the lateral constriction of the labellum, they pass the stigma, depositing pollen they may be carrying. Later, they squeeze under one of the articulated anthers which places pollen smears onto their upper thorax. Then, they depart through one of the narrow lateral holes by holding onto hairs projecting from the petals. CONCLUSIONS: This study confirms the system of aphid mimicry in Phragmipedium and highlights the sophisticated micro-morphological traits used by trap flowers in pollinator attraction, trapping, guidance and release, thus promoting precise pollen transfer.

Understanding Variation in Adoption of Video Telehealth and Implications for Health Care Systems.

Background: Telehealth has rapidly expanded since COVID-19. Veterans Health Administration (VHA), the largest integrated health care system in the United States, was well-positioned to incorporate telehealth across specialties due to existing policies and infrastructure. Objectives: The objective of this study is to investigate predictors of occupational therapy (OT) practitioners' adoption of video telehealth. Methods: This study presents data from a convenience sample of VHA occupational therapy (OT) practitioners administered pre-pandemic, in fall 2019. Survey development was guided by the Promoting Action on Research Implementation in Health Services framework, and gathered clinician attitudes, experiences, and perspectives about video telehealth to deliver OT services. Items included telehealth usage, perceived effectiveness of specific OT interventions, and perceptions about evidence. Our outcome variable denoted practitioners' level of adoption of video telehealth: telehealth users (adopters), non-users who want to use telehealth (potential adopters and reference group), and non-users who do not want to use telehealth (non-adopters). In multiple multinomial logistic regressions, we tested whether level of adoption was associated with years of VHA work experience and perceived strength of evidence. Results: Of approximately 1455 eligible practitioners, 305 VHA occupational therapy practitioners participated in the survey (21% response rate). One hundred and twenty-five (41%) reported using video telehealth, whereas 180 (59%) reported not using video telehealth. Among non-users, 107 (59%) indicated willingness to adopt telehealth whereas 73 (41%) were not willing. More VHA work experience predicted higher odds of being an adopter than a potential adopter; perceptions of stronger evidence regarding video telehealth predicted higher odds of being a potential adopter than a non-adopter. Conclusion: Clinician beliefs and years of experience exerted an influence on clinicians' use or willingness to use video telehealth. Efforts to enhance adoption of video telehealth should address clinicians' beliefs regarding the innovative nature of and organizational resources necessary to foster utilization.

Why honeybees are poor pollinators of a mass-flowering plant: Experimental support for the low pollen quality hypothesis.

PREMISE: Honeybees dominate the flower-visitor assemblages of many plant species, yet their efficiency in terms of the quality of pollen delivered to stigmas is largely unknown. We investigated why honeybees are poor pollinators of Aloe ferox, a self-incompatible succulent treelet with large numbers of flowers. Honeybees are very frequent visitors to flowers of this species, yet contribute very little to seed production. METHODS: We assessed pollen loads on honeybees, studied their visitation behavior, selectively excluded birds from plants to determine direct effects of bees on pollen deposition, seed set, and ovule abortion, and used a novel "split-pollinator" method to test whether honeybees deposit mainly low-quality self pollen. For the latter, we captured honeybees, and with their existing pollen loads, used them to either pollinate virgin flowers on the plant on which they were caught or to pollinate virgin flowers on different plants. RESULTS: Honeybees cumulatively deposit as much pollen on stigmas as do birds, but our experiments showed that the pollen deposited by honeybees is mostly low-quality self pollen that leads to substantial ovule discounting and depressed seed set. CONCLUSIONS: Lack of movement among A. ferox plants during individual honeybee foraging bouts is the most likely explanation for their deposition of low-quality self pollen on stigmas. The "split-pollinator" method is a simple and cost-effective technique to test the quality of pollination.

At the beginnings of the funerary Megalithism in Iberia at Campo de Hockey necropolis.

The excavations undertaken at the Campo de Hockey site in 2008 led to the identification of a major Neolithic necropolis in the former Island of San Fernando (Bay of Cádiz). This work presents the results of the latest studies, which indicate that the site stands as one of the oldest megalithic necropolises in the Iberian Peninsula. The main aim of this work is to present with precision the chronology of this necropolis through a Bayesian statistical model that confirms that the necropolis was in use from c. 4300 to 3800 cal BC. The presence of prestige grave goods in the earliest and most monumental graves suggest that the Megalithism phenomenon emerged in relation to maritime routes linked to the distribution of exotic products. We also aim to examine funerary practices in these early megalithic communities, and especially their way of life and the social reproduction system. As such, in addition to the chronological information and the Bayesian statistics, we provide the results of a comprehensive interdisciplinary study, including anthropological, archaeometric and genetic data.

Community based participatory research approaches to combat oral health inequities among American Indian and Alaska Native populations.

American Indian and Alaska Native (AI/AN) communities have experienced a history of systemic racism and still face significant oral health disparities. These disparities extend to the youngest community members in the form of early childhood caries (ECC). Although behavior and biology contribute to ECC, the conditions where people live, grow, and work, and the systems and political and economic forces that shape individual health outcomes, are thought to greatly impact ECC among AI/AN populations. To address ECC in AI/AN communities, we used a community based participatory approach that incorporated social determinants of health. We found that implementing culturally-tailored, culturally-centered, and AI/AN-created materials for ECC interventions is viewed favorably by community members and tribal leaders. Because of the complexity of ECC in AI/AN communities we adopted a bundled approach of best practices to reduce ECC including: (1) incorporating locally, contextually, and culturally relevant strategies to present recommended ECC prevention approaches; (2) employing AI/AN community members as educators; (3) utilizing motivational interviewing with expectant mothers; and (4) providing fluoride varnish. Our work underscores the importance of developing trusting partnerships with each other and with our communities, drawing upon the insights of community advisory board members, and eliciting formative assessment data from tribal members to gain a more holistic understanding of our participants' lived experience to design relevant intervention materials. Incorporating local knowledge and situating Western oral health prevention approaches within culturally aligned frameworks can enhance partnerships and create sustainable materials for community work.

Deciphering Redox State for a Metal-Rich World.

The Psyche mission's Oxidation-Reduction Working Group is focused on understanding, determining, and applying the redox state of (16) Psyche to understand the origin of a metal-rich world. The oxidation-reduction state of an asteroid, along with its temperature, parent body size, and composition, is a key parameter in determining the history of an asteroid. Determining the redox state from spacecraft data is most easily done by examining potential metal-oxide buffer pairs. The occurrence of Ni, Fe, C, Cr, P and Si, in that order, in the metal or sulfide phase of an asteroidal body indicates increasingly reduced conditions. Key observations by the Imager and Gamma-Ray and Neutron Spectrometer (GRNS) of Psyche can bracket the redox state using metal-oxide buffers. The presence of Fe,Ni metal can be confirmed by the ratios of Fe/O or Fe/Si and the concentration of Ni variability in metal across the asteroid can be determined by GRNS. The FeO concentration of silicates is complementary to the Ni concentration of metal and can be constrained using filters on the Imager. The presence of FeO in silicates from ground-based observations is one of the few measurements we already have of redox state, although available data permit a wide range of silicate compositions and mineralogies. The presence of C, P or Si concentrated in the metallic, Fe-rich portion of the asteroid, as measured by GRNS, or Ca-sulfide, determined by imaging, would indicate increasingly reducing conditions. Linkage to known types of meteorites, whether metal-rich chondrites, stony-irons or irons, expands the mineralogical, chemical and isotopic data not available from remote observations alone. Redox also controls both silicate and metal mineralogy, influencing differentiation, solidification, and subsolidus cooling, including the relative abundance of sulfur in the core and possible magnetic signatures. The redox state of Psyche, if a fully-differentiated metallic core, might constrain the location and timing of both the formation of Psyche and any oxidation it might have experienced.