RFX6 regulates human intestinal patterning and function upstream of PDX1.

The gastrointestinal (GI) tract is complex and consists of multiple organs with unique functions. Rare gene variants can cause congenital malformations of the human GI tract, although the molecular basis of these has been poorly studied. We identified a patient with compound-heterozygous variants in RFX6 presenting with duodenal malrotation and atresia, implicating RFX6 in development of the proximal intestine. To identify how mutations in RFX6 impact intestinal patterning and function, we derived induced pluripotent stem cells from this patient to generate human intestinal organoids (HIOs). We identified that the duodenal HIOs and human tissues had mixed regional identity, with gastric and ileal features. CRISPR-mediated correction of RFX6 restored duodenal identity. We then used gain- and loss-of-function and transcriptomic approaches in HIOs and Xenopus embryos to identify that PDX1 is a downstream transcriptional target of RFX6 required for duodenal development. However, RFX6 had additional PDX1-independent transcriptional targets involving multiple components of signaling pathways that are required for establishing early regional identity in the GI tract. In summary, we have identified RFX6 as a key regulator in intestinal patterning that acts by regulating transcriptional and signaling pathways.

Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

Environmental predictors of Escherichia coli concentration at marine beaches in Vancouver, Canada: a Bayesian mixed-effects modelling analysis.

Understanding historical environmental determinants associated with the risk of elevated marine water contamination could enhance monitoring marine beaches in a Canadian setting, which can also inform predictive marine water quality models and ongoing climate change preparedness efforts. This study aimed to assess the combination of environmental factors that best predicts Escherichia coli (E. coli) concentration at public beaches in Metro Vancouver, British Columbia, by combining the region's microbial water quality data and publicly available environmental data from 2013 to 2021. We developed a Bayesian log-normal mixed-effects regression model to evaluate predictors of geometric E. coli concentrations at 15 beaches in the Metro Vancouver Region. We identified that higher levels of geometric mean E. coli levels were predicted by higher previous sample day E. coli concentrations, higher rainfall in the preceding 48 h, and higher 24-h average air temperature at the median or higher levels of the 24-h mean ultraviolet (UV) index. In contrast, higher levels of mean salinity were predicted to result in lower levels of E. coli. Finally, we determined that the average effects of the predictors varied highly by beach. Our findings could form the basis for building real-time predictive marine water quality models to enable more timely beach management decision-making.

Nuclear structure opportunities with GeV radioactive beams at FAIR.

The Facility for Antiproton and Ion Research (FAIR) is in its final construction stage next to the campus of the Gesellschaft für Schwerionenforschung Helmholtzzentrum for heavy-ion research in Darmstadt, Germany. Once it starts its operation, it will be the main nuclear physics research facility in many basic sciences and their applications in Europe for the coming decades. Owing to the ability of the new fragment separator, Super-FRagment Separator, to produce high-intensity radioactive ion beams in the energy range up to about 2 GeV/nucleon, these can be used in various nuclear reactions. This opens a unique opportunity for various nuclear structure studies across a range of fields and scales: from low-energy physics via the investigation of multi-neutron systems and halos to high-density nuclear matter and the equation of state, following heavy-ion collisions, fission and study of short-range correlations in nuclei and hypernuclei. The newly developed reactions with relativistic radioactive beams (R3B) set up at FAIR would be the most suitable and versatile for such studies. An overview of highlighted physics cases foreseen at R3B is given, along with possible future opportunities, at FAIR. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.

Modifying the electronic and magnetic properties of the scandium nitride semiconductor monolayer via vacancies and doping.

In this work, the effects of vacancies and doping on the electronic and magnetic properties of the stable scandium nitride (ScN) monolayer are investigated using first-principles calculations. The pristine monolayer is a two-dimensional (2D) indirect-gap semiconductor material with an energy gap of 1.59(2.84) eV as calculated using the GGA-PBE (HSE06) functional. The projected density of states, charge distribution, and electron localization function assert its ionic character generated by the charge transfer from the Sc atoms to the N atoms. The monolayer is magnetized by a single Sc vacancy with a total magnetic moment of 3.00µB, while a single N vacancy causes a weaker magnetization with a total magnetic moment of 0.52µB. In both cases, the magnetism originates mainly from the atoms closest to the defect site. Significant magnetization is also reached by doping with acceptor impurities. Specifically, a total magnetic moment of 2.00µB is obtained by doping with alkali metals (Li and Na) in the Sc sublattice and with B in the N sublattice. Doping with alkaline earth metals (Be and Mg) in the Sc sublattice and with C in the N sublattice induces a value of 1.00µB. In these cases, either magnetic semiconducting or half-metallicity characteristics arise in the ScN monolayer, making it a prospective 2D spintronic material. In contrast, no magnetism is induced by doping with donor impurities (O and F atoms) in the N sublattice. An O impurity metallizes the monolayer; meanwhile, F doping leads to a large band-gap reduction of the order of 82%, widening the working regime of the monolayer in optoelectronic devices. The results presented herein may introduce efficient methods to functionalize the ScN monolayer for optoelectronic and spintronic applications.

Towards understanding the first half-ALD cycle of Ag growth: adsorption and dissociation of silver(I) acetamidinates on the Ag(110) surface.

The advancement of atomic layer deposition (ALD) techniques for the controlled growth of transition metal thin films is constantly growing due to the design and synthesis of novel organometallic (OM) precursors capable of facilitating precise deposition and clean film growth. In this context, acetamidinates have emerged as a highly promising family of OM precursors due to their exceptional attributes, including outstanding stability, favorable volatility, and reactivity at low evaporation and deposition temperatures. These unique properties make them a sought-after candidate for enabling ALD processes. Here we conducted an atomic-scale study to get an in-depth understanding of the first ALD partial reaction, which involves the adsorption and dissociation process of the silver acetamidinate on the Ag(110) surface. Our research sheds light on the multistep adsorption and breaking mechanism of the novel silver(I)-N,N'-dimethylacetamidinate precursor employed as the silver source. Since the difference in energy between the monomer and dimer phases of the precursor is only 1.92 eV, we have explored the adsorption states of both phases. The monomer adsorbs on the surface by occupying hollow (H) sites; after that, it dissociates and loses its ligand, adopting a perpendicular geometry via the formation of new Ag-N bonds with the pair of N atoms at the top sites of the surface. On the other hand, the dimer adsorbs on long-bridge sites (LB) with the pair of N atoms occupying top sites with the silver atoms from the surface. Next, the dimer loses a pair of N-Ag bonds on each ligand, reaching a more stable state of partial cleavage with a relative energy of -0.38 eV. After overcoming an energy barrier of 0.41 eV, the dimer loses the remaining pair of N-Ag bonds, and the silver atoms diffuse towards H sites. Finally, the ligands diffuse toward the adjacent channel in the [100] direction of the surface. A charge distribution analysis of the adsorption stages shows the evolution of the silver atoms from precursor to the metallic state.

Antiferromagnetism in GaS monolayer doped with TM-TM atom pairs (TM = V, Cr, Mn, and Fe).

In this work, structural modification at Ga sites of the gallium sulfide (GaS) monolayer is explored to create new two-dimensional (2D) materials towards spintronic applications. GaS monolayer is a non-magnetic indirect-gap semiconductor material with an energy gap of 2.38 (3.27) eV as calculated using the PBE(HSE06) functional. Half-metallicity is induced in this 2D material by creating a single Ga vacancy, where S atoms around the defect site produce mainly the magnetic properties with a total magnetic moment of 1.00µB. In contrast, the non-magnetic nature is preserved under the effects of a pair of Ga vacancies, which metallize the monolayer. V, Mn, and Fe doping leads to the emergence of the diluted magnetic semiconductor nature, while doping with Cr creates a new 2D half-metallic material from the GaS monolayer. In these cases, total magnetic moments between 2.00 and 5.00µB are obtained and the 3d orbital of transition metal (TM) impurities mainly induces the system magnetism. In addition, the effects of doping with a pair of TM (pTM) atoms are also investigated, in which the antiferromagnetism is found to be stable rather than the ferromagnetism to follow the Pauli exclusion principle. Significant magnetization of the GaS monolayer is also achieved with zero total magnetic moment because of the structural mirror-symmetry. pV-, pMn-, and pFe-doped systems are antiferromagnetic semiconductor materials with energy gaps of 1.06, 1.90, and 1.84 eV, respectively. Meanwhile, the monolayer is metallized by doping with a pCr pair. The results presented herein indicate that the defective and doped GaS monolayers are prospective 2D candidates for spintronic applications - which are hindered for the pristine GaS monolayer because of the absence of intrinsic magnetism.

A systematic investigation of chromium and vanadium impurities in a Janus Ga2SO monolayer towards spintronic applications.

Transition metals (TMs) have been employed as efficient sources of magnetism in non-magnetic two-dimensional (2D) materials. In this work, doping with chromium (Cr) and vanadium (V) is proposed to induce feature-rich electronic and magnetic properties in a Janus Ga2SO monolayer towards spintronic applications. The Ga2SO monolayer is a 2D semiconductor material with an energy gap of 1.30 (2.12) eV obtained from PBE(HSE06)-based calculations. Considering the structural asymmetry, different vacancy and doping sites are considered. A single Ga vacancy and pair of Ga vacancies magnetize the monolayer with total magnetic moments between 0.69 and 3.13µB, where the half-metallic nature is induced by the single Ga1 vacancy (that bound to the S atom). In these cases, the magnetism is originated mainly from S and O atoms closest to the vacancy sites. Depending on the doping site, either half-metallicity or diluted magnetic semiconductor natures are obtained by doping with Cr and V atoms with total magnetic moments of 3.00 and 2.00µB, respectively. Herein, 3d TM impurities produce mainly the system magnetism. When substituting a pair of Ga atoms, TM atoms exhibit the antiparallel spin alignment to follow the Pauli exclusion principle, retaining the novel electronic characteristics induced by a single TM dopant. Except for the case of doping with a pair of V atoms, total magnetic moments of 2.00 and 1.00µB are obtained by doping with a pair or Cr atoms and Cr/V co-doping, respectively. The non-zero magnetic moment is derived from the different interactions of each TM atom with its neighboring atoms, which will also be studied by Bader charge analysis. Our results introduce new promising 2D spintronic candidates, which are made by structural modifications at Ga sites of a non-magnetic Janus Ga2SO monolayer.

A surge of light at the birth of a supernova.

It is difficult to establish the properties of massive stars that explode as supernovae. The electromagnetic emission during the first minutes to hours after the emergence of the shock from the stellar surface conveys important information about the final evolution and structure of the exploding star. However, the unpredictable nature of supernova events hinders the detection of this brief initial phase. Here we report the serendipitous discovery of a newly born, normal type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical wavelengths of about 40 magnitudes per day. The very frequent sampling of the observations allowed us to study in detail the outermost structure of the progenitor of the supernova and the physics of the emergence of the shock. We develop hydrodynamical models of the explosion that naturally account for the complete evolution of the supernova over distinct phases regulated by different physical processes. This result suggests that it is appropriate to decouple the treatment of the shock propagation from the unknown mechanism that triggers the explosion.

Fertility in seasonal-calving pasture-based lactating dairy cows following timed artificial insemination or timed embryo transfer with fresh or frozen in vitro-produced embryos.

The objective was to compare pregnancy per service event (P/S) in lactating dairy cows following timed artificial insemination (AI) or timed embryo transfer (ET) using either fresh or frozen in vitro-produced embryos. Oocytes were collected once per week for up to 9 wk using transvaginal ovum pick-up from elite dairy donors (ET-DAIRY; n = 40; Holstein-Friesian and Jersey) and elite beef donors (ET-ELITE-BEEF; n = 21; Angus). Both ET-DAIRY and ET-ELITE-BEEF donors consisted of heifers and cows. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (ET-COMM-BEEF; n = 119). Following in vitro maturation and fertilization, presumptive zygotes were cultured in vitro to the blastocyst stage. Grade 1 blastocysts were either transferred fresh or frozen for on-farm thawing and direct transfer. A total of 1,106 recipient cows (all lactating, predominantly Holstein-Friesian) located on 16 herdlets were blocked based on parity, calving date, and Economic Breeding Index, and randomly assigned to receive AI (n = 243) or ET (n = 863) after estrous synchronization with a 10-d Progesterone-synch protocol. Cows assigned to ET were further randomized to receive fresh (n = 187) or frozen (n = 178) ET-ELITE-BEEF embryos, fresh (n = 169) or frozen (n = 162) ET-DAIRY embryos, or fresh (n = 80) or frozen (n = 87) ET-COMM-BEEF embryos. Pregnancy was diagnosed using transrectal ultrasound on d 32 to 35 after synchronized ovulation and confirmed on d 62 to 65, at which time fetal sex was determined. Pregnancy per service event at d 32 was not different between AI (48.8%) and ET (48.9%) and did not differ between dairy and beef embryos (50.3% vs. 48.1%, respectively). However, P/S was less on d 32 following transfer of frozen embryos (41.6%) compared with fresh embryos (56.1%). Pregnancy loss between d 32 and 62 was greater for ET (15.1%) compared with AI (4.7%), with greater losses observed for frozen beef (18.5%), fresh beef (17.3%), and frozen dairy (19.2%) compared with fresh dairy (6.0%) embryos. Serum progesterone (P4) concentration on d 7 was associated with P/S at d 32 and 62. Cows in the quartile with the least serum P4 concentrations (quartile 1) had less probability of being pregnant on d 32 (33.4%) compared with cows in the 3 upper quartiles for serum P4 (45.7%, 55.6%, and 61.2% for quartile 2, quartile 3, and quartile 4, respectively). Sex ratio (male:female) at d 62 was skewed toward more male fetuses following ET (61.1:38.9) compared with AI (43.2:56.8) and was consistent with the sex ratio among in vitro blastocysts (61.2:38.8). In conclusion, P/S was similar for AI and ET, although pregnancy loss between d 32 and 62 was greater for ET than for AI.

Associations among antimicrobial use, calf management practices, and antimicrobial resistance in Escherichia coli from a pooled fecal sample in calves on Canadian dairy farms: A cross-sectional study.

The objective of this cross-sectional study was to determine associations between calf management practices, the number of antimicrobial treatments, and antimicrobial resistance in preweaning heifers on Canadian dairy farms. A composite of 5 fecal samples from preweaning calves was collected from 142 dairy farms in 5 provinces and analyzed for phenotypic antimicrobial susceptibility with the microbroth dilution method. Questionnaires were used to capture herd characteristics and calf management practices used on the farm. Calf treatment records were collected during the farm visits. Escherichia coli was isolated from all 142 fecal samples with the highest resistance to tetracycline (41%), followed by sulfisoxazole (36%), streptomycin (32%), chloramphenicol (28%), ampicillin (16%), trimethoprim-sulfamethoxazole (15%), ceftriaxone (4.2%), cefoxitin (2.8%), amoxicillin-clavulanic acid (2.1%), ciprofloxacin (2.1%), nalidixic acid (2.1%), azithromycin (1.4%), and gentamicin (1.4%). Multidrug resistance was observed in 37% of E. coli isolates. Three-quarters of farms used fresh colostrum as the most common type of colostrum fed to calves. Colostrum quality was checked on 49% of farms, but the transfer of passive immunity was only checked on 32% of farms in the last 12 mo. Almost 70% of farms used straw or hay or a combination as the bedding material for calves. Among the 142 farms, a complete set of calf records were collected from 71 farms. In a multivariable logistic regression model, farms with ≥1.99 to 32.57 antimicrobial treatments/calf-year were 3.2 times more likely to have multidrug resistant E. coli in calf feces compared farms with <1.99 antimicrobial treatments/calf-year. Farms using hay or straw beddings were 5.1 times less likely to have multidrug resistant E. coli compared with those with other bedding materials including shavings or sawdust. Bedding management practices on farms may need to be investigated to reduce the potential effect on disseminating multidrug resistant bacteria.

Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths.

BACKGROUND: Mesophotic coral communities are increasingly gaining attention for the unique biological diversity they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies on corals have rarely included mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. RESULTS: Here, we used reduced-representation genome sequencing to conduct a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed deep divergences within the two genera and undescribed diversity across the current taxonomic species. Five of the eight focal species consisted of at least two sympatric and genetically distinct lineages, which were consistently detected across different methods. CONCLUSIONS: The repeated observation of genetically divergent lineages associated with mesophotic depths highlights that there may be many more mesophotic-specialist coral species than currently acknowledged and that an urgent assessment of this largely unstudied biological diversity is warranted.

Diagnostic accuracy of patch testing based in clinical response to contact allergen restrictions in allergic contact dermatitis.

Summary: Background. Patch testing (PT) is used to identify substances that cause allergic contact dermatitis (ACD). However, the clinical effects of allergen restrictions following PT have not been thoroughly investigated. This study aims to assess the diagnostic accuracy of PT in patients suspected of having ACD. Methods. Prospective study. PT were performed in patients with clinical diagnosis of ACD. Patients with a positive PT (case group) had a strict restriction of the suspected substance for one month. In patients with negative patch testing (control group), allergen restriction was based in clinical history. Clinical reduction (CR) of at least 50% in disease activity (CR50%) after one month of allergen restriction was considered clinically relevant. Total control was defined as clinical reduction of at least 90% (CR90%). Results. From 400 patients, 66.2% had a positive PT. The sensitivity of PT to identify CR50% was 84%, specificity 47%, PPV 53%, and NPV 81%. Only 10.5% of patients achieved CR90%. Conclusions. The PT had moderate diagnostic accuracy. It could be useful as a screening, but a positive result should be confirmed with controlled allergen restriction. The low number of patients who achieved a 90% CR invites to reconsider the allergens included in PT and the mechanistic processes of the disease.

Genomic-wide analysis approach revealed genomic similarity for environmental Mexican S. Oranienburg genomes.

As the human population grows, an increase in food trade is needed. This elevates the risk of epidemiological outbreaks. One of the prevalent pathogens associated with food production in Mexico has been Salmonella Oranienburg. Effective surveillance systems require microbial genetic knowledge. The objective of this work is to describe the genetic composition of Mexican S. Oranienburg genomes. For that, 53 strains from different environmental sources were isolated and sequenced. Additionally, 109 S. Oranienburg genomes were downloaded. Bioinformatic analyses were used to explore the clonal complex and genomic relatedness. A major clonal group formed by ST23 was identified comprising four STs. 202 SNPs were found the maximum difference among isolates. Virulence genes for host invasion and colonization as rpoS, fimbria type 1, and, T3SS were found common for all isolates. This study suggests that Mexican S. Oranienburg strains are potential pathogens circulating continuously in the region between host and non-host environments.

Changes in the Location of Cutaneous Melanoma Over the Past 30 Years. A Retrospective Observational Study. / Cambios en la localización del melanoma cutáneo en los últimos 30 años. Estudio observacional retrospectivo.

BACKGROUND: The location of cutaneous melanoma is associated with photoexposure. OBJECTIVES: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years. PATIENTS AND METHODS: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017. RESULTS: A total of 1,937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p <0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p <0.001), and in the trunk men (57.5% vs 47.3%, p=0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant. CONCLUSION: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes.

Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study. / Percepción de la mujer con psoriasis en la planificación familiar: Estudio descriptivo, transversal y multicéntrico.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

[Translated article] Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

Broodstock nutritional programming differentially affects the hepatic transcriptome and genome-wide DNA methylome of farmed gilthead sea bream (Sparus aurata) depending on genetic background.

BACKGROUND: Broodstock nutritional programming improves the offspring utilization of plant-based diets in gilthead sea bream through changes in hepatic metabolism. Attention was initially focused on fatty acid desaturases, but it can involve a wide range of processes that remain largely unexplored. How all this can be driven by a different genetic background is hardly underlined, and the present study aimed to assess how broodstock nutrition affects differentially the transcriptome and genome-wide DNA methylome of reference and genetically selected fish within the PROGENSA® selection program. RESULTS: After the stimulus phase with a low fish oil diet, two offspring subsets of each genetic background received a control or a FUTURE-based diet. This highlighted a different hepatic transcriptome (RNA-seq) and genome-wide DNA methylation (MBD-seq) pattern depending on the genetic background. The number of differentially expressed transcripts following the challenge phase varied from 323 in reference fish to 2,009 in genetically selected fish. The number of discriminant transcripts, and associated enriched functions, were also markedly higher in selected fish. Moreover, correlation analysis depicted a hyper-methylated and down-regulated gene expression state in selected fish with the FUTURE diet, whereas the opposite pattern appeared in reference fish. After filtering for highly represented functions in selected fish, 115 epigenetic markers were retrieved in this group. Among them, lipid metabolism genes (23) were the most reactive following ordering by fold-change in expression, rendering a final list of 10 top markers with a key role on hepatic lipogenesis and fatty acid metabolism (cd36, pitpna, cidea, fasn, g6pd, lipt1, scd1a, acsbg2, acsl14, acsbg2). CONCLUSIONS: Gene expression profiles and methylation signatures were dependent on genetic background in our experimental model. Such assumption affected the magnitude, but also the type and direction of change. Thus, the resulting epigenetic clock of reference fish might depict an older phenotype with a lower methylation for the epigenetically responsive genes with a negative methylation-expression pattern. Therefore, epigenetic markers will be specific of each genetic lineage, serving the broodstock programming in our selected fish to prevent and mitigate later in life the risk of hepatic steatosis through changes in hepatic lipogenesis and fatty acid metabolism.

Using Human Induced Pluripotent Stem Cell-Derived Organoids to Identify New Pathologies in Patients With PDX1 Mutations.

BACKGROUND & AIMS: Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1188delC/188delC patients. METHODS: Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1188delC/188delC patient and an isogenic induced pluripotent stem cell line where the PDX1 point mutation was corrected. RESULTS: Patient-derived PDX1188delC/188delC antral organoids exhibited an intestinal phenotype, whereas intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsy specimens from both PDX1188delC/188delC patients, which recapitulated the organoid phenotypes. Moreover, antral biopsy specimens also showed increased parietal cells and lacked G cells, suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. CONCLUSIONS: These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.

Constraint of the Nuclear Dissipation Coefficient in Fission of Hypernuclei.

Experimental studies of nuclear fission induced by fusion, transfer, spallation, fragmentation, and electromagnetic reactions in combination with state-of-the-art calculations are successful to investigate the nuclear dissipation mechanism in normal nuclear matter, containing only nucleons. The dissipation mechanism has been widely studied by the use of many different fission observables and nowadays the dissipation coefficients involved in transport theories are well constrained. However, the existence of hypernuclei and the possible presence of hyperons in neutron stars make it necessary to extend the investigation of the nuclear dissipation coefficient to the strangeness sector. In this Letter, we use fission reactions of hypernuclei to constrain for the first time the dissipation coefficient in hypernuclear matter, observing that this coefficient increases a factor of 6 in the presence of a single Λ hyperon with respect to normal nuclear matter.