CONSTANS, a HUB for all seasons: How photoperiod pervades plant physiology regulatory circuits.

How does a plant detect the changing seasons and make important developmental decisions accordingly? How do they incorporate daylength information into their routine physiological processes? Photoperiodism, or the capacity to measure the daylength, is a crucial aspect of plant development that helps plants determine the best time of the year to make vital decisions, such as flowering. The protein CONSTANS (CO) constitutes the central regulator of this sensing mechanism, not only activating florigen production in the leaves but also participating in many physiological aspects in which seasonality is important. Recent discoveries place CO in the center of a gene network that can determine the length of the day and confer seasonal input to aspects of plant development and physiology as important as senescence, seed size, or circadian rhythms. In this review, we discuss the importance of CO protein structure, function, and evolutionary mechanisms that embryophytes have developed to incorporate annual information into their physiology.

Composition and optical properties of (In, Ga)As nanowires grown by group-III-assisted molecular beam epitaxy.

(In, Ga) alloy droplets are used to catalyse the growth of (In, Ga)As nanowires by molecular beam epitaxy on Si(111) substrates. The composition, morphology and optical properties of these nanowires can be tuned by the employed elemental fluxes. To incorporate more than 10% of In, a high In/(In+Ga) flux ratio above 0.7 is required. We report a maximum In content of almost 30% in bulk (In, Ga)As nanowires for an In/(In+Ga) flux ratio of 0.8. However, with increasing In/(In+Ga) flux ratio, the nanowire length and diameter are notably reduced. Using photoluminescence and cathodoluminescence spectroscopy on nanowires covered by a passivating (In, Al)As shell, two luminescence bands are observed. A significant segment of the nanowires shows homogeneous emission, with a wavelength corresponding to the In content in this segment, while the consumption of the catalyst droplet leads to a spectrally-shifted emission band at the top of the nanowires. The (In,Ga)As nanowires studied in this work provide a new approach for the integration of infrared emitters on Si platforms.

Response of Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae) parasitized by the nematode Metaparasitylenchus hypothenemi Poinar (Tylenchida: Allantonematidae) to different colors of light.

Metaparasitylenchus hypothenemi is a nematode that naturally parasitizes Hypothenemus hampei in a coffee-producing region in Chiapas, Mexico. This study investigated changes in the attraction of parasitized borers to light. We compared the attraction of adult H. hampei females (parasitized and uninfected) to 14 different light wavelengths (350-670 nm) with a control (570 nm, yellow) under laboratory conditions. The response ranges of non-parasitized and parasitized borers were 370-650 nm and 340-650 nm, respectively. The attraction curve showed a similar shape in both borer groups (parasitized and non-parasitized), but a wide wavelength range (380-590 nm) attracted more parasitized than non-parasitized borers. The maximum response of the uninfected borers occurred at 520 nm (green), while parasitized borers exhibited three response peaks (380 nm, violet; 460 nm, blue; 520 nm, green). Parasitized borers were significantly more attracted to green light (520 nm) than to the control. The altered attraction to light in borers parasitized by M. hypothenemi is discussed from the perspective of possible host manipulation and the natural prevalence of this parasite.

Persulfidation protects from oxidative stress under nonphotorespiratory conditions in Arabidopsis.

Hydrogen sulfide is a signaling molecule in plants that regulates essential biological processes through protein persulfidation. However, little is known about sulfide-mediated regulation in relation to photorespiration. Here, we performed label-free quantitative proteomic analysis and observed a high impact on protein persulfidation levels when plants grown under nonphotorespiratory conditions were transferred to air, with 98.7% of the identified proteins being more persulfidated under suppressed photorespiration. Interestingly, a higher level of reactive oxygen species (ROS) was detected under nonphotorespiratory conditions. Analysis of the effect of sulfide on aspects associated with non- or photorespiratory growth conditions has demonstrated that it protects plants grown under suppressed photorespiration. Thus, sulfide amends the imbalance of carbon/nitrogen and restores ATP levels to concentrations like those of air-grown plants; balances the high level of ROS in plants under nonphotorespiratory conditions to reach a cellular redox state similar to that in air-grown plants; and regulates stomatal closure, to decrease the high guard cell ROS levels and induce stomatal aperture. In this way, sulfide signals the CO2 -dependent stomata movement, in the opposite direction of the established abscisic acid-dependent movement. Our findings suggest that the high persulfidation level under suppressed photorespiration reveals an essential role of sulfide signaling under these conditions.

Hydrogen-Induced Ultralow Optical Absorption and Mechanical Loss in Amorphous Silicon for Gravitational-Wave Detectors.

The sensitivity of gravitational-wave detectors is limited by the mechanical loss associated with the amorphous coatings of the detectors' mirrors. Amorphous silicon has higher refraction index and lower mechanical loss than current high-index coatings, but its optical absorption at the wavelength used for the detectors is at present large. The addition of hydrogen to the amorphous silicon network reduces both optical absorption and mechanical loss for films prepared under a range of conditions at all measured wavelengths and temperatures, with a particularly large effect on films grown at room temperature. The uptake of hydrogen is greatest in the films grown at room temperature, but still below 1.5 at.% H, which show an ultralow optical absorption (below 10 ppm) measured at 2000 nm for 500-nm-thick films. These results show that hydrogenation is a promising strategy to reduce both optical absorption and mechanical loss in amorphous silicon, and may enable fabrication of mirror coatings for gravitational-wave detectors with improved sensitivity.

Growth kinetics and substrate stability during high-temperature molecular beam epitaxy of AlN nanowires.

We study the molecular beam epitaxy of AlN nanowires between 950 °C and 1215 °C, well above the usual growth temperatures, to identify optimal growth conditions. The nanowires are grown by self-assembly on TiN(111) films sputtered onto Al2O3. Above 1100 °C, the TiN film is seen to undergo grain growth and its surface exhibits {111} facets where AlN nucleation preferentially occurs. Modeling of the nanowire elongation rate measured at different temperatures shows that the Al adatom diffusion length maximizes at 1150 °C, which appears to be the optimum growth temperature. However, analysis of the nanowire luminescence shows a steep increase in the deep-level signal already above 1050 °C, associated with O incorporation from the Al2O3substrate. Comparison with AlN nanowires grown on Si, MgO and SiC substrates suggests that heavy doping of Si and O by interdiffusion from the TiN/substrate interface increases the nanowire internal quantum efficiency, presumably due to the formation of a SiNxor AlOxpassivation shell. The outdiffusion of Si and O would also cause the formation of the inversion domains observed in the nanowires. It follows that for optoelectronic and piezoelectric applications, optimal AlN nanowire ensembles should be prepared at 1150 °C on TiN/SiC substrates and will require anex situsurface passivation.

Improvement of Magnetic Saturation in Fe3O4@Y2O3:Eu3+ Nanocomposites Through the Manipulation of Eu3+ Activators.

Fe3O4@Y2O3:Eu3+ nanocomposites and Y2O3:Eu3+ nanophosphors were synthesized using the hydrothermal method. Nanocomposites were analyzed using X-ray diffraction (XRD), Rietveld refinements, Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, photoluminescence (PL), vibrating sample magnetometer (VSM), and high-resolution transmission electron microscopy (HRTEM). Nanocomposites exhibit superparamagnetic behavior that improves with Eu3+, resulting in increased magnetic saturation. In contrast to Y2O3:Eu3+ nanophosphors, the Fe3O4@Y2O3:Eu3+ nanocomposites display a distinctive characteristic whereby the photoluminescence intensity increases with a reduced concentration of Eu3+. The requirement of increasing the thickness of the Y2O3:Eu3+ outer layer to achieve improved light emission can be circumvented by solely manipulating the concentration of activators, without compromising the magnetic saturation of the nanocomposites. The luminescent and magnetic characteristics of Fe3O4@Y2O3:Eu3+ nanocomposites can be readily optimized using straightforward synthesis parameters, making them promising candidates for potential applications in theranostic medicine.

Determination of soluble tumor necrosis factor receptor II and secretory immunoglobulin A in saliva of patients with dementia.

The prevalence of pain and dementia increases with age, affecting a significant percentage of the population due to aging. Both pathologies are connected through the inflammatory process, specifically through the tumor necrosis factor. The effect of this cytokine is mediated through the modulation of its TNFRI and TNFRII receptors, which are linked to the dementia process. In addition, immunoglobulins such as secretory immunoglobulin A (sIgA) have been recognized as one of the main biomarkers of pain in saliva. sTNFRII and sIgA levels were determined in saliva samples by ELISA from healthy people and patients with dementia in GDS stages 5-7. The concentrations of these markers were also correlated with the GDS stage and sex. We observed a significant decrease (*** p ≤ 0.001) in the levels of sTNFRII (pg/mL) and a significant increase (** p ≤ 0.01) in the levels of sIgA (ng/mL) in the saliva of patients with dementia compared to the healthy control group. We did not observe a correlation with the data of the biomarkers regarding the GDS stage and sex. The results obtained for sTNFRII are consistent with those obtained by other authors on brain tissue, who conclude that unopposed neuronal TNFRI signaling, when TNFRII is selectively downregulated, leads to a more severe course of AD pathogenesis. Regarding sIgA, the elevated values of sIgA may reflect the immune status of these patients. Therefore, these biomarkers can provide us with relevant information through a non-invasive method such as saliva analysis.

Incidental maternal findings on fetal MRI.

AIM: To evaluate the type and frequency of maternal findings incidentally identified during fetal magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective single-centre study was undertaken which included all consecutive fetal MRI studies performed between July 2017 and May 2021 at a tertiary institution. Two fellowship-trained radiologists reviewed the studies independently to determine the type and frequency of incidental maternal findings of both no clinical significance (requiring no further follow-up) and of clinical significance (requiring further follow-up, work-up, and/or management). Differences in acquisition were resolved by two-reader consensus. Non-diagnostic MRI examinations or abdominal MRI examinations indicated for maternal complications were excluded from review. RESULTS: A total of 455 consecutive fetal MRI examinations performed in 429 women were included. Mean age was 30 years (SD 5.5 years). At least one incidental maternal finding was identified in 58% (265/455) of studies. Umbilical hernias (35%), maternal hydronephrosis (19%), and maternal hydro-ureter (15%) were the most common. Only two studies (0.5%) showed clinically significant incidental maternal findings (pancreatic pseudocyst and ovarian cyst). CONCLUSIONS: Incidental maternal findings are common on fetal MRI but rarely require further follow-up, work-up, and/or management.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Oral and general health conditions involved in periodontal status during pregnancy: a prospective cohort study.

PURPOSE: Pregnancy is a period in a woman's life that has important consequences on oral health, particularly for gingival health. Present study aims to identify women at higher risk of developing periodontal disease (gingivitis and periodontitis) during late pregnancy and evaluate how this condition evolves during this period. METHODS: Prospective cohort study was designed with pregnant women who were assessed during the first and third trimesters of gestation in a southern Spanish public hospital. Data regarding gingival and periodontal health, oral hygiene, and overall health status (obesity and diabetes mellitus) were collected. Reporting followed STROBE checklist. RESULTS: Significantly higher number of women had the periodontal and gingival disease in the third trimester of gestation compared with in early pregnancy. In the third trimester of gestation, 42 (28.6%) and 63 (42.9%) of women presented symptoms of periodontal disease and gingival disease, respectively. Obesity (OR 2.834; 95%CI 0.919-8.741), worse oral hygiene during the first trimester of gestation (OR: 4.031; 95%CI 2.12-7.65), and periodontal disease during early pregnancy (OR: 15.104; 95%CI 3.60-63.36) most effectively predicted periodontal disease during late pregnancy. CONCLUSIONS: Pregnancy is associated with exacerbated periodontal and gingival disease symptoms throughout the different trimesters of gestation. Obesity and oral hygiene during early pregnancy were the risk factors that most contributed to the aforementioned changes in periodontal disease.

Regulation of CO2 by the sea in areas around Latin America in a context of climate change.

Anthropogenic activities are increasing the atmospheric carbon dioxide (CO2); around a third of the CO2 emitted by these activities has been taken up by the ocean. Nevertheless, this marine ecosystem service of regulation remains largely invisible to society, and not enough is known about regional differences and trends in sea-air CO2 fluxes (FCO2), especially in the Southern Hemisphere. The objectives of this work were as follows: first to put values of FCO2 integrated over the exclusive economic zones (EEZ) of five Latin-American countries (Argentina, Brazil, Mexico, Peru, and Venezuela) into perspective regarding total country-level greenhouse gases (GHG) emissions. Second, to assess the variability of two main biological factors affecting FCO2 at marine ecological time series (METS) in these areas. FCO2 over the EEZs were estimated using the NEMO model, and GHG emissions were taken from reports to the UN Framework Convention on Climate Change. For each METS, the variability in phytoplankton biomass (indexed by chlorophyll-a concentration, Chla) and abundance of different cell sizes (phy-size) were analyzed at two time periods (2000-2015 and 2007-2015). Estimates of FCO2 at the analyzed EEZs showed high variability among each other and non-negligible values in the context of greenhouse gas emissions. The trends observed at the METS indicated, in some cases, an increase in Chla (e.g., EPEA-Argentina) and a decrease in others (e.g., IMARPE-Peru). Evidence of increasing populations of small size-phytoplankton was observed (e.g., EPEA-Argentina, Ensenada-Mexico), which would affect the carbon export to the deep ocean. These results highlight the relevance of ocean health and its ecosystem service of regulation when discussing carbon net emissions and budgets.

Assessment of the periodontal health status and gingival recession during orthodontic treatment with clear aligners and fixed appliances: A systematic review and meta-analysis.

BACKGROUND: The aim was to assess periodontal health maintenance and gingival recessions development in patients undergoing an orthodontic treatment with clear aligners (CA) and fixed appliances (FA). MATERIAL AND METHODS: An electronic search in MEDLINE, Scopus, The Cochrane Library, and Web of Science was performed up to September 2022 to identify all potential articles. Two investigators independently selected the studies according to the inclusion criteria. Prospective and retrospective studies assessing the periodontal health status and gingival recession development during the orthodontic treatment with buccal FA and CA were included. Case series, cross-sectional studies, and studies with less than two months of follow-up were excluded. Two investigators independently extracted the data from included articles and assessed risk of bias across studies using the Cochrane Collaboration tool. Qualitative and quantitative analyses of the data were performed. Pairwise meta-analysis using a random-effects model were used to compare periodontal indices between FA and CA treatment in different follow-up periods. RESULTS: From the 129 potential studies, finally 12 studies were included. Only 8 could be included in the quantitative analysis. CA seems to slightly maintain better periodontal health indices. Only plaque index in a mid-term follow-up (mean difference (MD): -0.99; 95%; Confidence interval (CI) [-1.94 to -0.03]; P=.04; I2=99%), and pocket probing depth at a long-term follow-up (MD: -0.93mm; 95% CI [-1.16 to 0.7]; P<0.0001) reported statistically significant results favoring CA. CONCLUSIONS: Up to the date there is not enough evidence to conclude that CA maintains better periodontal health during an orthodontic treatment than FA.

Effect of the buccal fat pad in the prevention of zygomatic implant surgery postoperative complications: A pilot study.

BACKGROUND: Zygomatic implants have been used to treat severe atrophy maxilla. Since its description, the technique has been improved in order to reduce patient morbidity as well as prosthesis rehabilitation time. Despite the improvements in the procedure, zygomatic implant treatments still have complications related to the peri-implant soft-tissue; a probing depth greater than 6 millimeter (mm) and a prevalence of bleeding on probing of 45% have been described. The mobilization of the buccal fat has been used to manage different oral and maxillofacial soft-tissue pathologies. The aim of this study was to assess whether the buccal fat pad might prevent mucosal dehiscence and avoid potential postoperative complications when is placed covering the body part of the zygomatic implants. MATERIAL AND METHODS: In this pilot study, 7 patients were enrolled and a total of 28 zygomatic implants were placed and evaluated during a 12-month follow-up period. Surgical sites were randomly divided into two groups before implant placement: control group (A; in which no buccal fat pad was applied) and experimental group (B). Peri-implant soft tissue thickness difference, pain using a Visual Analog Scale (VAS), swelling, hematoma, buccal soft tissue healing and sinusitis, were evaluated. The implant survival rate was determined according the Aparicio success criteria and compared between the control and experimental procedure. RESULTS: A nonstatistical difference was found between groups regarding to pain. The experimental group showed higher soft-tissues thickness (p= 0.03) and the implant survival rate was 100% in both groups. CONCLUSIONS: The mobilization of the buccal fat pad to cover the body of the zygomatic implants increases peri-implant soft-tissue thickness, without increasing the postoperative pain.

A 2-year follow-up of a novel Fracture Liaison Service: can we reduce the mortality in elderly hip fracture patients? A prospective cohort study.

Osteoporosis is an underdiagnosed disease that results in bone fragility and risk of fractures. Fracture Liaison Service (FLS) is a secondary prevention model which identifies patients at risk for fragility fractures. The introduction of a FLS protocol showed an increase of anti-osteoporotic drug prescription and significant reduction of all-cause mortality. INTRODUCTION: Hip fractures are the most severe osteoporotic fracture due to their associated disability and elevated risk of mortality. FLS programs have enhanced the management of osteoporosis-related fractures. Our objective is to analyze the effect of the FLS model over survival and 2-year mortality rate following a hip fracture. METHODS: We conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture during 3 consecutive years, before and after the implementation of the FLS in our center (i.e., between January 2016 and December 2018). Patients' information was withdrawn from our local computerized database. Patients were followed for 2 years after the hip fracture. Mortality and re-fracture rates were compared between the two groups using a multivariate Cox proportional hazard model. RESULTS: A total of 1101 patients were included in this study (i.e., 357 before FLS implementation and 744 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (583 (78.4%) vs 44 (12.3%); p < 0.01). There was an increase of adherence to treatment after FLS implementation (227 (38.9%) vs 12 (3.3%); p = 0.03). A total of 222 (29.8%) patients after FLS implementation and 114 (31.9%) individuals before FLS implementation (p = 0.44) died during the follow-up period. A second fracture occurred in 49 (6.6%) patients after FLS implementation and in 26 (7.3%) individuals before FLS implementation (p = 0.65). Patients who were treated with anti-osteoporotic drugs after the implementation of the FLS protocol had a lower all-cause 1-year and 2-year mortality compared with patients managed before the implementation of the FLS protocol (adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59-0.96; HR 0.87, 95% CI 0.69-1.09, respectively). CONCLUSIONS: The implementation of a FLS protocol was associated with an increase of anti-osteoporotic treatment, higher adherence, and greater survival in elderly hip fracture patients. There was a significant reduction of all-cause mortality in the FLS patients treated with anti-osteoporotic. However, the application of the FLS did not affect the risk of suffering a second fragility fracture.

bZIP transcription factors PcYap1 and PcRsmA link oxidative stress response to secondary metabolism and development in Penicillium chrysogenum.

BACKGROUND: Reactive oxygen species (ROS) trigger different morphogenic processes in filamentous fungi and have been shown to play a role in the regulation of the biosynthesis of some secondary metabolites. Some bZIP transcription factors, such as Yap1, AtfA and AtfB, mediate resistance to oxidative stress and have a role in secondary metabolism regulation. In this work we aimed to get insight into the molecular basis of this regulation in the industrially important fungus Penicillium chrysogenum through the characterization of the role played by two effectors that mediate the oxidative stress response in development and secondary metabolism. RESULTS: In P. chrysogenum, penicillin biosynthesis and conidiation are stimulated by the addition of H2O2 to the culture medium, and this effect is mediated by the bZIP transcription factors PcYap1 and PcRsmA. Silencing of expression of both proteins by RNAi resulted in similar phenotypes, characterized by increased levels of ROS in the cell, reduced conidiation, higher sensitivity of conidia to H2O2 and a decrease in penicillin production. Both PcYap1 and PcRsmA are able to sense H2O2-generated ROS in vitro and change its conformation in response to this stimulus. PcYap1 and PcRsmA positively regulate the expression of brlA, the first gene of the conidiation central regulatory pathway. PcYap1 binds in vitro to a previously identified regulatory sequence in the promoter of the penicillin gene pcbAB: TTAGTAA, and to a TTACTAA sequence in the promoter of the brlA gene, whereas PcRsmA binds to the sequences TGAGACA and TTACGTAA (CRE motif) in the promoters of the pcbAB and penDE genes, respectively. CONCLUSIONS: bZIP transcription factors PcYap1 and PcRsmA respond to the presence of H2O2-generated ROS and regulate oxidative stress response in the cell. Both proteins mediate ROS regulation of penicillin biosynthesis and conidiation by binding to specific regulatory elements in the promoters of key genes. PcYap1 is identified as the previously proposed transcription factor PTA1 (Penicillin Transcriptional Activator 1), which binds to the regulatory sequence TTAGTAA in the pcbAB gene promoter. This is the first report of a Yap1 protein directly regulating transcription of a secondary metabolism gene. A model describing the regulatory network mediated by PcYap1 and PcRsmA is proposed.

Murine colonization model by Campylobacter coli DSPV458.

AIMS: To generate a murine experimental model of colonization by Campylobacter coli DSPV458. METHODS AND RESULTS: Twelve adult Balb/cCmedc female mice were housed in a treated group (T-G) and a control group (C-G) for 4 weeks. Both experimental groups received antibiotics for 5 days during the first week. The T-G was administered with 6.68log10 CFU of C. coli DSPV458 by oesophageal gavage. Necropsies were performed weekly to evaluate translocation and intestinal colonization in the spleen and liver and in the ileum and cecum respectively. Samples were cultured to quantify intestinal microbiota members. Faeces were cultured weekly for a C. coli DSPV458 count. Campylobacter coli DSPV458 was isolated from all the inoculated mice. The recovered level of C. coli DSPV458 was, on average, 6.9 log10 CFUg-1 , 8.0 log10 CFUg-1 and 1.6 log10 CFUg-1 in faeces, cecum and ileum respectively. Colonization by C. coli DSPV458 does not alter the normal clinical and physiological status. CONCLUSIONS: Campylobacter coli DSPV458 does not have an invasive capacity, and the model is suitable for evaluating strategies to reduce intestinal loads. SIGNIFICANCE AND IMPACT OF STUDY: Farm animals have an important impact on thermotolerant Campylobacter transmission to humans. Extremely few colonization models by C. coli have been reported to date. In food-producing animals, infection is mild or absent and thermotolerant Campylobacter colonize the intestines of animals. Colonization models are specific models that do not cause infection as they do not generally result in diarrhoea or other signs of disease. Therefore, this model will allow to evaluate the evolution of colonization by thermotolerant Campylobacter and the alternative tools development to antibiotics that limit their colonization in food-producing animals.

An improved limit on the charge of antihydrogen from stochastic acceleration.

Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.

Inguinal lymph nodes agenesia in a patient with Schimmelpenning-Feuerstein-Mims syndrome with proven somatic KRAS mutation.

Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a neurocutaneous disorder that can affect many body systems. The principal and most characteristic anomalies are craniofacial naevus sebaceous in association with neurological, ocular and skeletal findings. The presence of vascular malformations in this condition is unusual; nevertheless, vascular malformations have been suggested by many authors to be part of the spectrum of the same disease. Few cases have been published on the association of SFM with lymphatic malformations. This syndrome is categorized as a mosaic RASopathy due to postzygotic mutations in the HRAS, KRAS or NRAS genes. These genes are involved in the RAF-MEK-ERK signalling pathway, which is activated by mutant cells, increasing cellular proliferation. These mutations have been found only in naevus sebaceous cells, and may be also the explanation for many of the associated pathologies. We report a case of an 18-year-old boy diagnosed with SFM syndrome associated with lymphatic malformation in the legs and agenesia of the inguinal lymph nodes. The lymphatic alterations were diagnosed by gammography of the legs. The genetic diagnosis was confirmed by the presence of a KRAS postzygotic mutation in naevus sebaceous cells of a skin specimen. Genetically confirmed cases of mosaic RASopathies should be used to more accurately characterize phenotypic presentations of this syndrome and develop a future therapeutic strategy, such as molecular targeted therapy.

Adipose tissue depot-specific intracellular and extracellular cues contributing to insulin resistance in obese individuals.

Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity-associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine-rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes [endoplasmic reticulum and oxidative stress] in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin-stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot-dependent, pathogenic roles in obesity-associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.