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Abstract In mammals, sexual size dimorphism often reflects the intensity of sexual selection, yet its connection to genomic evolution remains unexplored. Gene family size evolution can reflect shifts in the relative importance of different molecular functions. Here, we investigate the associate between brain development gene repertoire to sexual size dimorphism using 124 mammalian species. We reveal significant changes in gene family size associations with sexual size dimorphism. High levels of dimorphism correlate with an expansion of gene families enriched in olfactory sensory perception and a contraction of gene families associated with brain development functions, many of which exhibited particularly high expression in the human adult brain. These findings suggest a relationship between intense sexual selection and alterations in gene family size. These insights illustrate the complex interplay between sexual dimorphism, gene family size evolution, and their roles in mammalian brain development and function, offering a valuable understanding of mammalian genome evolution.

Abstract The decline of the iconic monarch butterfly (Danaus plexippus) in North America has motivated research on the impacts of land use and land cover (LULC) change and climate variability on monarch habitat and population dynamics. We investigated spring and fall trends in LULC, milkweed and nectar resources over a 20-year period, and ~ 30 years of climate variables in Mexico and Texas, U.S. This region supports spring breeding, and spring and fall migration during the annual life cycle of the monarch. We estimated a − 2.9% decline in milkweed in Texas, but little to no change in Mexico. Fall and spring nectar resources declined

Abstract Over 4,400 large-scale solar photovoltaic (LSPV) facilities operate in the United States as of December 2021, representing more than 60 gigawatts of electric energy capacity. Of these, over 3,900 are ground-mounted LSPV facilities with capacities of 1 megawatt direct current (MWdc) or more. Ground-mounted LSPV installations continue increasing, with more than 400 projects appearing online in 2021 alone; however, a comprehensive, publicly available georectified dataset including spatial footprints of these facilities is lacking. The United States Large-Scale Solar Photovoltaic Database (USPVDB) was developed to fill this gap. Using US Energy Information Administration (EIA) data, locations of 3,699 LSPV facilities were verified using high-resolution aerial imagery, polygons were digitized around panel arrays, and attributes were appended. Quality assurance and control were achieved via team peer review and comparison to other US PV datasets. Data are publicly available via an interactive web application and multiple downloadable formats, including: comma-separated value (CSV), application programming interface (API), and GIS shapefile and GeoJSON.

Summary: “Candidatus Liberibacter spp.” are insect-vectored, fastidious, and vascular-limited phytopathogens. They are the presumptive causal agents of potato zebra chip, tomato vein clearing, and the devastating citrus greening disease worldwide. There is an urgent need to develop new strategies to control them. In this study, we characterized a dual-specificity serine/tyrosine phosphatase (STP) that is well conserved among thirty-three geographically diverse “Candidatus Liberibacter spp.” and strains that infect multiple Solanaceaea and citrus spp. The STP is expressed in infected plant tissues, localized at the plant cytosol and plasma membrane, and interferes with plant cell death responses. We employed an in silico target-based molecular modeling and ligand screen to identify two small molecules with high binding affinity to STP. Efficacy studies demonstrated that the two molecules can inhibit “Candidatus Liberibacter spp.” but not unrelated pathogens and confer plant disease tolerance. The inhibitors and strategies are promising means to control “Candidatus Liberibacter spp.”

Pulmonary metastasectomy has become a well-established procedure for patients with certain types of solid tumors. Patients are usually scheduled for staged lung metastasectomy in case of primary tumor control, the absence of distant non-lung metastases, and when complete resection is achievable. Nodules are removed with precision resection in order to ensure radical resection with minimal margins; this technique permits good oncological results, preserving the surrounding pulmonary parenchyma and causing minimal distortion compared to staplers. When possible, anatomical resections should be avoided since they are not justified by real oncological advantages and, in the majority of cases, sacrifice too much healthy tissue, possibly leading to inoperability in the case of metachronous relapses. Thus, preserving the maximum amount of pulmonary parenchyma is crucial because repeated metastasectomies are possible and frequent, with no theoretical limits to the number of reinterventions. In our multidisciplinary board team, we support the role of pulmonary metastasectomy as a useful curative therapy, with acceptable morbidity and mortality, with indications to be discussed case-by-case.

Abstract Many devices and objects, from microelectronics to microfluidics, consist of parts made from dissimilar materials, such as different polymers, metals or semiconductors. Techniques for joining such hybrid micro-devices, generally, are based on gluing or thermal processes, which all present some drawbacks. For example, these methods are unable to control the size and shape of the bonded area, and present risks of deterioration and contamination of the substrates. Ultrashort laser bonding is a non-contact and flexible technique to precisely join similar and dissimilar materials, used both for joining polymers, and polymers to metallic substrates, but not yet for joining polymers to silicon. We report on direct transmission femtosecond laser bonding of poly(methyl methacrylate) (PMMA) and silicon. The laser process was performed by focusing ultrashort laser pulses at high repetition rate at the interface between the two materials through the PMMA upper layer. The PMMA-Si bond strength was evaluated as a function of different laser processing parameters. A simple, analytical, model was set up and used to determine the temperature of the PMMA during the bonding process. As a proof of concept, the femtosecond-laser bonding of a simple hybrid PMMA-Si microfluidic device has been successfully demonstrated through dynamic leakage tests.

Channeling between enzymes is a uniquely nanoscale phenomenon that can improve multienzymatic reaction rates. Here, the authors demonstrate that multistep enzyme cascades can self-assemble with nanoparticles into nanoclusters that access channeling and improve the underlying catalytic flux by several fold.

Abstract Uncovering the mechanisms underlying the diffusion of vaccine hesitancy is crucial in fighting epidemic spreading. Toward this ambitious goal, we treat vaccine hesitancy as an opinion, whose diffusion in a social group can be shaped over time by the influence of personal beliefs, social pressure, and other exogenous actions, such as pro-vaccine campaigns. We propose a simple mathematical model that, calibrated on survey data, can predict the modification of the pre-existing individual willingness to be vaccinated and estimate the fraction of a population that is expected to adhere to an immunization program. This work paves the way for enabling tools from network control towards the simulation of different intervention plans and the design of more effective targeted pro-vaccine campaigns. Compared to traditional mass media alternatives, these model-based campaigns can exploit the structural properties of social networks to provide a potentially pivotal advantage in epidemic mitigation.

Abstract Haemosporidian parasites are common in birds but are seldom reported in seabirds. The absence of vectors or genetic resistance to infection have been proposed to explain this pattern. However, screening of blood parasites in many seabirds has been done only by visual inspection of blood smears, which can miss low-intensity infections, and molecular detection of blood parasites must be supported by detection in blood smears to confirm the presence of haemosporidians and avoid false positive cases. Here, we tested for the presence of blood parasites of the genera Plasmodium, Haemoproteus and Leucocytozoon, combining inspection of blood smears and PCR-based detection methods in a highly philopatric colony of blue-footed boobies (Sula nebouxii) in the Tropical North Pacific. Our results indicate that adults in this colony are likely free of these blood parasites, probably due to unsuitable conditions for insect vectors in booby breeding sites, although potential genetic resistance of blue-footed boobies to infection deserves examination. Apparent absence of blood parasites in Isla Isabel boobies indirectly adds to the growing evidence of variation in parasite infections among avian host species that coexist locally.

Following the detection of the quarantine bacterium Xylella fastidiosa (Wells et al.) in the Apulia region (southern Italy) and the identification of spittlebugs as the main vector species that contributes to its epidemic spread, monitoring activities have been intensified in an attempt to implement vector control strategies. To date, sweep nets have been the most widely used sampling method to monitor adult spittlebug populations. Field experiments were carried out, during 2018 and 2019, to evaluate the effectiveness of sticky traps in capturing spittlebugs in different woody crops. The attractiveness of different traps was compared: four colored sticky traps (white, red, blue, and yellow), with the yellow sticky traps having three different background patterns (plain yellow, yellow with a black circle pattern, and yellow with a black line pattern). In addition, the efficiency of the yellow sticky traps was evaluated by placing the traps on the ground or hanging them from the canopies in orchards with different spittlebug population densities. Trap catches of Philaenus spumarius (Linnaeus) and Neophilaenus campestris (Fallén) (Hemiptera: Aphrophoridae) were compared with those collected using sweep nets. The two spittlebug species showed a similar response to the colored traps and were mainly attracted to the yellow sticky traps. Captures throughout the adult season indicated that an accurate estimation of the presence and abundance of spittlebugs can be obtained by integrating the two sampling methods. Moreover, sweep nets appeared to be more efficient in collecting adults soon after their emergence, while the use of sticky traps was more efficient in the rest of the adult season when the use of traps can significantly expedite vector monitoring programs.

Abstract In this work, we performed an experimental investigation supported by a theoretical analysis, to improve knowledge on the laser ablation of silicon with THz bursts of femtosecond laser pulses. Laser ablated craters have been created using 200 fs pulses at a wavelength of 1030 nm on silicon samples systematically varying the burst features and comparing to the normal pulse mode (NPM). Using bursts in general allowed reducing the thermal load to the material, however, at the expense of the ablation rate. The higher the number of pulses in the bursts and the lower the intra-burst frequency, the lower is the specific ablation rate. However, bursts at 2 THz led to a higher specific ablation rate compared to NPM, in a narrow window of parameters. Theoretical investigations based on the numerical solution of the density-dependent two temperature model revealed that lower lattice temperatures are reached with more pulses and lower intra-burst frequencies, thus supporting the experimental evidence of the lower thermal load in burst mode (BM). This is ascribed to the weaker transient drop of reflectivity, which suggests that with bursts less energy is transferred from the laser to the material. This also explains the trends of the specific ablation rates. Moreover, we found that two-photon absorption plays a fundamental role during BM processing in the THz frequency range.

The literature on cold-stimulus headache (CSH) is relatively sparse compared to other primary headache disorders and the studies on the pediatric population are very limited. This systematic review aims to analyze the evidence on CSH in children and adolescents focusing on epidemiology, clinical features, pathogenic mechanisms, and treatments. Our review included 25 studies, among which 9 papers include pediatric cases (4 pediatric samples, 5 mixed samples of children and adults). The aim of this work is to highlight the features of CSH in children and adolescents. In children, the prevalence of CSH is higher than in adults and it is not gender-specific. There is a relevant family history for CSH and the comorbidity with migraine is significant. The triggers and clinical features of CSH due to ingesting a cold stimulus in children overlap with those in adults. CSH due to external application of a cold stimulus (or to environmentally low temperatures) is not studied in children and adolescents. We describe in detail a new pediatric case of CSH triggered by low ambient temperatures; to the best of our knowledge, this represents the first description in the literature. In conclusion, CSH in children is probably underestimated and has peculiar features compared to adults; further studies are needed to better understand its clinical features and pathophysiology.

Abstract A particular type of miniature ceramic vessel locally known as “veneneras” is occasionally found during archaeological excavations in the Maya Area. To date, only one study of a collection of such containers successfully identified organic residues through coupled chromatography–mass spectrometry methods. That study identified traces of nicotine likely associated with tobacco. Here we present a more complete picture by analyzing a suite of possible complementary ingredients in tobacco mixtures across a collection of 14 miniature vessels. The collection includes four different vessel forms and allows for the comparison of specimens which had previously formed part of museum exhibitions with recently excavated, untreated containers. Archaeological samples were compared with fresh as well as cured reference materials from two different species of tobacco (Nicotiana tabacum and N. rustica). In addition, we sampled six more plants which are linked to mind-altering practices through Mesoamerican ethnohistoric or ethnographic records. Analyses were conducted using UPLC-MS metabolomics-based analytical techniques, which significantly expand the possible detection of chemical compounds compared to previous biomarker-focused studies. Results include the detection of more than 9000 residual chemical features. We trace, for the first time, the presence of Mexican marigold (Tagetes lucida) in presumptive polydrug mixtures.

Se obtienen tortillas a partir de harina de maíz nixtamalizado, al cual se le adicionaron diferentes proporciones de harina de B. alicastrum (0, 10, 20 y 30% p/p en base seca). Se analizan las tortillas en relación con la composición química, perfil de aminoácidos, compuestos fenólicos, actividad antioxidante y propiedades físicas. La adición de harina de B. alicastrum en tortillas aumentó la actividad antioxidante, el contenido de minerales, fibra soluble, proteína, triptófano, compuestos fenólicos totales y flavonoides totales comparado con la tortilla control. Los resultados sugieren que la adición de harina de B. alicastrum (10 y 20%) a la harina de maíz mejoró el valor nutricional y funcional de tortillas sin afectar su calidad (rolabilidad, grado de inflado y pérdida por cocción).

ObjectiveWhether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.MethodsParticipants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months.ResultsOf 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5).ConclusionsED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

ObjectiveMultiple HIV outbreaks among persons who inject drugs (PWID) have occurred in the US since 2015. Emergency departments (EDs), recognized as essential venues for HIV screening, may play a unique role in identifying undiagnosed HIV among PWID, who frequently present for complications of injection drug use (IDU). Our objective was to describe changes in HIV diagnoses among PWID detected by an ED HIV screening program and estimate the program's contribution to HIV diagnoses among PWID county-wide during the emergence of a regional HIV outbreak.MethodsThis was a retrospective study of electronically queried clinical records from an urban, safety-net ED's HIV screening program and publicly available HIV surveillance data for its surrounding county, Hamilton County, Ohio. Outcomes included the change in number of HIV diagnoses and the ED's contribution to case identification county-wide, overall and for PWID during 2014-2018.ResultsDuring 2014-2018, the annual number of HIV diagnoses made by the ED program increased from 20 to 42 overall, and from 1 to 18 for PWID. We estimated that the ED contributed 18% of HIV diagnoses in the county and 22% of diagnoses among PWID.ConclusionsThe ED program contributed 1 in 5 new HIV diagnoses among PWID county-wide, further illustrating the importance of ED HIV screening programs in identifying undiagnosed HIV infections. In areas experiencing increasing IDU, HIV screening in EDs can provide an early indication of increasing HIV diagnoses among PWID and can substantially contribute to case-finding during an HIV outbreak.

IntroductionType 2 diabetes is an important public health issue, yet adherence to drugs and regular clinical follow-up is still suboptimal. This study aims to evaluate a community pharmacy programme for monitoring and enhancing adherence to prescribed pharmacological therapies and recommended examinations among patients with confirmed diabetes.MethodsThe intervention was conducted in different Italian areas between April 2017 and January 2018. All adult patients who entered a pharmacy with a personal prescription for any antidiabetic drug and agreed to participate, were interviewed. Those found to be non-adherent received counselling from the pharmacists. All patients were invited for a follow-up interview after 3 months.ResultsOverall, 930 patients were enrolled and completed the baseline interview. We found low rates of non-adherence, ranging from 8% to 13% for prescribed pharmacological therapies, and 11-29% for the recommended clinical examinations. Non-adherence to oral therapies was higher among younger and recently diagnosed patients; that to clinical examinations was higher in men, those with an intermediate duration of diabetes and less educated patients. Large geographical differences persisted after the adjustment for individual factors. Only 306 patients (32.9%) returned for the follow-up interview, most of whom were already adherent at baseline.ConclusionsPoor adherence to drugs or clinical examinations is not easy to identify in the usual operating setting of community pharmacies. Furthermore, the majority of patients did not return for follow-up, making it impossible to evaluate the efficacy of the pharmacists' counselling. It might be more effective to plan interventions addressed to specific subgroups of patients or areas.

Global wind energy has expanded 5-fold since 2010 and is predicted to expand another 8–10-fold over the next 30 years. Wakes generated by wind turbines can alter downwind microclimates and potentially downwind vegetation. However, the design of past studies has made it difficult to isolate the impact of wake effects on vegetation from land cover change. We used hourly wind data to model wake and non-wake zones around 17 wind facilities across the U.S. and compared remotely-sensed vegetation greenness in wake and non-wake zones before and after construction. We located sampling sites only in the dominant vegetation type and in areas that were not disturbed before or after construction. We found evidence for wake effects on vegetation greenness at 10 of 17 facilities for portions of, or the entire growing season. Evidence included statistical significance in Before After Control Impact statistical models, differences >3% between expected and observed values of vegetation greenness, and consistent spatial patterns of anomalies in vegetation greenness relative to turbine locations and wind direction. Wakes induced both increases and decreases in vegetation greenness, which may be difficult to predict prior to construction. The magnitude of wake effects depended primarily on precipitation and to a lesser degree aridity. Wake effects did not show trends over time following construction, suggesting the changes impact vegetation greenness within a growing season, but do not accrue over years. Even small changes in vegetation greenness, similar to those found in this study, have been seen to affect higher trophic levels. Given the rapid global growth of wind energy, and the importance of vegetation condition for agriculture, grazing, wildlife, and carbon storage, understanding how wakes from wind turbines impact vegetation is essential to exploit or ameliorate these effects.

Research on plant root-associated microbial communities may help develop more efficient or sustainable crop production methods. Here the authors analyse the citrus rhizosphere microbiome, using both amplicon and deep shotgun metagenomic sequencing of samples collected across six continents.

Greening disease threatens the productivity of citrus crops worldwide yet the pathosystem is poorly understood. Here, Clark et al. show that an effector cloned from the associated bacteria can suppress host plant papain-like cysteine proteases' activity, suggesting its probable role in pathogenesis.

HIV infection causes the progressive depletion of CD4+ T-lymphocytes and profound modifications of T-cell homeostasis, which persist despite virologically-suppressive treatment and have been linked to a worse clinical outcome. Enduring alterations of the gastrointestinal tract may represent the underlying pathogenic mechanisms of these phenomena. Twenty-six HIV-infected subjects were assessed over a 12-month period following the introduction of antiretroviral therapy. 18 uninfected individuals were enrolled as controls. Parameters of peripheral T-cell homeostasis (activation, maturation), gastrointestinal function (microbial translocation, gut inflammation, fecal microbiota composition) and mucosal immunity (CD4+CCR6+CD161+, CD4+CCR9+α4β7+, stem cell memory CD4+/CD8+ T-cells) were assessed. CD4+CCR6+CD161+ cells were depleted in HIV-infected untreated subjects and maintained significantly lower levels compared to controls, despite the introduction of effective antiviral treatment. The frequency of gut-homing CD4+CCR9+α4β7+ cells was also impaired in untreated infection and correlated with the HIV RNA load and CD4+HLADR+CD38+; during therapy, we observed a contraction of this pool in the peripheral blood and the loss of its correlation with antigenic exposure/immune activation. A partial correction of the balance between stem cell memory pools and T-cell homeostasis was registered following treatment. In HIV-infected subjects with moderate immune-suppression, antiretroviral therapy has a marginal impact on mucosal immune populations which feature distinctive kinetics in the periphery, possibly reflecting their diverse recruitment from the blood to the mucosa. The persistent defects in mucosal immunity may fuel peripheral T-cell abnormalities through diverse mechanisms, including the production of IL-17/IL-22, cellular permissiveness to infection and regulation of T-lymphocyte maturation.

El Algoritmo de Recocido Simulado, cristalización simulada o enfriamiento simulado, es un algoritmo de búsqueda metaheurística para problemas de optimización; el objetivo general de este tipo de algoritmos es encontrar una buena aproximación al valor óptimo de una función en un espacio de búsqueda grande. A este valor se lo denomina "óptimo local u óptimo global". El nombre e inspiración viene del proceso de recocido del acero y cerámicas, una técnica que consiste en calentar y luego enfriar lentamente el material para variar sus propiedades físicas. El calor causa que los átomos aumenten su energía y que puedan así desplazarse de sus posiciones iniciales (un mínimo local de energía); el enfriamiento lento les da mayores probabilidades de recristalizar en configuraciones con menor energía que la inicial (mínimo global). El método fue descrito independientemente por Scott Kirkpatrick, C. Daniel Gelatt y Mario P. Vecchi en 1983.

Nearly one-sixth of U.S. river basins are unable to consistently meet societal water demands while also providing sufficient water for the environment. Water scarcity is expected to intensify and spread as populations increase, new water demands emerge, and climate changes. Improving water productivity by meeting realistic benchmarks for all water users could allow U.S. communities to expand economic activity and improve environmental flows. Here we utilize a spatially detailed database of water productivity to set realistic benchmarks for over 400 industries and products. We assess unrealized water savings achievable by each industry in each river basin within the conterminous U.S. by bringing all water users up to industry- and region-specific water productivity benchmarks. Some of the most water stressed areas throughout the U.S. West and South have the greatest potential for water savings, with around half of these water savings obtained by improving water productivity in the production of corn, cotton, and alfalfa. By incorporating benchmark-meeting water savings within a national hydrological model (WaSSI), we demonstrate that depletion of river flows across Western U.S. regions can be reduced on average by 6.2–23.2%, without reducing economic production. Lastly, we employ an environmentally extended input-output model to identify the U.S. industries and locations that can make the biggest impact by working with their suppliers to reduce water use ‘upstream’ in their supply chain. The agriculture and manufacturing sectors have the largest indirect water footprint due to their reliance on water-intensive inputs but these sectors also show the greatest capacity to reduce water consumption throughout their supply chains.

Huanglongbing (HLB) and Phytophthora foot and root rot are diseases that affect citrus production and profitability. The symptoms and physiological changes associated with these diseases are diagnosed through expensive and time-consuming field measurements. Unmanned aerial vehicles (UAVs) using red/green/blue (RGB, true color) imaging, may be an economic alternative to diagnose diseases. A methodology using a UAV with a RGB camera was developed to assess citrus health. The UAV was flown in April 2018 on a grapefruit field infected with HLB and foot rot. Ten trees were selected for each of the following disease classifications: (HLB-, foot rot−), (HLB+, foot rot−), (HLB-, foot rot+) (HLB+, foot rot+). Triangular greenness index (TGI) images were correlated with field measurements such as tree nutritional status, leaf area, SPAD (leaf greenness), foot rot disease severity and HLB. It was found that 61% of the TGI differences could be explained by Na, Fe, foot rot, Ca, and K. This study shows that diseased citrus trees can be monitored using UAVs equipped with RGB cameras, and that TGI can be used to explain subtle differences in tree health caused by multiple diseases.

In wild long-lived animals, analysis of impacts of stressful natal conditions on adult performance has rarely embraced the entire age span, and the possibility that costs are expressed late in life has seldom been examined. Using 26 years of data from 8541 fledglings and 1310 adults of the blue-footed booby (Sula nebouxii), a marine bird that can live up to 23 years, we tested whether experiencing the warm waters and food scarcity associated with El Niño in the natal year reduces recruitment or survival over the adult lifetime. Warm water in the natal year reduced the probability of recruiting; each additional degree (°C) of water temperature meant a reduction of roughly 50% in fledglings' probability of returning to the natal colony as breeders. Warm water in the current year impacted adult survival, with greater effect at the oldest ages than during early adulthood. However, warm water in the natal year did not affect survival at any age over the adult lifespan. A previous study showed that early recruitment and widely spaced breeding allow boobies that experience warm waters in the natal year to achieve normal fledgling production over the first 10 years; our results now show that this reproductive effort incurs no survival penalty, not even late in life. This pattern is additional evidence of buffering against stressful natal conditions via life-history adjustments.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects.

Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer.

Following the introduction of meningococcal serogroup C conjugate vaccine in Italy in 2005, changes in the epidemiology of Invasive Meningococcal Disease (IMD) were expected. The study aims were to describe the epidemiological trend and to characterize the isolates collected during the period 2008/09-2012/13 by multilocus sequence typing (MLST). Data on laboratory confirmed meningococcal diseases from National Surveillance System of IMD were reported.Poisson regression models were used to estimate the incidence rate over time. Serogrouping and MLST were performed following published methods.The incidence rate of laboratory confirmed meningococcal disease decreased from 0.33 per 100,000 population in 2008/09 to 0.25 per 100,000 population in 2012/13. The serogroup B incidence rate was significantly higher (p

Femtosecond laser surface micro-texturing has emerged as a promising technology to enhance the tribological properties of different kinds of electromechanical devices. In this research paper, we have exploited the intrinsic flexibility and micrometric accuracy of femtosecond laser ablation to realize complex micro-structural modifications on the surface of a laboratory prototype of a steel thrust bearing (un-tapered) pad. The Bruggeman Texture Hydrodynamics theory (BTH) is employed for the design of the anisotropic and non-uniform texture maximizing the thrust load of the pad prototype. The preliminary experimental results, reported in this work, show that the non-uniform micro-texture largely affects the friction characteristics of the contact. In particular, in agreement with the BTH predictions, the tribo-system shows friction properties that are strongly sensitive to the direction of the sliding speed, as a consequence of the micro-fluid dynamics which are designed to occur only in a specific sliding direction. We suggest that the joint action of virtual prototyping (BTH lubrication theory) and ultrafast laser micro-prototyping can lead to unconventional and impressive results in terms of enhanced or tailored contact mechanics properties of the generic lubricated tribopair.

Differential gene expression profiling studies have lead to the identification of several disease biomarkers. However, the oncogenic alterations in coding regions can modify the gene functions without affecting their own expression profiles. Moreover, post-translational modifications can modify the activity of the coded protein without altering the expression levels of the coding gene, but eliciting variations to the expression levels of the regulated genes. These considerations motivate the study of the rewiring of networks co-expressed genes as a consequence of the aforementioned alterations in order to complement the informative content of differential expression. We analyzed 339 mRNAomes of five distinct cancer types to find single genes that presented co-expression patterns strongly differentiated between normal and tumor phenotypes. Our analysis of differentially connected genes indicates the loss of connectivity as a common topological trait of cancer networks, and unveils novel candidate cancer genes. Moreover, our integrated approach that combines the differential expression together with the differential connectivity improves the classic enrichment pathway analysis providing novel insights on putative cancer gene biosystems not still fully investigated.

Although often referred to as “the forgotten chamber”, compared with left ventricle (LV), especially in the past years, the left atrium (LA) plays a critical role in the clinical expression and prognosis of patients with heart and cerebrovascular disease, as demonstrated by several studies. Echocardiographers initially focused on early detection of atrial geometrical abnormalities through monodimensional atrial diameter quantification and then bidimensional (2D) areas and volume estimation. Now, together with conventional echocardiographic parameters, new echocardiographic techniques, such as strain Doppler, 2D speckle tracking and three-dimensional (3D) echocardiography, allow assessing early LA dysfunction and they all play a fundamental role to detect early functional remodelling before anatomical alterations occur. LA dysfunction and its important prognostic implications may be detected sooner by LA strain than by volumetric measurements.

Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO) experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability) in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.

BACKGROUND: Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2(-/-) ASM cell proliferation is EGF-dependent. METHODS AND FINDINGS: Effects of EGF on proliferation of TSC2(-/-) ASM cells and TSC2(-/-) ASM cells transfected with TSC2 gene were determined. In contrast to TSC2(-/-) ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2(-/-) ASM cells. Exposure of TSC2(-/-) ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2(-/-) cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2(-/-) ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2(-/-) ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. CONCLUSION: Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC(-/-) ASM cells, and such EGF-dependency is the result of the lack of tuberin.