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Superirradiance events are phenomena caused by cloud edges that enhance the global solar irradiance measured at the surface. On the other hand, extreme superirradiance is characterized by irradiance values higher than the estimated extraterrestrial irradiance. In this sense, the purpose of this work is to understand superirradiance and extreme superirradiance in the Brazilian Northeast and to describe all the aspects identified in the research. Four stations are analyzed: Caicó, Natal, Petrolina and São Luís. The methodology includes data with a 1-minute period and two criteria for event identification: superirradiance and extreme superirradiance. The Spearman’s coefficient is used to correlate the monthly distribution of superradiance with some meteorological variables. As a result, it is observed that superirradiance events can occur throughout the year in the Brazilian Northeast, but extreme superirradiance is more common in the summer months. The duration of both types of events is, in most observations, around 1 min. It is also noted that superirradiance at the São Luís station is positively correlated with precipitation and cloudiness but negatively with insolation. In Natal, superradiance showes a positive correlation with precipitation only. The impacts of superradiance can affect the performance of photovoltaic modules, human and animal health, agriculture, and other activities. [ABSTRACT FROM AUTHOR]

Alzheimer’s Disease (AD) significantly aggravates human dignity and quality of life. While newly approved amyloid immunotherapy has been reported, effective AD drugs remain to be identified. Here, we propose a novel AI-driven drug-repurposing method, DeepDrug, to identify a lead combination of approved drugs to treat AD patients. DeepDrug advances drug-repurposing methodology in four aspects. Firstly, it incorporates expert knowledge to extend candidate targets to include long genes, immunological and aging pathways, and somatic mutation markers that are associated with AD. Secondly, it incorporates a signed directed heterogeneous biomedical graph encompassing a rich set of nodes and edges, and node/edge weighting to capture crucial pathways associated with AD. Thirdly, it encodes the weighted biomedical graph through a Graph Neural Network into a new embedding space to capture the granular relationships across different nodes. Fourthly, it systematically selects the high-order drug combinations via diminishing return-based thresholds. A five-drug lead combination, consisting of Tofacitinib, Niraparib, Baricitinib, Empagliflozin, and Doxercalciferol, has been selected from the top drug candidates based on DeepDrug scores to achieve the maximum synergistic effect. These five drugs target neuroinflammation, mitochondrial dysfunction, and glucose metabolism, which are all related to AD pathology. DeepDrug offers a novel AI-and-big-data, expert-guided mechanism for new drug combination discovery and drug-repurposing across AD and other neuro-degenerative diseases, with immediate clinical applications. [ABSTRACT FROM AUTHOR]

Atomic nuclei serve as prime laboratories for investigations of complex quantum phenomena, where minor nucleon rearrangements cause significant structural changes. 190Pb is the heaviest known neutron-deficient Pb isotope that can exhibit three distinct shapes: prolate, oblate, and spherical, with nearly degenerate excitation energies. Here we report on the combined results from three state-of-the-art measurements to directly observe these deformations in 190Pb. Contrary to earlier interpretations, we associate the collective yrast band as predominantly oblate, while the non-yrast band with higher collectivity follows characteristics of more deformed, predominantly prolate bands. Direct measurement of the E 0 ( 0 2 + → 0 1 + ) transition and γ-e− coincidence relations allowed us to locate and firmly assign the 0 2 + state in the level scheme and to discover a spherical 2 3 + state at 1281(1) keV with B (E 2 ; 2 3 + → 0 1 + ) = 1.2 (3) W.u. These assignments are based purely on observed transition probabilities and monopole strength values, and do not rely on model calculations for their interpretation. Direct measurements reveal that the neutron-deficient isotope 190Pb can adopt three different deformations near the ground state. The present work identifies the collective yrast band as predominantly oblate, the non-yrast band as predominantly prolate, and discovers a candidate spherical 2 3 + state at 1281 keV. [ABSTRACT FROM AUTHOR]

Excited states above the 9 + isomer in the odd-odd N = Z nucleus 66 As were studied by employing the 40 Ca( 28 Si, pn) fusion-evaporation reaction at the Accelerator Laboratory of the University of Jyväskylä, Finland. A key method in this study was the use of conversion electrons emitted in the de-excitation of the isomeric state in 66 As as a tag for prompt γ rays. Several new states have been added to the 66 As level scheme, which was extended up to a tentative spin of 23 ħ . The previously reported even-spin yrast band has been reassigned to have odd spin values. The odd-spin states above the 9 + isomer are compared with shell-model calculations using the jj44b and JUN45 interactions. Additionally, the recoil- β tagging efficiency of the recently developed scintillator detector named Tuike has been determined experimentally for the first time. [ABSTRACT FROM AUTHOR]

Cocaine use disorder (CUD) is a chronic neuropsychiatric disorder estimated to effect 1–3% of the population. Activity-dependent neuroprotective protein (ADNP) is essential for brain development and functioning, shown to be protective in fetal alcohol syndrome and to regulate alcohol consumption in adult mice. The goal of this study was to characterize the role of ADNP, and its active peptide NAP (NAPVSIPQ), which is also known as davunetide (investigational drug) in mediating cocaine-induced neuroadaptations. Real time PCR was used to test levels of Adnp and Adnp2 in the nucleus accumbens (NAc), ventral tegmental area (VTA), and dorsal hippocampus (DH) of cocaine-treated mice (15 mg/kg). Adnp heterozygous (Adnp+/−)and wild-type (Adnp+/−) mice were further tagged with excitatory neuronal membrane-expressing green fluorescent protein (GFP) that allowed for in vivo synaptic quantification. The mice were treated with cocaine (5 injections; 15 mg/kg once every other day) with or without NAP daily injections (0.4 µg/0.1 ml) and sacrificed following the last treatment. We analyzed hippocampal CA1 pyramidal cells from 3D confocal images using the Imaris x64.8.1.2 (Oxford Instruments) software to measure changes in dendritic spine density and morphology. In silico ADNP/NAP/cocaine structural modeling was performed as before. Cocaine decreased Adnp and Adnp2 expression 2 h after injection in the NAc and VTA of male mice, with mRNA levels returning to baseline levels after 24 h. Cocaine further reduced hippocampal spine density, particularly synaptically weaker immature thin and stubby spines, in male Adnp+/+) mice while increasing synaptically stronger mature (mushroom) spines in Adnp+/−) male mice and thin and stubby spines in females. Lastly, we showed that cocaine interacts with ADNP on a zinc finger domain identical to ketamine and adjacent to a NAP-zinc finger interaction site. Our results implicate ADNP in cocaine abuse, further placing the ADNP gene as a key regulator in neuropsychiatric disorders. Ketamine/cocaine and NAP treatment may be interchangeable to some degree, implicating an interaction with adjacent zinc finger motifs on ADNP and suggestive of a potential sex-dependent, non-addictive NAP treatment for CUD. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) is essential for neurodevelopment and de novo mutations in ADNP cause the ADNP syndrome. From brain pathologies point of view, tauopathy has been demonstrated at a young age, implying stunted development coupled with early/accelerated neurodegeneration. Given potential genotype–phenotype differences and age-dependency, we have assessed here a cohort of 15 individuals (1–27-year-old), using 1–3 longitudinal parent (caretaker) interview/s (Vineland 3 questionnaire) over several years. Our results indicated developmental delays, or even developmental arrests, coupled with potential spurts of development at early ages. Severe outcomes correlated with the truncating high impact mutation, in other words, the remaining mutated protein length as well as with the tested individual age, corroborating the hypothesis of developmental delays coupled with accelerated aging. A significant correlation was noted between mutated protein length and communication, implying a high impact of ADNP on communicative skills. Additionally, correlations were discovered between the two previously described epi-genetic signatures in ADNP emphasizing aberrant acquisition of motor behaviors, with truncating mutations around the nuclear localization signal being mostly affected. Finally, all individuals seem to acquire an age equivalent of 1–6 years, requiring disease modification treatment, such as the ADNP-derived drug candidate, NAP (davunetide), which has recently shown efficacy in women suffering from the neurodegenerative disorder, progressive supranuclear palsy (PSP), a late-onset tauopathy. [ABSTRACT FROM AUTHOR]

A complete study of 14 olive cultivars of great economic importance was carried out. These cultivars are Arbequina, Arbosana, Chemlali, Cornicabra, Cornezuelo de Jaén, Empeltre, Frantoio, Hojiblanca, Koroneiki, Manzanilla de Sevilla, Martina, Picual, Sikitita1 and Sikitita 2. All of them are certified by the World Olive Germplasm Bank of Córdoba (Spain). They are predominant cultivars in the olive groves of different locations throughout the Mediterranean basin, and they were subjected to total water deficit for a minimum of 14 days and a maximum of 42 days in the present study. Data such as chlorophyll content, soil moisture and specific leaf area were gathered. Photosynthetic parameters measured at the respective saturation irradiance of each cultivar were also analysed: assimilation rate, transpiration, stomatal conductance, photosynthetic efficiency, photochemical and non-photochemical quenching, photonic flux density, electron transference ratio, efficient use of water and amount of proline and malondialdehyde as indicators of oxidative stress. In addition to the control, two different experimental conditions were analysed: moderate drought, after 14 days of lack of irrigation, and severe drought, after 28–42 days of total absence of irrigation, depending on the tolerance of each cultivar. Based on the results, the cultivars were characterised and divided into four groups according to their drought tolerance: tolerant, moderately tolerant, moderately sensitive and sensitive to drought. This work represents the first contribution of drought tolerance of a considerable number of olive cultivars, with all of them being subjected to the same criteria and experimental conditions for their classification. Key message: Classification of 14 olive cultivars of great economic importance according to their drought tolerance, based on the analysis of numerous physiological, photosynthetic and biochemical parameters. [ABSTRACT FROM AUTHOR]

We investigate the parameter space of the new Littlest Higgs model with T-parity (NLHT) recently introduced to cure some pathologies of the original LHT. The model requires extra fermion content and additional pseudo-Goldstone bosons. While the heavy top quark sector is similar, there are both T-odd and T-even heavy quarks and leptons with masses proportional to just two sets of Yukawa matrices in flavor space, one more than in the LHT. The new scalars are a singlet and real triplet, T-odd, with masses controlled by gauge and Yukawa couplings, independent of the spontaneous symmetry breaking scale f, and hence potentially light. Imposing that no mass exceeds the cutoff scale, applying current lower bounds on vector-like quarks and assuming a simplified model with mass degenerate heavy fermions compatible with the heavy photon as dark matter constituent, we find that f gets constrained within the interval between 2 and 3 TeV, the common Yukawa coupling of heavy leptons gets fixed and the Yukawa coupling of heavy quarks becomes greatly correlated to the top quark Yukawa couplings. The particle spectrum is then bounded from below and above, with the (lightest) heavy photon at about 0.5 TeV, not far from the heavy leptons, the new scalars below 1 TeV, the usual complex scalar triplet close to the heavy weak bosons at about 1.5 to 2.5 TeV, and the heavy quarks and top quark partners between 2 and 5 TeV. The new scalars decay predominantly to a standard and a T-odd lepton and have a width comparable to that of the Higgs. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate natural history of the syndrome, mothers of two ADNP syndrome boys aged 6 and a half and two adults aged 27 years (man and woman) were subjected to Vineland III questionnaire assessing adaptive behavior. The boys were assessed again about 2 years after the first measurements. The skill measures, presented as standard scores (SS) included domains of communication, daily living, socialization, motor skills and a sum of adaptive behavior composite. The age equivalent (AE) and growth scale values (GSV) encompassing 11 subdomains assess the age level at which the subject's raw score is found at a norm sample median and the individual temporal progression, respectively. The norm referenced standard scores age-matched, mean 100 ± 15 of the two children showed the lowest outcome in communication (SS: 20–30). Daily living skills presented SS of 50–60, with a possible potential loss of some activities as the child ages, especially in interpersonal relationships with people outside of the immediate family (boy A). In contrast, in socialization, both children were at the SS of 38, with some positive increase to SS of ~ 45 (interpersonal relations with family members and coping skills, depending on the particular individual), 2 years later. Interestingly, there was an apparent large difference in motor skills (gross and fine) at the young age, with subject B showing a relatively higher level of skills (SS: 70), decreasing to subject A level (SS: 40) 2 years later. Together, the adaptive behavior composite suggested a level of SS: 39–48 with B showing a potential increase (SS: 41–44) and A, a substantial decrease (SS: 48–39), suggesting a strong impact of daily living skills. Adults were at SS: 20, which is the lowest possible score. AE showed minor improvements for subject A and B, with all AE values being below 3 years. GSVs for subject A showed some improvement with age, especially in interpersonal, play and leisure, and gross motor subdomains. GSV for subject B showed minor improvements in the various subdomains. Notably, all subjects showed a percentile rank < 1 compared with age-matched norms except for subject B as to motor domain (2nd percentile) at the age of 6 years. In summary, the results, especially comparing SS and AEs between childhood and adulthood, implied a continuous deterioration of activities compared to the general population, encompassing a slower developmental process coupled to possible neurodegeneration, strongly supporting a great need for disease modifying medicinal procedures. [ABSTRACT FROM AUTHOR]

The β -delayed γ spectroscopy of 81 As has been performed using a purified beam of 81 Ge (9 / 2 +) ground state at the Ion Guide Isotope Separator On-Line facility (IGISOL). The 81 Ge + ions were produced using proton-induced fission of 232 Th and selected with the double Penning trap JYFLTRAP for the post-trap decay spectroscopy measurements. The low-spin (1 / 2 +) isomeric-state ions 81 m Ge + were not observed in the fission products. The intrinsic half-life of the 81 Ge ground state has been determined as T 1 / 2 = 6.4 (2) s , which is significantly shorter than the literature value. A new level scheme of 81 As has been built and is compared to shell-model calculations. [ABSTRACT FROM AUTHOR]

We inspect the Littlest Higgs model with T-parity, based on a global symmetry SU(5) spontaneously broken to SO(5), in order to elucidate the pathologies it presents due to the non-trivial interplay between the gauge invariance associated to the heavy modes and the discrete T-parity symmetry. In particular, the usual Yukawa Lagrangian responsible for providing masses to the heavy 'mirror' fermions is not gauge invariant. This is because it contains an SO(5) quintuplet of right-handed fermions that transforms nonlinearly under SU(5), hence involving in general all SO(5) generators when a gauge transformation is performed and not only those associated to its gauge subgroup. Part of the solution to this problem consists of completing the right-handed fermion quintuplet with T-odd 'mirror partners' and a gauge singlet, what has been previously suggested for other purposes. Furthermore, we find that the singlet must be T-even, the global symmetry group must be enlarged, an additional nonlinear sigma field should be introduced to parametrize the spontaneous symmetry breaking and new extra fermionic degrees of freedom are required to give a mass to all fermions in an economic way while preserving gauge invariance. Finally, we derive the Coleman–Weinberg potential for the Goldstone fields using the background field method. [ABSTRACT FROM AUTHOR]

This study investigates thoroughly whether acute exposure to outdoor PM2.5 concentration, P, modifies the rate of change in the daily number of COVID-19 infections (R) across 18 high infection provincial capitals in China, including Wuhan. A best-fit multiple linear regression model was constructed to model the relationship between P and R, from 1 January to 20 March 2020, after accounting for meteorology, net move-in mobility (NM), time trend (T), co-morbidity (CM), and the time-lag effects. Regression analysis shows that P (β = 0.4309, p < 0.001) is the most significant determinant of R. In addition, T (β = −0.3870, p < 0.001), absolute humidity (AH) (β = 0.2476, p = 0.002), P × AH (β = −0.2237, p < 0.001), and NM (β = 0.1383, p = 0.003) are more significant determinants of R, as compared to GDP per capita (β = 0.1115, p = 0.015) and CM (Asthma) (β = 0.1273, p = 0.005). A matching technique was adopted to demonstrate a possible causal relationship between P and R across 18 provincial capital cities. A 10 µg/m3 increase in P gives a 1.5% increase in R (p < 0.001). Interaction analysis also reveals that P × AH and R are negatively correlated (β = −0.2237, p < 0.001). Given that P exacerbates R, we recommend the installation of air purifiers and improved air ventilation to reduce the effect of P on R. Given the increasing observation that COVID-19 is airborne, measures that reduce P, plus mandatory masking that reduces the risks of COVID-19 associated with viral-particulate transmission, are strongly recommended. Our study is distinguished by the focus on the rate of change instead of the individual cases of COVID-19 when modelling the statistical relationship between R and P in China; causal instead of correlation analysis via the matching analysis, while taking into account the key confounders, and the individual plus the interaction effects of P and AH on R. [ABSTRACT FROM AUTHOR]

Molecular astronomy is a field that is blooming in the era of large observatories such as the Atacama Large Millimeter/Submillimeter Array (ALMA). With modern, sensitive, and high spectral resolution radio telescopes like ALMA and the Square Kilometer Array, the size of the data cubes is rapidly escalating, generating a need for powerful automatic analysis tools. This work introduces MolPred, a pilot study to perform predictions of molecular parameters such as excitation temperature (Tex) and column density (log(N)) from input spectra by the use of neural networks. We used as test cases the spectra of CO, HCO+, SiO and CH3CN between 80 and 400 GHz. Training spectra were generated with MADCUBA, a state-of-the-art spectral analysis tool. Our algorithm was designed to allow the generation of predictions for multiple molecules in parallel. Using neural networks, we can predict the column density and excitation temperature of these molecules with a mean absolute error of 8.5% for CO, 4.1% for HCO+, 1.5% for SiO and 1.6% for CH3CN. The prediction accuracy depends on the noise level, line saturation, and number of transitions. We performed predictions upon real ALMA data. The values predicted by our neural network for this real data differ by 13% from the MADCUBA values on average. Current limitations of our tool include not considering linewidth, source size, multiple velocity components, and line blending. [ABSTRACT FROM AUTHOR]

Encompassing live cell imaging and morphometrics at the microscopical level, we showed here, for the first time, protection of neuronal-like cells by the novel drug candidate, SKIP, against the Parkinson's disease-related neurotoxin, rotenone. Mechanistically, rotenone disrupted microtubule dynamics, which SKIP partially repaired through microtubule end-binding proteins, coupled with increasing neurite branch length. Given the previous association of rotenone toxicity with increased dopaminergic cell death hallmarking Parkinson's disease, we chose an established rat model of 6-hydroxydopamine (6-OHDA) toxicity to initially evaluate SKIP in vivo. SKIP pretreatment showed protection against nigral dopaminergic cell degeneration and improved motor behavior in the forelimb asymmetry test. With Parkinson's disease being a major neurodegenerative disorder, afflicting millions of people globally, and with disease modification challenges, SKIP may hold promise for future therapeutic development. [ABSTRACT FROM AUTHOR]

Lifetime measurements in 178 Pt with excited states de-exciting through γ -ray transitions and internal electron conversions have been performed. Ionic charges were selected by the in-flight mass separator MARA and measured at the focal plane in coincidence with the 4 1 + → 2 1 + 257 keV γ -ray transition detected using the JUROGAM 3 spectrometer. The resulting charge-state distributions were analysed using the differential decay curve method (DDCM) framework to obtain a lifetime value of 430(20) ps for the 2 1 + state. This work builds on a method that combines the charge plunger technique with the DDCM analysis. As an alternative analysis, ions were selected in coincidence with the 178 Pt alpha decay ( E alpha = 5.458 (5) MeV) at the focal plane. Lifetime information was obtained by fitting a two-state Bateman equation to the decay curve with the lifetime of individual states defined by a single quadrupole moment. This yielded a lifetime value of 430(50) ps for the 2 1 + state, and 54(6) ps for the 4 1 + state. An analysis method based around the Bateman equation will become especially important when using the charge plunger method for the cases where utilising coincidences between prompt γ rays and recoils is not feasible. [ABSTRACT FROM AUTHOR]

The activity-dependent neuroprotective protein (ADNP) syndrome is an autistic-like disorder, instigated by mutations in ADNP. This syndrome is characterized by developmental delays, impairments in speech, motor function, abnormal hearing, and intellectual disabilities. In the Adnp-haploinsufficient mouse model, many of these impediments are evident, appearing in a sex-dependent manner. In zebra finch songbird (ZF; Taeniopygia guttata), an animal model used for song/language studies, ADNP mRNA most robust expression is observed in the cerebrum of young males, potentially corroborating with male ZF exclusive singing behavior and developed cerebral song system. Herein, we report a similar sex-dependent ADNP expression profile, with the highest expression in the cerebrum (qRT-PCR) in the brain of another songbird, the domesticated canary (Serinus canaria domestica). Additional analyses for the mRNA transcripts of the ADNP regulator, vasoactive intestinal peptide (VIP), sister gene ADNP2, and speech-related Forkhead box protein P2 (FoxP2) revealed multiple sex and brain region–dependent positive correlations between the genes (including ADNP). Parallel transcript expression patterns for FoxP2 and VIP were observed alongside specific FoxP2 increase in males compared with females as well as VIP/ADNP2 correlations. In spatial view, a sexually independent extensive form of expression was found for ADNP in the canary cerebrum (RNA in situ hybridization). The songbird cerebral mesopallium area stood out as a potentially high-expressing ADNP tissue, further strengthening the association of ADNP with sense integration and auditory memory formation, previously implicated in mouse and human. [ABSTRACT FROM AUTHOR]

In this analysis, the energy spectrum of -rays coincident with one particular transition is generated by requiring that the energy of this gating transition lies in a specific range. Each spectrum corresponds to a particular gating transition, background subtracted, so that the peaks observed in the spectrum arise from -ray transitions in coincidence with that transition. For octupole vibrational nuclei in which the negative-parity states arise from coupling an octupole phonon to the positive-parity states, it is expected that HT ht as the phonon prefers to align with the rotational axis. [Extracted from the article]

The jurogam 3 spectrometer has been constructed for in-beam γ -ray spectroscopy experiments in the Accelerator Laboratory of the University of Jyväskylä, Finland. jurogam 3 consists of germanium-detector modules in a compact geometry surrounding a target to measure γ rays emitted from radioactive nuclei. jurogam 3 can be employed in conjunction with one of two recoil separators, the mara vacuum-mode separator or the ritu gas-filled separator, and other ancillary devices. [ABSTRACT FROM AUTHOR]

Studies point to an increased hereditary risk of cluster headache. HCRTR2 gene rs2653349 and ADH4 gene rs1800759 polymorphisms have been associated with cluster headache susceptibility. Also, GNB3 rs5443 polymorphism, associated with increased signal transduction via GPCRs, seems to influence triptan treatment response. DNA from 114 cluster headache patients and 570 non-related controls, representing a general Southeastern European Caucasian (SEC) population, was extracted from buccal swabs and genotyped using real-time PCR. Gene distribution for the rs2653349 was GG = 79.8%, GA = 18.4%, and AA = 1.8% for patients and GG = 79.1%, GA = 19.1%, and AA = 1.8% for controls. The frequency of the mutated A allele was 11.0% for patients and 11.3% for controls. The frequencies for rs5443 were CC = 44.7%, CT = 44.7%, and TT = 10.5% for patients and CC = 43.9%, CT = 42.6%, and TT = 13.5% for controls. The frequency of the mutated T allele was 32.9% for patients and 34.8% for controls. A 2.7-fold more frequent appearance of the mutated T allele was observed in patients with better triptan treatment response, although not statistically significant. For rs1800759, the frequencies were CC = 36.0%, CA = 43.0%, and AA = 21.0% for patients and CC = 34.0%, CA = 50.2%, and AA = 15.8% for controls. The frequency of the mutated A allele was 42.5% and 40.9% for patients and controls, respectively. The mutated T allele of GNB3 rs5443 polymorphism was more prevalent in patients with better triptan treatment response, indicating a possible trend of association between this polymorphism and triptan treatment response in SEC population. According to our observation, no association of HCRTR2 rs2653349 and ADH4 rs1800759 polymorphisms and cluster headache in SEC population could be documented. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) and its protein snippet NAP (drug candidate CP201) regulate synapse formation and cognitive as well as behavioral functions, in part, through microtubule interaction. Given potential interactions between the microbiome and brain function, we now investigated the potential effects of the ADNP-deficient genotype, mimicking the ADNP syndrome on microbiota composition in the Adnp+/– mouse model. We have discovered a surprising robust sexually dichotomized Adnp genotype effect and correction by NAP (CP201) as follows. Most of the commensal bacterial microbiota tested were affected by the Adnp genotype and corrected by NAP treatment in a male sex-dependent manner. The following list includes all the bacterial groups tested—labeled in bold are male Adnp—genotype increased and corrected (decreased) by NAP. (1) Eubacteriaceae (EubV3), (2) Enterobacteriaceae (Entero), (3) Enterococcus genus (gEncocc), (4) Lactobacillus group (Lacto), (5) Bifidobacterium genus (BIF), (6) Bacteroides/Prevotella species (Bac), (7) Clostridium coccoides group (Coer), (8) Clostridium leptum group (Cluster IV, sgClep), and (9) Mouse intestinal Bacteroides (MIB). No similarities were found between males and females regarding sex- and genotype-dependent microbiota distributions. Furthermore, a female Adnp+/– genotype associated decrease (contrasting male increase) was observed in the Lactobacillus group (Lacto). Significant correlations were discovered between specific bacterial group loads and open-field behavior as well as social recognition behaviors. In summary, we discovered ADNP deficiency associated changes in commensal gut microbiota compositions, a sex-dependent biomarker for the ADNP syndrome and beyond. Strikingly, we discovered rapidly detected NAP (CP201) treatment-dependent biomarkers within the gut microbiota. [ABSTRACT FROM AUTHOR]

We show that the inverse see-saw is the most natural way of implementing neutrino masses in the Littlest Higgs model with T-parity. The three extra quasi-Dirac neutrinos are needed to cancel the quadratically divergent contributions of the mirror leptons to the Higgs mass. If the T-parity of the heavy neutrino singlets is chosen to be even, their contributions to lepton flavor violating transitions are one-loop finite. The most stringent limits on this scenario result from the non-observation of these transitions. Constraints on neutrino mixing imply an upper bound on the mass of the T-odd mirror leptons at the reach of the LHC and/or future colliders. [ABSTRACT FROM AUTHOR]

Α number of genetic variants have been associated with Alzheimer's disease (AD) susceptibility. Sec1 family domain-containing protein 1 (SCFD1) gene polymorphism rs10139154 has recently been implicated in the risk of developing amyotrophic lateral sclerosis (ALS). Similarities in the pathogenetic cascade of both diseases have also been described. The present study was designed to evaluate the possible contribution of SCFD1 rs10139154 to AD. A total of 327 patients with AD and an equal number of healthy controls were included in the study and genotyped for rs10139154. With logistic regression analyses, rs10139154 was examined for the association with the risk of developing AD. In the recessive mode, SCFD1 rs10139154 was associated with a decreased risk of developing AD (odds ratio (OR) (95% confidence interval (CI)) = 0.63 (0.40–0.97), p = 0.036). The current study provides preliminary evidence of the involvement of SCFD1 rs10139154 in the risk of developing AD. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) is essential for embryonic development with ADNP mutations leading to syndromic autism, coupled with intellectual disabilities and motor developmental delays. Here, mining human muscle gene-expression databases, we have investigated the association of ADNP transcripts with muscle aging. We discovered increased ADNP and its paralogue ADNP2 expression in the vastus lateralis muscle of aged compared to young subjects, as well as altered expression of the ADNP and the ADNP2 genes in bicep brachii muscle of elderly people, in a sex-dependent manner. Prolonged exercise resulted in decreased ADNP expression, and increased ADNP2 expression in an age-dependent manner in the vastus lateralis muscle. ADNP expression level was further correlated with 49 genes showing age-dependent changes in muscle transcript expression. A high degree of correlation with ADNP was discovered for 24 genes with the leading gene/protein being NMNAT1 (nicotinamide nucleotide adenylyl transferase 1). Looking at correlations differentiating the young and the old muscles and comparing protein interactions revealed an association of ADNP with the cell division cycle 5-like protein (CDC5L), and an aging-muscle–related interactive pathway in the vastus lateralis. In the bicep brachii, very high correlation was detected with genes associated with immune functions as well as mitochondrial structure and function among others. Taken together, the results suggest a direct association of ADNP with muscle strength and implicate ADNP fortification in the protection against age-associated muscle wasting. [ABSTRACT FROM AUTHOR]

Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally. Respectively, mutations in the human ADNP gene (ADNP syndrome), cause multi-system body dysfunctions with apparent ASD-related traits, commencing as early as childhood. The Adnp haploinsufficient (Adnp+/−) mouse model was researched before in relations to Alzheimer's disease and autism. Adnp+/− mice suffer from deficient social memory, vocal and motor impediments, irregular tooth eruption and short stature, all of which corresponds with reported phenotypes in patients with the ADNP syndrome. Recently, a more elaborated description of the ADNP syndrome was published, presenting impediments such as hearing disabilities in > 10% of the studied children. Irregular auditory brainstem response (ABR) has been connected to ASD-related cases and has been suggested as a potential hallmark for autism, allowing diagnosis of ASD risk and early intervention. Herein, we present detriment hearing in the Adnp+/− mice with atypical ABR and significant protein expression irregularities that coincides with ASD and hearing loss studies in the brain. [ABSTRACT FROM AUTHOR]

A rise in social work programs has led to increased needs for quality field placements. Social workers are expected to occupy educator roles in addition to increasing clinical demands and responsibilities within their work settings. In response to this demand, rotational models of field placements have been introduced. This qualitative study Examined recent trends and perspectives of acute-care hospital social workers engaged in rotational models of supervision. Using focus group data and qualitative data analysis, results indicated that the model has grown in popularity over the past decade, with increasing use for Year 2 MSW students. Social workers appreciate the manageable duration of the model, collaboration with fellow supervisors, and report various benefits to students from this model. [ABSTRACT FROM AUTHOR]

Manganese (Mn)-containing dithiocarbamates such as Mancozeb (MZ) have been shown to induce oxidative stress-related toxicity in rodents and humans. However, little is known about the neurotoxic effects induced by MZ in fish. In this study, carp (Cyprinus carpio) were exposed to non-lethal waterborne concentrations of MZ, and oxidative stress parameters as well as metal accumulation in fish brains were evaluated. The experimental groups were as follows: control, MZ 5 mg/L, and MZ 10 mg/L. Fish were exposed for 7 days, and then brain was removed and prepared for subsequent analysis of antioxidant enzymes, reactive oxygen species (ROS), and expression of Nrf2 and phosphoNrf2. In parallel, manganese (Mn) levels were evaluated in blood and brain tissues. Mn levels were significantly increased in blood and brain of MZ-exposed carps. In addition, a concentration-dependent increase (p < 0.05) in ROS levels was observed in parallel to increments (p < 0.05) in the activity of major antioxidant enzymes, such as GPx, GR, and GST. On the other hand, significant decreases (p < 0.05) in CAT and SOD activities were observed. The expression of total and phosphorylated forms of Nrf2 was significantly (p < 0.05) upregulated in the brain of carps exposed to Mz when compared to the control, indicating an activation of the Nrf2 antioxidant pathway. Our study showed for the first time the activation of the Nrf2/ARE pathway and bioaccumulation of Mn induced by MZ exposure in fish species, highlighting important mechanisms of action and its toxicological impacts to aquatic organisms. [ABSTRACT FROM AUTHOR]

A critical step in patient care path is diagnosis. The demand for advanced imaging tests, such as computerized axial tomography, magnetic resonance imaging and positron emission tomography (PET), increased dramatically in the past 15 years. Since imaging equipment remains relatively expensive, in order to fit the demand, the imaging resources must be managed effectively while ensuring required quality of service. In PET, a radiopharmaceutical (radioactive substance) is injected to patients prior to their scans. The time between substance injection and scan (standby or uptake time) is rigid. This constraint makes the patient appointment scheduling more challenging, because if at the end of the expected uptake time the scanner is not available, the quality of the scan is jeopardized (due to short half-life duration of the substance). The availability of the scanner is a consequence of prior scans’ appointments and durations. The aim of this work is to develop an approach for appointment scheduling in a system with one scanner, given a sequence of patients and rigid uptake time, in order to minimize the length of day while satisfying a minimal pre-determined quality of service. In order to solve this stochastic problem, we formulate its equivalent deterministic problem, based on simulated data, as a mixed-integer linear programming. To overcome the dimensionality limitations, we develop a simulation-based sequential algorithm that solves the problem in a reasonable time. We found that a fixed slot per scan policy, as a benchmark, is inferior to our method, especially in achieving stable and fair quality of service for patients. [ABSTRACT FROM AUTHOR]

This short editorial provides our point of view of the first EURO TAU meeting focusing on tau diagnostics and clinical studies. We cover postmortem analyses toward the identification of new biomarkers, tau imaging as a diagnostic biomarker, cerebrospinal fluid (CSF) sampling with emphasis on tau fragments, blood tests and genetic evaluations for sporadic cases, treatment aspects, drug development and points for future developments toward disease modification of devastating tauopathies. [ABSTRACT FROM AUTHOR]