Simultaneous Loss Research Articles

Yin Yang 1 controls cerebellar astrocyte maturation.

Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain mature astrocytes in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.

Response to Bagan, Danylevska, and Ilyukhina: The drones of Thanatos

ABSTRACT Our Ukrainian colleagues write from the epicenter of a war that ripples outward, touching us too as distant neighbors in a global economy and community. This response summarizes their experience and focuses on a significant pattern that stands out amongst the many ordeals: the impact of multiple, simultaneous, and cumulative losses which combine, becoming a “complex-context,” a disturbing addition to stress on relational connections. The implications of this are explored along with the way self-experience is affected. These therapists offer poignant glimpses into the difficulties of being a “Relational Home” to patients when both are thrown into a collective tragedy. We in the US, may wish to respond in kinship, in turn becoming their Relational Homes, but we must then in addition to understanding the existential phenomenology that is integral to all human lives, find analogs relevant to their gritty experience: uncertainty about basic survival, ruination of home and other symbolic objects, brutal intrusions including the news of atrocities, and the terrifying destabilization of familiar selfhood. Using an intersubjective-systems theory perspective on working with trauma I offer a possible way that we in the USA can derive analogs from recent American experience.

Chlamydomonas reinhardtii-A Reference Microorganism for Eukaryotic Molybdenum Metabolism.

Molybdenum (Mo) is vital for the activity of a small but essential group of enzymes called molybdoenzymes. So far, specifically five molybdoenzymes have been discovered in eukaryotes: nitrate reductase, sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and mARC. In order to become biologically active, Mo must be chelated to a pterin, forming the so-called Mo cofactor (Moco). Deficiency or mutation in any of the genes involved in Moco biosynthesis results in the simultaneous loss of activity of all molybdoenzymes, fully or partially preventing the normal development of the affected organism. To prevent this, the different mechanisms involved in Mo homeostasis must be finely regulated. Chlamydomonas reinhardtii is a unicellular, photosynthetic, eukaryotic microalga that has produced fundamental advances in key steps of Mo homeostasis over the last 30 years, which have been extrapolated to higher organisms, both plants and animals. These advances include the identification of the first two molybdate transporters in eukaryotes (MOT1 and MOT2), the characterization of key genes in Moco biosynthesis, the identification of the first enzyme that protects and transfers Moco (MCP1), the first characterization of mARC in plants, and the discovery of the crucial role of the nitrate reductase-mARC complex in plant nitric oxide production. This review aims to provide a comprehensive summary of the progress achieved in using C. reinhardtii as a model organism in Mo homeostasis and to propose how this microalga can continue improving with the advancements in this field in the future.

Polarimetric parity-time symmetry fiber laser with switchable and tunable orthogonal single-polarization narrow-linewidth output

Parity-time (PT) symmetry has garnered significant attention in the field of photonics owing to its remarkable properties. High-performance lasers, which require simultaneous gain and loss, serve as an ideal platform for harnessing the exceptional properties of PT symmetry. In this study, we present and experimentally verify a polarimetric PT-symmetry fiber laser that uses a polarization-maintaining fiber Bragg grating (PM-FBG). This design allows for tunable, switchable dual-wavelength operation with narrow linewidth and orthogonal single-polarization characteristics. By converting two equal-length yet distinct polarization states into two spatial subspaces sharing a common wavelength space, we can achieve PT symmetry. Regulating the polarization controllers (PCs) enables interconversion between PT-symmetry phases. During the PT-symmetric phase (or PT exact phase), a dual-wavelength laser is realized with wavelength fluctuations below 0.098 nm and power fluctuations below 2.175 dB. At this stage, light propagates through both ordinary and extraordinary wavelength-spaces. During the PT-broken phase, one waveguide has a net gain and the other incurs a net loss, leading to a single longitudinal mode (SLM) laser output. The wavelength and power fluctuations of left-wavelength λ1 and right-wavelength λ2 remain below 0.002 nm and 0.770 dB over a 20-minute period, during single-wavelength operation. By adjusting the axial strain on the PM-FBG, the laser output can be tuned within the wavelength range of 1549.754 nm to 1551.690 nm, while maintaining a linewidth variation of less than 0.130 kHz. As the wavelength is adjusted, the azimuth sum of λ1 and λ2 consistently remains close to 90 degrees, accompanied by degrees of polarizations exceeding 99%.

Actively tunable graphene ribbon based multi-band THz polarizer with a high extinction ratio

An electrically tunable surface plasmon resonance based graphene ribbon (GR) terahertz (THz) polarizer with an adjustable operating frequency, high extinction ratio, and low insertion loss is reported here, and is simple and fabrication feasible. The proposed metasurface structure comprises a periodic array of graphene ribbons deposited on a quartz–silicon substrate. The operating frequency of the GR-polarizer can be tuned by varying the gap between GRs, GR pitch, GR width, and Fermi level in graphene. Beyond the available graphene-based polarizers, the proposed device exhibits a high extinction ratio (ER) of up to 75 dB with simultaneous insertion loss of ∼1.5dB at the optimized frequency of 1.69 THz. In addition, an average ER of ∼30dB with insertion loss of ∼2dB in the broad frequency range of 0.8–2.5 THz is demonstrated. Such metastructure polarizing devices, enriched with the nontrivial functionalities of graphene, would open up a fertile platform for designing a range of integrated photonic components for useful applications in THz optoelectronics, biomedical engineering, and microfluidics.

Dehydration of Niclosamide Monohydrate Polymorphs: Different Mechanistic Pathways to the Same Product.

Many active pharmaceutical ingredients (APIs) can crystallize as hydrates or anhydrates, the relative stability of which depends on their internal structures as well as the external environment. Hydrates may dehydrate unexpectedly or intentionally, though the molecular-level mechanisms by which such transformations occur are difficult to predict a priori. Niclosamide is an anthelmintic drug on the World Health Organization's "List of Essential Medicines" that crystallizes in two monohydrate forms: HA and HB. Through complementary time-resolved synchrotron powder X-ray diffraction and thermogravimetric kinetic studies, we demonstrate that the two monohydrates dehydrate via distinctly different solid state pathways yet yield the same final anhydrate phase. Water loss from HA via diffusion yields an isomorphous desolvate intermediate which can rearrange to at least two different polymorphs, only one of which exhibits long-term stability. In contrast, dehydration of HB proceeds via a surface nucleation process where simultaneous water loss and product formation occur with no detectable crystalline intermediates. Comparative analysis of the two systems serves to highlight the complex relationship between lattice structure and solid state dehydration processes.

Bars and boxy/peanut bulges in thin and thick discs

The Milky Way and a majority of external galaxies possess a thick disc. However, the dynamical role of the (geometrically) thick disc in the bar formation and evolution is not fully understood. Here, we investigate the effect of thick discs in the formation and evolution of bars by means of a suite of N-body models of (kinematically cold) thin and (kinematically hot) thick discs. We systematically varied the mass fraction of the thick disc, the thin-to-thick disc scale length ratio, and the thick disc scale height to examine the bar formation under diverse dynamical scenarios. Bars form almost always in our models, even in the presence of a massive thick disc. The part of the bar that consists of the thick disc closely follows the overall growth and temporal evolution of the part of the bar that consists of the thin disc, but the part of the bar in the thick disc is weaker than the part of the bar in the thin disc. The formation of stronger bars is associated with a simultaneous greater loss of angular momentum and a more intense radial heating. In addition, we demonstrate a preferential loss of angular momentum and a preferential radial heating of disc stars in the azimuthal direction within the extent of the bar in both thin and thick disc stars. For purely thick-disc models (without any thin disc), the bar formation critically depends on the disc scale length and scale height. A larger scale length and/or a larger vertical scale height delays the bar formation time and/or suppresses the bar formation almost completely in thick-disc-only models. We find that the Ostriker-Peeble criterion predicts the bar instability scenarios in our models better than the Efstathiou-Lake-Negroponte criterion.

Investigation of synthetic lethality gene pairs in the DNA damage response pathway in response to immunotherapy in pan-cancer.

2567 Background: The concept of synthetic lethality (SL) refers to the phenomenon where the simultaneous loss of function of two genes leads to cell death, while the loss of function of either gene alone has no effect. PARP inhibitors target poly ADP ribose polymerase (PARP) enzymes, which are involved in DNA repair, are the successful cases of utilizing synthetic lethality-based therapy to treat cancers with DNA damage response (DDR) deficiency. The prognosis for cancer patients already has a combination of synthetic lethal mutations especially in DDR pathway can vary and it is not yet fully understood how these mutations may impact the response to immunotherapy. Methods: SL gene combinations in the DDR pathway were screened out from SynLethDB database (http://histone.sce.ntu.edu.sg/SynLethDB/). The immunotherapy cohort (Samstein 2019, n=1661) and non-immunotherapy cohort (Zehir 2017, n=10336) with solid tumor were used to Kaplan-Meier analyze the correlation between SL gene combinations and prognosis. TMB scores were compared between DDR co-mutation group and non DDR co-mutation group. For investigating the associations between immune infiltrates and genetic features, TIMER 2.0 database ( http://timer.cistrome.org/ ) was conducted to estimation of immune infiltration levels on DDR mutation genes in pan-cancer. Results: 430 pairs of DDR mutation combinations were used to subgroup stratification, the DDR co-mutation group was associated with worse prognosis in non-immunotherapy cohort (HR=1.305, p<0.0001) but better in immunotherapy cohort (HR=0.741,p<0.0061). Interestingly, the TMB score in the DDR co-mutation group was significantly higher than non DDR co-mutation group (mean 50.03 vs 8.868, p<0.0001) in immunotherapy cohort. The high-frequency mutation combinations (>10%) were ATM-POLE(14.40%), ATM-ATR (13.60%), ATR-BRCA2 (13.60%), ATM-BRCA2 (12.00%) and BRCA2-RECQL4 (10.40%), respectively. Comparing common immune component with statistically significant under different DDR mutant genes, the ATM-POLE co-mutation tumor tended to have more CD4+ T cell infiltration while the ATM-ATR co-mutation tumor appeared to have more myeloid dendritic cell infiltration. Conclusions: The combinations of DDR SL mutation tumor might result to worse prognosis whereas these patients might benefit from immunotherapy. Our results will help to shed light on the complex interplay for the combinations of SL mutation in DDR pathway between cancer cells and the immune system and provide new insights into the development of effective cancer treatments.

Hollow Psychography: Toward Simultaneous 4D Scanning Transmission Electron Microscopy and Electron Energy Loss Spectroscopy.

With the recent development of high-acquisition-speed pixelated detectors, 4D scanning transmission electron microscopy (4D-STEM) is becoming routinely available in high-resolution electron microscopy. 4D-STEM acts as a "universal" method that provides local information on materials that is challenging to extract from bulk techniques. It extends conventional STEM imaging to include super-resolution techniques and to provide quantitative phase-based information, such as differential phase contrast, psychography, or Bloch wave phase retrieval. However, an important missing factor is the chemical and bonding information provided by electron energy loss spectroscopy (EELS). 4D-STEM and EELS cannot currently be acquired simultaneously due to the overlapping geometry of the detectors. Here, the feasibility of modifying the detector geometry to overcome this challenge for bulk specimens is demonstrated, and the use of a partial or defective detector for ptycholgaphic structural imaging is explored. Results show that structural information beyond the diffraction-limit and chemical information from the material can be extracted together, resulting in simultaneous multi-modal measurements, adding the additional dimensions of spectral information to 4D datasets.

Spatiotemporal Patterns in Land Use/Land Cover Observed by Fusion of Multi-Source Fine-Resolution Data in West Africa

Land Use/Land Cover (LULC) change is a major global concern and a topic of scientific debate. In West Africa, the key trend among the changes of the past few years is the loss of natural vegetation related to changes in different LULC categories, e.g., water bodies, wetland, and bare soil. However, not all detected changes in these LULC categories are relevant for LULC change management intervention in a resource-constrained continent, as a massive change in the dominant LULC types may be due to errors in the LULC maps. Previous LULC change analysis detected large discrepancies in the existing LULC maps in Africa. Here, we applied an open and synergistic framework to update and improve the existing LULC maps for West Africa at five-year intervals from 1990 to 2020—updating them to a finer spatial resolution of 30 m. Next, we detected spatial–temporal patterns in past and present LULC changes with the intensity analysis framework, focusing on the following periods: 1990–2000, 2000–2010, and 2010–2020. A faster annual rate of overall transition was detected in 1990–2000 and 2010–2020 than in 2000–2010. We observed consistent increases in shrubland and grassland in all of the periods, which confirms the observed re-greening of rangeland in West Africa. By contrast, forestland areas experienced consistent decreases over the entire period, indicating deforestation and degradation. We observed a net loss for cropland in the drought period and net gains in the subsequent periods. The settlement category also gained actively in all periods. Net losses of wetland and bare land categories were also observed in all of the periods. We observed net gains in water bodies in the 1990–2000 period and net losses in the 2010–2020 period. We highlighted the active forestland losses as systematic and issued a clarion call for an intervention. The simultaneous active gross loss and gain intensity of cropland raises food security concerns and should act as an early warning sign to policy makers that the food security of marginal geographic locations is under threat, despite the massive expansion of cropland observed in this study area. Instead of focusing on the dynamics of all the LULC categories that may be irrelevant, the intensity analysis framework was vital in identifying the settlement category relevant for LULC change management intervention in West Africa, as well as a cost-effective LULC change management approach.

Characteristics and prognostic analysis of simultaneous bilateral sudden sensorineural hearing loss.

To evaluate the clinical characteristics of simultaneous bilateral sudden sensorineural hearing loss (Si-BSSNHL) as well as its prognostic factors. Patients with Si-BSSNHL who were admitted to the Department of Otology Medicine between December 2018 and December 2021 were enrolled in the case group. Propensity score matching (PSM) for sex and age was used to select the control group, which included people who had unilateral sudden sensorineural hearing loss (USSNHL) during the same time period. Hearing recovery, audiological examinations, vestibular function assessments, laboratory tests, and demographic and clinical manifestations were analyzed for intergroup comparisons. Binary logistic regressions were used for both univariate and multivariate analyses of Si-BSSNHL prognostic factors. Before PSM, the Si-BSSNHL and USSNHL groups differed significantly (p < 0.05) in terms of time from onset to treatment, initial pure-tone average (PTA), final PTA, hearing gain, audiogram curve type, proportion of tinnitus, high-density lipoprotein level, homocysteine level, and effective rate. After PSM, significant differences were also observed in time from onset to treatment, initial PTA, final PTA, hearing gain, total and indirect bilirubin levels, homocysteine level, and effective rate between the two groups (p < 0.05). There was a significant difference in the classification of therapeutic effects between the two groups (p < 0.001). For prognostic analysis, the audiogram curve type was significantly different between the effective group and the ineffective groups of Si-BSSNHL (p = 0.01), in which the sloping type was an independent risk factor for the prognosis of the right ear in Si-SSNHL (95% confidence interval, 0.006-0.549, p = 0.013). Patients with Si-BSSNHL had mild deafness, elevated total and indirect bilirubin and homocysteine levels, and poorer prognosis than those with USSNHL. Audiogram curve type was linked to the therapeutic effect of Si-BSSNHL, and the sloping type was an independent risk factor for a poor prognosis in the right ear of Si-SSNHL.

Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.

The structure of DNA replication forks is preserved by TIMELESS (TIM) in the fork protection complex (FPC) to support seamless fork progression. While the scaffolding role of the FPC to couple the replisome activity is much appreciated, the detailed mechanism whereby inherent replication fork damage is sensed and counteracted during DNA replication remains largely elusive. Here, we implemented an auxin-based degron system that rapidly triggers inducible proteolysis of TIM as a source of endogenous DNA replication stress and replisome dysfunction to dissect the signaling events that unfold at stalled forks. We demonstrate that acute TIM degradation activates the ATR-CHK1 checkpoint, whose inhibition culminates in replication catastrophe by single-stranded DNA accumulation and RPA exhaustion. Mechanistically, unrestrained replisome uncoupling, excessive origin firing, and aberrant reversed fork processing account for the synergistic fork instability. Simultaneous TIM loss and ATR inactivation triggers DNA-PK-dependent CHK1 activation, which is unexpectedly necessary for promoting fork breakage by MRE11 and catastrophic cell death. We propose that acute replisome dysfunction results in a hyper-dependency on ATR to activate local and global fork stabilization mechanisms to counteract irreversible fork collapse. Our study identifies TIM as a point of replication vulnerability in cancer that can be exploited with ATR inhibitors.

Cumulative effects on habitat networks: How greedy should we be?

Connectivity conservation and restoration are key strategies to preserve biodiversity under the pressure of habitat loss and fragmentation. Numerous quantitative approaches have been developed to help conservation practitioners take the most effective and cost-efficient actions to conserve, restore or create habitat patches or corridors that preserve or enhance landscape connectivity. This problem is often solved by ranking habitat patches (or corridors) with suboptimal algorithms that do not account for the cumulative effects that may occur in the case of simultaneous or sequential losses (or enhancements) of multiple habitat patches. Accounting for these cumulative effects is one of the current challenges for connectivity conservation. Here, we quantify these cumulative effects and explore the trade-off between solution quality and computational time when optimizing the selection of conservation/restoration actions that maximize landscape connectivity under a budget constraint; connectivity is here measured by the frequently-used Equivalent Connected Area. We compare the solutions obtained with a new optimization pipeline with solutions obtained with four simpler algorithms used in most connectivity conservation studies. Comparison is performed for four case studies covering a wide range of possible applications for conservation practitioners. We show that the simpler algorithms can provide suboptimal solutions, when conservation/restoration actions have a strong impact on least-cost paths between the habitat patches, and that optimal resolution should be considered whenever possible.

Medaka (Oryzias latipes) Olpax6.2 acquires maternal inheritance and germ cells expression, but functionally degenerate in the eye

Gene duplication provides raw material for the evolution of genetic and phenotypic complexity. It has remained a long-standing mystery how duplicated genes evolve into new genes by neofunctionalization via the acquisition of new expression and/or activity and simultaneous loss of the old expression and activity. Fishes have many gene duplicates from whole genome duplication, making them excellent for studying the evolution of gene duplicates. In the fish medaka (Oryzias latipes), an ancestral pax6 gene has given rise to Olpax6.1 and Olpax6.2. Here we report that medaka Olpax6.2 is evolving towards neofunctionalization. A chromosomal syntenic analysis indicated that Olpax6.1 and Olpax6.2 are structurally co-homologous to the single pax6 in other organisms. Interestingly, Olpax6.2 maintains all conserved coding exons but loses the non-coding exons of Olpax6.1, and has 4 promoters versus 8 in Olpax6.1. RT-PCR revealed that Olpax6.2 maintains expression in the brain eye, pancreas as Olpax6.1. Surprisingly, Olpax6.2 also exhibits maternal inheritance and gonadal expression by RT-PCR, in situ hybridization and RNA transcriptome analysis. The expression and distribution of Olpax6.2 is not different from Olpax6.1 in the adult brain, eye and pancreas, but exhibited overlapping and distinct expression in early embryogenesis. We show that ovarian Olpax6.2 expression occurs in female germ cells. Olpax6.2 knockout shows no obvious defect in eye development, while Olpax6.1 F0 mutant have severe defects in eye development. Thus, Olpax6.2 acquires maternal inheritance and germ cell expression, but functionally degenerates in the eye, making this gene as an excellent model to study the neofunctionalization of duplicated genes.

Increase of Simultaneous Soybean Failures Due To Climate Change

AbstractWhile soybeans are among the most consumed crops in the world, most of its production lies in the US, Brazil, and Argentina. The concentration of soybean growing regions in the Americas renders the supply chain vulnerable to regional disruptions. In 2012, anomalous hot and dry conditions occurring simultaneously in these regions led to low soybean yields, which drove global soybean prices to all‐time records. In this study, we explore climate change impacts on simultaneous extreme crop failures as the one from 2012. We develop a hybrid model, coupling a process‐based crop model with a machine learning model, to improve the simulation of soybean production. We assess the frequency and magnitude of events with similar or higher impacts than 2012 under different future scenarios, evaluating anomalies both with respect to present day and future conditions to disentangle the impacts of (changing) climate variability from the long‐term mean trends. We find long‐term trends in mean climate increase the frequency of 2012 analogs by 11–16 times and the magnitude by 4–15% compared to changes in climate variability only depending on the global climate scenario. Conversely, anomalies like the 2012 event due to changes in climate variability show an increase in frequency in each country individually, but not simultaneously across the Americas. We deduce that adaptation of the crop production practice to the long‐term mean trends of climate change may considerably reduce the future risk of simultaneous soybean losses across the Americas.

Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas

Chordomas are rare bone tumors arising along the spine. Due to high resistance towards chemotherapy, surgical resection-often followed by radiation therapy-is currently the gold standard of treatment. So far, targeted systemic therapies have not been approved. The most frequent molecular alterations include the loss of PTEN and CDKN2A (encoding p16), being associated with poor prognoses in chordoma patients. Specific inhibitors of the PI3K/AKT/mTOR pathway as well as CDK4/6 have shown antitumor activity in preclinical studies and have recently been under investigation in phase II clinical trials; however, the clinical impacts and therapeutic consequences of concomitant PTEN and p16 deficiency have not yet been investigated in chordomas. In a cohort of 43 chordoma patients, 16% of the cases were immunohistochemically negative for both markers. The simultaneous loss of PTEN and p16 was associated with a higher KI-67 index, a tendency to metastasize, and significantly shorter overall survival. Additionally, 30% of chordoma cell lines (n = 19) were PTEN-/p16-negative. Treating these chordoma cells with palbociclib (CDK4/6 inhibitor), rapamycin (mTOR inhibitor) or the pan-PI3K inhibitor buparlisib significantly reduced cell viability. Synergistic effects were observed when combining palbociclib with rapamycin. In conclusion, we show that patients with PTEN-/p16-negative chordomas have poor prognoses and provide strong preclinical evidence that these patients might benefit from a Palbociclib/rapamycin combination treatment.

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry.

The activation of cysteine proteases, known as caspases, remains an important process in multiple forms of cell death. Caspases are critical initiators and executioners of apoptosis, the most studied form of programmed cell death. Apoptosis occurs during developmental processes and is a necessary event in tissue homeostasis. Pyroptosis is another form of cell death that utilizes caspases and is a critical process in activating the immune system through the activation of the inflammasome, which results in the release of members of the interleukin-1 (IL-1) family. To assess caspase activity, target substrates can be assessed. However, sensitivity can be an issue when examining single cells or low-level activity. We demonstrate how a fluorogenic substrate can be used with a population-based assay or single-cell assay by flow cytometry. With proper controls, different amino acid sequences can be used to identify which caspases are active. Using these assays, the simultaneous loss of the inhibitors of apoptosis proteins upon tumor necrosis factor (TNF) stimulation has been identified, which primarily induces apoptosis in macrophages rather than other forms of cell death.

Netrin-1 regulates the balance of synaptic glutamate signaling in the adult ventral tegmental area.

The axonal guidance cue netrin-1 serves a critical role in neural circuit development by promoting growth cone motility, axonal branching, and synaptogenesis. Within the adult mouse brain, expression of the gene encoding (Ntn1) is highly enriched in the ventral midbrain where it is expressed in both GABAergic and dopaminergic neurons, but its function in these cell types in the adult system remains largely unknown. To address this, we performed viral-mediated, cell-type specific CRISPR-Cas9 mutagenesis of Ntn1 in the ventral tegmental area (VTA) of adult mice. Ntn1 loss-of-function in either cell type resulted in a significant reduction in excitatory postsynaptic connectivity. In dopamine neurons, the reduced excitatory tone had a minimal phenotypic behavioral outcome; however, reduced glutamatergic tone on VTA GABA neurons induced behaviors associated with a hyperdopaminergic phenotype. Simultaneous loss of Ntn1 function in both cell types largely rescued the phenotype observed in the GABA-only mutagenesis. These findings demonstrate an important role for Ntn1 in maintaining excitatory connectivity in the adult midbrain and that a balance in this connectivity within two of the major cell types of the VTA is critical for the proper functioning of the mesolimbic system.

Modern blepharoplasty: From bench to bedside.

The demand for procedures aiming to rejuvenate the upper third part of the face and the periocular region has increased in the past several years. Blepharoplasty is one of the most frequently performed procedures worldwide to date. Surgery is currently the first choice in order to achieve permanent and effective results; however, it is burdened by potential surgical complications feared by patients. There is an increasing trend in individuals to request less invasive, non-surgical, effective, and safe procedures for eyelid treatment. The aim of this minireview is to present a brief overview of non-surgical blepharoplasty techniques that have been reported in the literature in the past 10 years. Numerous modern techniques that provide a rejuvenation of the entire area have been described. Numerous less invasive methods have been proposed in the current literature and in modern-day routine clinical settings. Dermal fillers are a commonly chosen option for providing enhanced aesthetic results, especially considering that volume loss can be one of the main underlying causes of facial and periorbital aging. Deoxycholic acid use may be considered when the problem is represented by periorbital excess fat deposits. The simultaneous excess and loss of elasticity of the skin can be assessed with techniques such as lasers and plasma exeresis. Furthermore, techniques such as platelet-rich plasma injections and the insertion of twisted polydioxanone threads are emerging as viable methods to rejuvenate the periorbital region.

TiO2 nanoparticle enhanced high temperature proton conductivity in hyperbranched sulfonated polyarylene aliphatic ketones for proton exchange membrane fuel cell applications

AbstractA new hyperbranched sulfonated poly(arylene aliphatic ketones) (HB‐SPAAK) has been synthesized and loaded with titania nanoparticles to obtain HB‐SPAAK/TiO2 nanocomposites for thermally stable proton‐conducting electrolyte membrane fuel cell (PEMFC) applications. The synthesis of HB‐SPAAKs was carried out through the polycondensation reaction of different aliphatic and aromatic acids with simultaneous loss of H2O, trifluromethane sulfonic acid used as catalyst. The long chain hyperbranched polymers and TiO2‐loaded nanocomposites were characterized by FT‐IR, 1H‐NMR, SEM and HR‐TEM. Proton conductivity (PC), swelling ratio, water uptake and oxidative stability. The SEM image of TiO2 NPs and HB‐SPAAKs/TiO2 nanocomposites membrane clearly showed the spherical of TiO2 and porous structure of HB‐SPAAKs with a pore diameter of 2–50 μm. TEM image reveals the uniform particle size distribution of TiO2 nanoparticles having a nanosize of 100 nm. TiO2 loaded polymer nanocomposites showed lower values of W/U and S/R when compared to the unmodified HB‐SPAAK, while 3% TiO2 loaded HB‐SPAAKs exhibited a threefold increment of proton conductivity of 1.439 × 10−2 S cm−1 compared to HB‐SPAAKs (0.41 x 10−2 S cm−1) and lower than that of Nafion 117 (0.1003 S cm−1 at 80°C). The 5% TiO2 NPs‐embedded with HB‐SPAAKs nanocomposites membranes also presented admirable oxidative stability with a degradation value of 13.8% during immersion in Fenton reagent for 8 h at 70°C.