Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions

The striatum of humans and other mammals is divided into macroscopic compartments made up of a labyrinthine striosome compartment embedded in a much larger surrounding matrix compartment. Anatomical and snRNA-Seq studies of the Huntington’s disease (HD) postmortem striatum suggest a preferential decline of some striosomal markers, and mRNAs studies of HD model mice concur. Here, by immunohistochemical methods, we examined the distribution of the canonical striosomal marker, mu-opioid receptor 1 (MOR1), in the striatum of the Q175 knock-in mouse model of HD in a postnatal time series extending from 3 to 19 months. We demonstrate that, contrary to the loss of many markers for striosomes, there is a pronounced up-regulation of MOR1 in these Q175 knock-in mice. We show that in heterozygous Q175 knock-in model mice [~192 cytosine-adenine-guanine (CAG) repeats], this MOR1 up-regulation progressed with advancing age and disease progression, and was particularly remarkable at caudal levels of the striatum. Given the known importance of MOR1 in basal ganglia signaling, our findings, though in mice, should offer clues to the pathogenesis of psychiatric features, especially depression, reinforcement sensitivity, and involuntary movements in HD.
Systematically Characterizing A-to-I RNA Editing Neoantigens in Cancer

A-to-I RNA editing can contribute to the transcriptomic and proteomic diversity of many diseases including cancer. It has been reported that peptides generated from RNA editing could be naturally presented by human leukocyte antigen (HLA) molecules and elicit CD8+ T cell activation. However, a systematical characterization of A-to-I RNA editing neoantigens in cancer is still lacking. Here, an integrated RNA-editing based neoantigen identification pipeline PREP (P rioritizing of R NA Editing-based Peptides) was presented. A comprehensive RNA editing neoantigen profile analysis on 12 cancer types from The Cancer Genome Atlas (TCGA) cohorts was performed. PREP was also applied to 14 ovarian tumor samples and two clinical melanoma cohorts treated with immunotherapy. We finally proposed an RNA editing neoantigen immunogenicity score scheme, i.e. REscore, which takes RNA editing level and infiltrating immune cell population into consideration. We reported variant peptide from protein IFI30 in breast cancer which was confirmed expressed and presented in two samples with mass spectrometry data support. We showed that RNA editing neoantigen could be identified from RNA-seq data and could be validated with mass spectrometry data in ovarian tumor samples. Furthermore, we characterized the RNA editing neoantigen profile of clinical melanoma cohorts treated with immunotherapy. Finally, REscore showed significant associations with improved overall survival in melanoma cohorts treated with immunotherapy. These findings provided novel insights of cancer biomarker and enhance our understanding of neoantigen derived from A-to-I RNA editing as well as more types of candidates for personalized cancer vaccines design in the context of cancer immunotherapy.
Salt Stress Tolerance of Dark Septate Endophytes Is Independent of Melanin Accumulation

Dark septate endophytes (DSEs) represent a diverse group of root-endophytic fungi that have been isolated from plant roots in many different natural and anthropogenic ecosystems. Melanin is widespread in eukaryotic organisms and possesses various functions such as protecting human skin from UV radiation, affecting the virulence of pathogens, and playing a role in development and physiology of insects. Melanin is a distinctive feature of the cell walls of DSEs and has been thought to protect these fungi from abiotic stress. Melanin in DSEs is assumed to be synthesized via the 1,8-dihydroxynaphthalene (DHN) pathway. Its function in alleviation of salt stress is not yet known. The aims of this study were: (i) investigating the growth responses of three DSEs (Periconia macrospinosa, Cadophora sp., and Leptodontidium sp.) to salt stress, (ii) analyzing melanin production under salt stress and, (iii) testing the role of melanin in salt stress tolerance of DSEs. The study shows that the three DSE species can tolerate high salt concentrations. Melanin content increased in the hyphae of all DSEs at 100 mM salt, but decreased at 500 mM. This was not reflected in the RNA accumulation of the gene encoding scytalone dehydratase which is involved in melanin biosynthesis. The application of tricyclazole, a DHN-melanin biosynthesis inhibitor, did not affect either salt stress tolerance or the accumulation of sodium in the hyphae. In addition, melanin biosynthesis mutants of Leptodontidium sp. did not show decreased growth performance compared to the wild-type, especially not at high salt concentrations. This indicates that DSEs can live under salt stress and withstand these conditions regardless of melanin accumulation.
Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy

At 96 weeks after unilateral intravitreal injection of rAAV2/2-ND4, vision improved in both eyes in 78% of subjects affected with LHON. Unexpected transfer Gene therapy using adeno-associated viral (AAV) vectors is a promising strategy for monogenic blinding diseases. Leber hereditary optic neuropathy (LHON) is caused by mutations in mitochondrial DNA (mtDNA), and a recombinant AAV, rAAV2/2-ND4, has shown therapeutic effects in a mouse model of LHON. Yu-Wai-Man et al. carried out a phase 3 clinical trial in 37 subjects with LHON bearing a MT-ND4 mutation. Although only one eye in each subject was treated, the authors reported sustained vision improvement in both eyes. Investigative analysis in nonhuman primates showed evidence of viral vector DNA transfer from the injected to the contralateral eye. REVERSE is a randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial that evaluated the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON). A total of 37 subjects carrying the m.11778G>A (MT-ND4) mutation and with duration of vision loss between 6 to 12 months were treated. Each subject’s right eye was randomly assigned in a 1:1 ratio to treatment with rAAV2/2-ND4 (GS010) or sham injection. The left eye received the treatment not allocated to the right eye. Unexpectedly, sustained visual improvement was observed in both eyes over the 96-week follow-up period. At week 96, rAAV2/2-ND4–treated eyes showed a mean improvement in best-corrected visual acuity (BCVA) of −0.308 LogMAR (+15 ETDRS letters). A mean improvement of −0.259 LogMAR (+13 ETDRS letters) was observed in the sham-treated eyes. Consequently, the primary end point, defined as the difference in the change in BCVA from baseline to week 48 between the two treatment groups, was not met (P = 0.894). At week 96, 25 subjects (68%) had a clinically relevant recovery in BCVA from baseline in at least one eye, and 29 subjects (78%) had an improvement in vision in both eyes. A nonhuman primate study was conducted to investigate this bilateral improvement. Evidence of transfer of viral vector DNA from the injected eye to the anterior segment, retina, and optic nerve of the contralateral noninjected eye supports a plausible mechanistic explanation for the unexpected bilateral improvement in visual function after unilateral injection.
Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

Macrophages (Mφ) are immune cells that exhibit remarkable functional plasticity. Identification of novel endogenous factors that can regulate plasticity and innate immune functions of Mφ will unravel new strategies to curb immune-related diseases. Long non-coding RNAs (lncRNAs) are a class of endogenous, non-protein coding, regulatory RNAs that are increasingly being associated with various cellular functions and diseases. Despite their ubiquity and abundance, lncRNA-mediated epigenetic regulation of Mφ polarization and innate immune functions is poorly studied. This study elucidates the regulatory role of lncRNAs in monocyte to Mφ differentiation, M1/M2 dichotomy and innate immune responses. Expression profiling of eighty-eight lncRNAs in monocytes and in vitro differentiated M2 Mφ identified seventeen differentially expressed lncRNAs. Based on fold-change and significance, we selected four differentially expressed lncRNAs viz., RN7SK, GAS5, IPW, and ZFAS1 to evaluate their functional impact. LncRNA knockdown was performed on day 3 M2 Mφ and the impact on polarization was assessed on day 7 by surface marker analysis. Knockdown of RN7SK and GAS5 showed downregulation of M2 surface markers (CD163, CD206, or Dectin) and concomitant increase in M1 markers (MHC II or CD23). RN7SK or GAS5 knockdown showed no significant impact on CD163, CD206, or CD23 transcripts. M1/M2 markers were not impacted by IPW or ZFAS1 knockdown. Functional regulation of antigen uptake/processing and phagocytosis, two central innate immune pathways, by candidate lncRNA was assessed in M1/M2 Mφ. Compared to scramble, enhanced antigen uptake and processing were observed in both M1/M2 Mφ transfected with siRNA targeting GAS5 and RN7SK but not IPW and ZFAS1. In addition, knockdown of RN7SK significantly augmented uptake of labelled E. coli in vitro by M1/M2 Mφ, while no significant difference was in GAS5 silencing cells. Together, our results highlight the instrumental role of lncRNA (RN7SK and GAS5)-mediated epigenetic regulation of macrophage differentiation, polarization, and innate immune functions.
Complex processes in simple ices : laboratory and observational studies of gas-grain interactions during star formation

During solar-type star formation, the chemistry evolves towards the formation of complex organic molecules, eventually setting the stage for the origin of life. This astrochemical evolution depends on the interaction between gas and microscopic interstellar grains, producing icy grain mantles. This thesis combines ice and gas-phase observations with astrophysically relevant laboratory simulations to constrain some of the key gas-grain processes. From Spitzer observations, the first simple ices, e.g. water and methane, form sequentially through condensation followed by an active surface chemistry, with more source-to-source variation the later in the sequence an ice forms. Close to the protostar the ices are heated. Experiments and their modeling have provided a generalized, quantitative understanding of the induced ice mixture evaporation and segregation, based on relative diffusion barriers alone. When no heat is available UV-induced evaporation still connects the ice and gas; UV photodesorption is found experimentally to be efficient with a similar yield for most ices. UV irradiation also converts simple ices into more complex species and this formation process has been quantified in situ for the first time. Based on these experiments, observations of complex organic molecules around protostars and in comets are readily explained by ice photochemistry.
Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

Background Lung cancer remains a common malignancy and the leading cause of cancer-related deaths in the world. Although dramatic progress made in multimodal therapies, it still has a poor prognosis. The Family with sequence similarity 83 (FAM83) of poorly characterized proteins are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini, most of which significantly elevated levels of expression in multiple cancers. However, the expression and prognostic values of different FAM83 family in lung cancer, especially in non-small-cell lung cancer (NSCLC), have not been clarified. Methods ONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, cBioPortal, and STRING databases were utilized in this study. Results The transcriptional levels of FAM83A/B/C/D/F/G/H were up-regulated in patients with NSCLC. A noticeable correlation was found between the over-expressions of FAM83A/B/D/F/H and clinical cancer stages in NSCLC patients. Besides, higher mRNA expressions of FAM83A/B/C/D/F/H were discovered to be expressively associated with overall survival (OS) in lung cancer patients, furthermore, FAM83A, FAM83C, and FAM83H in OS group achieved 0.9475/1, 0.971897/1, and 0.9454545/0.8974359 specificity/sensitivity in distinguishing short survivors from long survivors, respectively. Moreover, a high mutation rate of FAM83 family (51%) was also observed in lung adenocarcinoma (LUAD) patients, and genetic alteration in the FAM83 family was associated with shorter OS and disease-free survival (DFS) in LUAD patients. Conclusion Our results indicated that FAM83A/H might play important roles in NSCLC tumorigenesis and might be risk factor for the survival of NSCLC patients.
Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models

Organ-on-chip (OOC) systems recapitulate key biological processes and responses in vitro exhibited by cells, tissues, and organs in vivo. Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of in vivo behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating in vivo physiology in health and disease.
Measures to Control Invasive Crayfish Species in Switzerland: A Success Story?

Invasive crayfish species were first documented in Switzerland in the 1970s. Today, North American crayfish species dominate in most major lakes and streams in Switzerland. In combination with the crayfish plague, they pose a substantial threat to our native crayfish. Over the past 20 years, various techniques have been applied to reduce negative impacts of these invasive crayfish in Switzerland: eradication (temporary drainage or destruction of a water system, biocides), suppression (intensive trapping, electricity introduction of predatory fish) and containment (construction of crayfish barriers). Temporary drainage or filling-in of isolated ponds, in combination with calcium hydroxide application has been successful in eradicating populations of invasive crayfish. However, trapping and introduction of predatory fish led to a reduction in population density but neither method has ever caused the extinction of a population. Invasive crayfish have not yet reached crayfish barriers, therefore, long-term functionality of these barriers still needs to be proven. Nevertheless, functional controls with native crayfish have shown that barriers prevent their upstream movement. Implementation of crayfish barriers is the most promising method to protect native crayfish from displacement by invasive crayfish species. Many measures are expensive, time consuming, and show little or no success in controlling invasive crayfish. Therefore, we recommend to focus on implementing drastic measures, such as filling-in or draining of isolated waters or a combination of various methods to maximise the reduction of population size.
Adaptive Memory: Independent Effects of Survival Processing and Reward Motivation on Memory

Humans preferentially remember information processed for their survival relevance, a memorial benefit known as the survival processing effect. Memory is also biased towards information associated with the prospect of reward. Given the adaptiveness of these effects, they may depend on similar mechanisms. We tested whether motivation drives both effects, with reward incentives that are known to boost extrinsic motivation and survival processing perhaps stimulating intrinsic motivation. Accordingly, we manipulated survival processing and reward incentive independently during an incidental-encoding task in which participants chose between pairs of words concerning their relevance for a scenario, and examined the effects on encoding event-related potentials (ERP) activity and later performance on a surprise recall test. We hypothesized that if survival processing fosters intrinsic motivation, it should reduce the beneficial effects of extrinsic motivation (reward incentive). In contrast to this prediction, we found that reward incentive and survival processing independently improved memory and that the P300, a measure of lower-level cognitive resource allocation, was increased by reward incentive independent of survival processing. Further, survival processing and reward incentive independently increased the frontal slow wave (FSW), a measure of higher-level elaboration. These findings suggest that while survival processing and reward incentive may both increase encoding elaboration, the memory-enhancing effect of survival processing does not depend on increased intrinsic motivation. Additionally, we replicated a recent finding whereby the survival processing effect generalizes to a choice-based encoding task and further showed that the beneficial effect of choice on memory likely does not interact with either survival processing or reward.
Stress Reduction Techniques for Health Care Providers Dealing With Severe Coronavirus Infections (SARS, MERS, and COVID-19): A Rapid Review

Objective A rapid review was conducted to identify the most effective stress reduction techniques for health care providers dealing with patients infected with severe coronavirus (SARS, MERS, and COVID-19). Methods PubMed, PsychInfo, Embase, and CINAHL databases were searched to identify relevant studies. Searches were restricted by date (2000 until present). All empirical quantitative and qualitative studies in which relaxation techniques of various types implemented on health care providers caring for patients during severe coronavirus pandemics and articles that consider the implementation of mental health care services considered to be pertinent, such as commentaries, were included. Results Fourteen studies met the selection criteria, most of which were recommendations. Only one study described a digital intervention, and user satisfaction was measured. In the recommendations, both organizational and individual self-care interventions were suggested. Conclusions Further research is necessary to establish tailor-made effective stress reduction interventions for this population, during these challenging and particular times.
Using Habitat Classification to Assess Representativity of a Protected Area Network in a Large, Data-Poor Area Targeted for Deep-Sea Mining

Extractive activities in the ocean are expanding into the vast, poorly studied deep sea, with the consequence that environmental management decisions must be made for data-poor seafloor regions. Habitat classification can support marine spatial planning and inform decision-making processes in such areas. We present a regional, top–down, broad-scale, seafloor-habitat classification for the Clarion-Clipperton Fracture Zone (CCZ), an area targeted for future polymetallic nodule mining in abyssal waters in the equatorial Pacific Ocean. Our classification uses non-hierarchical, k-medoids clustering to combine environmental correlates of faunal distributions in the region. The classification uses topographic variables, particulate organic carbon flux to the seafloor, and is the first to use nodule abundance as a habitat variable. Twenty-four habitat classes are identified, with large expanses of abyssal plain and smaller classes with varying topography, food supply, and substrata. We then assess habitat representativity of the current network of protected areas (called Areas of Particular Environmental Interest) in the CCZ. Several habitat classes with high nodule abundance are common in mining exploration claims, but currently receive little to no protection in APEIs. There are several large unmanaged areas containing high nodule abundance on the periphery of the CCZ, as well as smaller unmanaged areas within the central CCZ, that could be considered for protection from mining to improve habitat representativity and safeguard regional biodiversity.
Severe Acute Respiratory Syndrome Coronavirus 2-Induced Neurological Complications

Our review aims to highlight the neurological complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the available treatments according to the existing literature, discussing the underlying mechanisms. Since the end of 2019, SARS-CoV-2 has induced a worldwide pandemic that has threatened numerous lives. Fever, dry cough, and respiratory symptoms are typical manifestations of COVID-19. Recently, several neurological complications of the central and peripheral nervous systems following SARS-CoV-2 infection have gained clinicians' attention. Encephalopathy, stroke, encephalitis/meningitis, Guillain–Barré syndrome, and multiple sclerosis are considered probable neurological signs of COVID-19. The virus may invade the nervous system directly or induce a massive immune inflammatory response via a “cytokine storm. ” Specific antiviral drugs are still under study. To date, immunomodulatory therapies and supportive treatment are the predominant strategies. In order to improve the management of COVID-19 patients, it is crucial to monitor the onset of new neurological complications and to explore drugs/vaccines targeted against SARS-CoV-2 infection.