Miracle-dz/UniFAR-FTUs huggingface dataset:
Ancient plant DNA reveals High Arctic greening during the Last Interglacial

Significance The Arctic is warming exceptionally rapidly, promoting an expansion of shrubs across the Arctic with global-scale climate implications. The Last Interglacial (∼125,000 y ago) was the most recent time the Arctic was warmer than present and thus serves as an analogue for Arctic greening in the near future. Ancient plant DNA in lake sediment from this time reveals major ecosystem changes in response to warmth, including an ∼400 km northward shift of dwarf birch relative to today. Enhanced shrub cover, corroborated by molecular and microfossil analyses, amplified warming during the Last Interglacial and will likely play a similar role in the future. This record constitutes the oldest authenticated plant DNA from lake sediment yet reported, increasing the technique’s temporal potential. Summer warming is driving a greening trend across the Arctic, with the potential for large-scale amplification of climate change due to vegetation-related feedbacks [Pearson et al., Nat. Clim. Chang. (3), 673–677 (2013)]. Because observational records are sparse and temporally limited, past episodes of Arctic warming can help elucidate the magnitude of vegetation response to temperature change. The Last Interglacial ([LIG], 129,000 to 116,000 y ago) was the most recent episode of Arctic warming on par with predicted 21st century temperature change [Otto-Bliesner et al., Philos. Trans. A Math. Phys. Eng. Sci. (371), 20130097 (2013) and Post et al., Sci. Adv. (5), eaaw9883 (2019)]. However, high-latitude terrestrial records from this period are rare, so LIG vegetation distributions are incompletely known. Pollen-based vegetation reconstructions can be biased by long-distance pollen transport, further obscuring the paleoenvironmental record. Here, we present a LIG vegetation record based on ancient DNA in lake sediment and compare it with fossil pollen. Comprehensive plant community reconstructions through the last and current interglacial (the Holocene) on Baffin Island, Arctic Canada, reveal coherent climate-driven community shifts across both interglacials. Peak LIG warmth featured a ∼400-km northward range shift of dwarf birch, a key woody shrub that is again expanding northward. Greening of the High Arctic—documented here by multiple proxies—likely represented a strong positive feedback on high-latitude LIG warming. Authenticated ancient DNA from this lake sediment also extends the useful preservation window for the technique and highlights the utility of combining traditional and molecular approaches for gleaning paleoenvironmental insights to better anticipate a warmer future.
Underrepresentation of Phenotypic Variability of 16p13.11 Microduplication Syndrome Assessed With an Online Self-Phenotyping Tool (Phenotypr): Cohort Study

Background 16p13.11 microduplication syndrome has a variable presentation and is characterized primarily by neurodevelopmental and physical phenotypes resulting from copy number variation at chromosome 16p13.11. Given its variability, there may be features that have not yet been reported. The goal of this study was to use a patient “self-phenotyping” survey to collect data directly from patients to further characterize the phenotypes of 16p13.11 microduplication syndrome. Objective This study aimed to (1) discover self-identified phenotypes in 16p13.11 microduplication syndrome that have been underrepresented in the scientific literature and (2) demonstrate that self-phenotyping tools are valuable sources of data for the medical and scientific communities. Methods As part of a large study to compare and evaluate patient self-phenotyping surveys, an online survey tool, Phenotypr, was developed for patients with rare disorders to self-report phenotypes. Participants with 16p13.11 microduplication syndrome were recruited through the Boston Children's Hospital 16p13.11 Registry. Either the caregiver, parent, or legal guardian of an affected child or the affected person (if aged 18 years or above) completed the survey. Results were securely transferred to a Research Electronic Data Capture database and aggregated for analysis. Results A total of 19 participants enrolled in the study. Notably, among the 19 participants, aggression and anxiety were mentioned by 3 (16%) and 4 (21%) participants, respectively, which is an increase over the numbers in previously published literature. Additionally, among the 19 participants, 3 (16%) had asthma and 2 (11%) had other immunological disorders, both of which have not been previously described in the syndrome. Conclusions Several phenotypes might be underrepresented in the previous 16p13.11 microduplication literature, and new possible phenotypes have been identified. Whenever possible, patients should continue to be referenced as a source of complete phenotyping data on their condition. Self-phenotyping may lead to a better understanding of the prevalence of phenotypes in genetic disorders and may identify previously unreported phenotypes.
Correlation of Lgr5 expression with clinicopathological features of colorectal cancer and its diagnostic and prognostic values.

PURPOSE To investigate the relationship between Leucine-rich repeat G-protein coupled receptor 5 (Lgr5) expression and clinicopathological features of colorectal cancer and its diagnostic and prognostic values. METHODS The cancer and adjacent tissues of 98 patients with colorectal cancer undergoing resection in Jiangsu Cancer Hospital from 2011 to 2013 were enrolled. The intestinal mucosal tissue of 50 healthy subjects was enrolled as a control group. Western blot was used to detect the expression level of Lgr5 in colorectal cancer, Kaplan-Meier method to analyze the correlation of Lgr5 expression with the 5-year survival rate, Cox regression to analyze prognostic risk factors for the patients, and receiver operating characteristics (ROC) curve to analyze the diagnostic value of Lgr5 of the disease. RESULTS The expression level of Lgr5 in the intestinal mucosal and adjacent tissues was significantly lower than that in the cancer tissue (p<0.05). The 5-year survival in the Lgr5 low expression group was higher than that in the Lgr5 high expression group (p=0.002). Lgr5 was an independent risk factor for the prognosis of colorectal cancer. The sensitivity, specificity and the area under the curve (AUC) of Lgr5 were 90.00%, 79.59% and 0.880, respectively (p<0.001). CONCLUSION Patients with a low 5-year survival rate have a high expression of Lgr5, which is closely related to the clinical staging, differentiation, depth of infiltration, lymph node metastasis, vascular invasion, liver metastasis and distant metastasis. Lgr5 is an independent prognostic risk factor for the patients and a better indicator for the diagnosis of colorectal cancer.
Mineralogy and crystal chemistry of Mn, Fe, Co, Ni, and Cu in a deep-sea Pacific polymetallic nodule

Abstract Minor-element concentrations in marine ferromanganese nodules are primarily controlled by the mineralogy, which itself depends on redox conditions at the sediment-water interface. Results are presented for the first in-depth X-ray microstructural and microspectroscopic investigation of a mixed hydrogenetic-diagenetic nodule, which is representative of ferromanganese deposits on abyssal plains. The measurements were conducted by micro-X-ray diffraction and X-ray absorption spectroscopy (both XANES and EXAFS) on hydrogeneous and diagenetic regions of the nodule. The hydrogeneticdiagenetic interface was imaged by X-ray microfluorescence, after which regions of interest were chosen to represent mineralogical and chemical transformations that occurred at the early stage of suboxic diagenesis. In the hydrogenetic nodule (oxic environment), Mn is speciated as Fe-vernadite, a nanocomposite material composed of intergrown feroxyhite (δ-FeOOH) and monodispersed phyllomanganate layers having no interlayer Mn (vernadite). In the diagenetic nodule (suboxic environment), Mn is speciated dominantly as Mg-rich 10 Å vernadite, which consists of a random intergrowth of vernadite and its transformation product todorokite. The authigenic 10 Å vernadite precipitated from the components of vernadite in Fe-vernadite that were dissolved in suboxic microenvironments of the sediment. Direct evidence supporting a redox-driven dissolution reaction is provided by the valence composition of Mn, as measured by micro-XANES, which is 0.69Mn4++ 0.24Mn3++ 0.07Mn2+ (average = 3.62 ± 0.04 v.u.) for Fe-vernadite and 0.61Mn4+ + 0.23Mn3+ + 0.16Mn2+ (average 3.28 ± 0.04 v.u.) for 10 Å vernadite. Ni and Cu, derived mainly from dissolved vernadite and oxidized organic matter, replace structural Mn3+/4+ in both the MnO2 layer and todorokite domains of 10 Å vernadite. Pure todorokite in highly diagenetic regions of the nodule has an average formula of Mg2+0.167(Mn4+0.783 Mn3+0.099Co3+0.002Ni2+0.076Cu2+0.040)O2·nH2O, with an atomic ratio of (Cu+Ni+Co)/Mn = 0.13, which is slightly lower than 0.167 (⅙), the maximum metal uptake capacity reported for marine nodules. By analogy with synthetic todorokites we infer that Mg2+, which has a hydrated diameter close to that of the [3 × 3] tunnel size of todorokite, and Mn3+ and Cu2+, which prefer Jahn-Teller distorted octahedra, play a crucial role in templating the topotactic transformation of 10 Å vernadite to todorokite and stabilizing todorokite in suboxic marine sediments.
Effect of new Medicare enrollment on health, healthcare utilization, and cost: A scoping review

More than three million Americans turn 65 each year and newly enroll in Medicare, making this one of the most common insurance transitions. Non‐Medicare insurance transitions are associated with changes in health, healthcare utilization and costs. In addition, older Americans have higher morbidity, mortality, healthcare utilization, and healthcare costs than the general population. However, the effect of new Medicare enrollment on these outcomes is unclear.
Updated perspectives on awake neurosurgery with cognitive and emotional assessment for patients with low-grade gliomas

ABSTRACT Introduction: Thanks to early extensive surgical resection combined with medical oncological therapies, life expectancy dramatically increased in low-grade glioma (LGG), with an overall survival currently over 15 years. Therefore, patients should be able to maintain valuable family and socio-professional activities. Areas covered: For many decades, cognitive and emotional aspects were neglected by surgical and medical neurooncologists. The goal of surgery was to avoid hemiplegia and/or aphasia, with no considerations regarding behavior. However, because LGG patients live longer, they must be cognitively and affectively able to make long-term projects. Preservation of higher-order functions should be considered systematically in LGG surgery by means of awake cognitive/emotional mapping and monitoring. Expert opinion: The aim is to incorporate recent advances in neurosciences, which proposed revisited models of cerebral processing relying on a meta-network perspective, into the pre-, intra- and postoperative procedure. In this connectomal approach, brain functions result from complex interactions within and between neural networks. This improved understanding of a constant instability of the neural system allows a better cognitive/emotional assessment before and after each treatment over years, in order to preserve personality and adaptive behavior for each LGG patient, based on his/her own definition of quality of life. It is time to create oncological neurosciences.
RNA helicase-mediated regulation of snoRNP dynamics on pre-ribosomes and rRNA 2′-O-methylation

Abstract RNA helicases play important roles in diverse aspects of RNA metabolism through their functions in remodelling ribonucleoprotein complexes (RNPs), such as pre-ribosomes. Here, we show that the DEAD box helicase Dbp3 is required for efficient processing of the U18 and U24 intron-encoded snoRNAs and 2′-O-methylation of various sites within the 25S ribosomal RNA (rRNA) sequence. Furthermore, numerous box C/D snoRNPs accumulate on pre-ribosomes in the absence of Dbp3. Many snoRNAs guiding Dbp3-dependent rRNA modifications have overlapping pre-rRNA basepairing sites and therefore form mutually exclusive interactions with pre-ribosomes. Analysis of the distribution of these snoRNAs between pre-ribosome-associated and ‘free’ pools demonstrated that many are almost exclusively associated with pre-ribosomal complexes. Our data suggest that retention of such snoRNPs on pre-ribosomes when Dbp3 is lacking may impede rRNA 2′-O-methylation by reducing the recycling efficiency of snoRNPs and by inhibiting snoRNP access to proximal target sites. The observation of substoichiometric rRNA modification at adjacent sites suggests that the snoRNPs guiding such modifications likely interact stochastically rather than hierarchically with their pre-rRNA target sites. Together, our data provide new insights into the dynamics of snoRNPs on pre-ribosomal complexes and the remodelling events occurring during the early stages of ribosome assembly.
α1-Antitrypsin: Key Player or Bystander in Acute Respiratory Distress Syndrome?

Acute respiratory distress syndrome is characterized by hypoxemia, altered alveolar–capillary permeability, and neutrophil-dominated inflammatory pulmonary edema. Despite decades of research, an effective drug therapy for acute respiratory distress syndrome remains elusive. The ideal pharmacotherapy for acute respiratory distress syndrome should demonstrate antiprotease activity and target injurious inflammatory pathways while maintaining host defense against infection. Furthermore, a drug with a reputable safety profile, low possibility of off-target effects, and well-known pharmacokinetics would be desirable. The endogenous 52-kd serine protease α1-antitrypsin has the potential to be a novel treatment option for acute respiratory distress syndrome. The main function of α1-antitrypsin is as an antiprotease, targeting neutrophil elastase in particular. However, studies have also highlighted the role of α1-antitrypsin in the modulation of inflammation and bacterial clearance. In light of the current SARS-CoV-2 pandemic, the identification of a treatment for acute respiratory distress syndrome is even more pertinent, and α1-antitrypsin has been implicated in the inflammatory response to SARS-CoV-2 infection. New therapies are urgently required for acute respiratory distress syndrome, particularly in the context of the current SARS-CoV-2 pandemic. The endogenously produced protein α1-antitrypsin is a potential treatment option because of its potent antielastase, immunomodulatory, and bactericidal effects.
Avaliação da resposta ao stresse oxidativo induzido por cádmio e cobre em plantas de tabaco transformadas e não transformadas

The response of tobacco plants (Nicotiana tabacum L.) non-transformed (WT) and transformed (B1F and B5H) with AtTPS1, the trehalose-6-phosphate-synthase gene from Arabidopsis, to cadmium (50, 200 μM) and copper (100, 400 μM) was compared. Protein content, antioxidative enzymes (CAT, POD, SOD, APX), lipid peroxidation and hydrogen peroxide were determined in leaves. WT showed a significant increase in malondialdehyde content both with Cd and Cu, indicating occurrence of lipid peroxidation. B5H and B1F showed lower incidence of lipid peroxidation. SOD activity showed no significant variation both with Cd and Cu, indicating that superoxide formation was not induced by these heavy metals. POD role in the scavenging of H2O2 was more relevant in WT than in B5H and B1F.CAT seems to be more important in B5H and B1F than in WT, with higher activity compared to WT. APX showed a significant increase in activity levels in B5H, both with Cd and Cu, indicating an important role in the elimination of H2O2. However, H2O2 removal by APX was not capable of reducing H2O2 levels that remained significantly higher than the control. In conclusion, B1F plants seem to be less affected by oxidative stress induced by Cd and Cu than B5H or WT. Key-words: Cadmium, Copper, oxidative stress, antioxidant enzymes, Nicotiana tabacum L. , trehalose-6-phosphate-synthase.
ALIX and ceramide differentially control polarized small extracellular vesicle release from epithelial cells

Exosomes, important players in cell–cell communication, are small extracellular vesicles of endocytic origin. Although single cells are known to release various kinds of exosomes (referred to as exosomal heterogeneity), very little is known about the mechanisms by which they are produced and released. Here, we established methods of studying exosomal heterogeneity by using polarized epithelial cells and showed that distinct types of small extracellular vesicles (more specifically CD9‐ and CD63‐positive, Annexin I‐negative small extracellular vesicles, which we refer to as exosomes herein) are differentially secreted from the apical and basolateral sides of polarized epithelial cells. We also identify GPRC5C (G protein‐coupled receptor class C group 5 member C) as an apical exosome‐specific protein. We further demonstrate that basolateral exosome release depends on ceramide, whereas ALIX, an ESCRT (endosomal sorting complexes required for transport)‐related protein, not the ESCRT machinery itself, is required for apical exosome release. Thus, two independent machineries, the ALIX–Syntenin1–Syndecan1 machinery (apical side) and the sphingomyelinase‐dependent ceramide production machinery (basolateral side), are likely to be responsible for the polarized exosome release from epithelial cells.
By targeting apoptosis facilitator BCL2L13, microRNA miR-484 alleviates cerebral ischemia/reperfusion injury-induced neuronal apoptosis in mice

ABSTRACT Neuronal apoptosis was considered as one of the main factors of cerebral ischemia/reperfusion injury. Understanding the molecular regulatory mechanism of neuronal apoptosis under the cerebral ischemia/reperfusion injury may provide the novel therapeutic targets for cerebral ischemia/reperfusion injury. However, the molecular regulatory mechanism of neurons fate determination under the cerebral ischemia/reperfusion injury remains poorly understood. This study was aimed to delve into the related molecular mechanism of miR-484 on the regulation of cerebral ischemia/reperfusion injury-induced neuronal apoptosis in mice. In this study, quantitative real-time polymerase chain reaction assays revealed that the expression level of miR-484 was down-regulated in neurons following OGD. Then, CCK8 assay western blot assay, and flow cytometry assay verified that upregulation of miR-484 increased viability and inhibited apoptosis of neurons following OGD. Further bioinformatics methods and dual-luciferase reporter assay were applied together to anticipate and certify the interaction between miR-484 and BCL2L13. Finally, cerebral infarct size assessment and TUNEL staining confirmed that overexpression of miR-484 alleviated cerebral ischemia/reperfusion injury in mice, and overexpression of BCL2L13 could abolish the effect of miR-484-suppressed cell apoptosis. All these results suggested that miR-484 alleviates cerebral ischemia/reperfusion injury-induced neuronal apoptosis in mice by targeting apoptosis facilitator BCL2L13. Graphical Abstract
Selective disruption of trigeminal sensory neurogenesis and differentiation in a mouse model of 22q11.2 deletion syndrome

ABSTRACT 22q11.2 Deletion Syndrome (22q11DS) is a neurodevelopmental disorder associated with cranial nerve anomalies and disordered oropharyngeal function, including pediatric dysphagia. Using the LgDel 22q11DS mouse model, we investigated whether sensory neuron differentiation in the trigeminal ganglion (CNgV), which is essential for normal orofacial function, is disrupted. We did not detect changes in cranial placode cell translocation or neural crest migration at early stages of LgDel CNgV development. However, as the ganglion coalesces, proportions of placode-derived LgDel CNgV cells increase relative to neural crest cells. In addition, local aggregation of placode-derived cells increases and aggregation of neural crest-derived cells decreases in LgDel CNgV. This change in cell-cell relationships was accompanied by altered proliferation of placode-derived cells at embryonic day (E)9.5, and premature neurogenesis from neural crest-derived precursors, reflected by an increased frequency of asymmetric neurogenic divisions for neural crest-derived precursors by E10.5. These early differences in LgDel CNgV genesis prefigure changes in sensory neuron differentiation and gene expression by postnatal day 8, when early signs of cranial nerve dysfunction associated with pediatric dysphagia are observed in LgDel mice. Apparently, 22q11 deletion destabilizes CNgV sensory neuron genesis and differentiation by increasing variability in cell-cell interaction, proliferation and sensory neuron differentiation. This early developmental divergence and its consequences may contribute to oropharyngeal dysfunction, including suckling, feeding and swallowing disruptions at birth, and additional orofacial sensory/motor deficits throughout life.
Do Cardiovascular Risk Factors and Cardiovascular Disease Explain Sex Differences in Cognitive Functioning in Old Age?

Background: Sex differences in cognitive functioning in old age are known to exist yet are still poorly understood. Objective: This study examines to what extent differences in cardiovascular risk factors and cardiovascular disease between men and women explain sex differences in cognitive functioning. Methods: Data from 2,724 older adults from the Longitudinal Aging Study Amsterdam were used. Information processing speed and episodic memory, measured three times during six years of follow-up, served as outcomes. The mediating role of cardiovascular risk factors and cardiovascular disease was examined in single and multiple mediator models. Determinant-mediator effects were estimated using linear or logistic regression, and determinant-outcome and mediator-outcome effects were estimated using linear mixed models. Indirect effects were estimated using the product-of-coefficients estimator. Results: Women scored 1.58 points higher on information processing speed and 1.53 points higher on episodic memory. Several cardiovascular risk factors had small mediating effects. The sex difference in information processing speed was mediated by smoking, depressive symptoms, obesity, and systolic blood pressure. The sex difference in episodic memory was mediated by smoking, physical activity, and depressive symptoms. Effects of smoking, LDL cholesterol, and diabetes mellitus on information processing speed differed between men and women. Conclusion: Differences in cardiovascular risk factors between women and men partially explained why women had better cognitive functioning. A healthy cardiovascular lifestyle seems beneficial for cognition and sex-specific strategies may be important to preserve cognitive functioning at older age.