Miracle-dz/UniFAR-FTUs huggingface dataset:
Actin reduction by MsrB2 is a key component of the cytokinetic abscission checkpoint and prevents tetraploidy

Significance Cytokinesis concludes cell division by physically separating the daughter cells. Defects in cytokinesis result in tetraploid, binucleated cells that are genetically unstable and represent an important cause of tumorigenesis. The abnormal presence of lagging chromatin within the intercellular bridge (ICB) connecting the daughter cells is detected by an evolutionarily conserved abscission checkpoint, which delays abscission and stabilizes the ICB for hours, thereby preventing the formation of binucleated cells and DNA damage. Here, we show that the reductase MsrB2 enzymatically controls the polymerization of actin filaments in the ICB and prevents ICB instability specifically in the presence of lagging chromatin. This work thus reveals that actin reduction by MsrB2 is a key component of the abscission checkpoint. Abscission is the terminal step of cytokinesis leading to the physical separation of the daughter cells. In response to the abnormal presence of lagging chromatin between dividing cells, an evolutionarily conserved abscission/NoCut checkpoint delays abscission and prevents formation of binucleated cells by stabilizing the cytokinetic intercellular bridge (ICB). How this bridge is stably maintained for hours while the checkpoint is activated is poorly understood and has been proposed to rely on F-actin in the bridge region. Here, we show that actin polymerization is indeed essential for stabilizing the ICB when lagging chromatin is present, but not in normal dividing cells. Mechanistically, we found that a cytosolic pool of human methionine sulfoxide reductase B2 (MsrB2) is strongly recruited at the midbody in response to the presence of lagging chromatin and functions within the ICB to promote actin polymerization there. Consistently, in MsrB2-depleted cells, F-actin levels are decreased in ICBs, and dividing cells with lagging chromatin become binucleated as a consequence of unstable bridges. We further demonstrate that MsrB2 selectively reduces oxidized actin monomers and thereby counteracts MICAL1, an enzyme known to depolymerize actin filaments by direct oxidation. Finally, MsrB2 colocalizes and genetically interacts with the checkpoint components Aurora B and ANCHR, and the abscission delay upon checkpoint activation by nuclear pore defects also depends on MsrB2. Altogether, this work reveals that actin reduction by MsrB2 is a key component of the abscission checkpoint that favors F-actin polymerization and limits tetraploidy, a starting point for tumorigenesis.
Principal Component Regression for Forensic Age Determination Using the Raman Spectra of Teeth

Raman spectra of mineralized tooth tissues were used to build a principal component regression (PCR) age determination model for forensic application. A sample of 71 teeth was obtained from donors aging from 11 to 76 years. No particular selection criteria were applied; teeth affected with various pathological processes were deliberately included to simulate a realistic forensic scenario. In order to comply with the nondestructive specimen handling, Raman spectra were collected from tooth surfaces without any previous preparation. Different tooth tissues were evaluated by collecting the spectra from three distinct sites: tooth crown, tooth neck, and root apex. Whole recorded spectra (3500–200 cm−1) were used for principal component analysis and building of the age determination model using PCR. The predictive capabilities of the obtained age determination models varied according to the spectra collection site. Optimal age determination was attained by using Raman spectra collected from cementum at root apex (R2 values of 0.84 and 0.71 for male and female donors, respectively). For optimal performance of that model, male and female donors had to be analyzed separately, as merging both genders into a single model considerably diminished its predictive capability (R2 = 0.29).
Differential Behavioral and Neural Profiles in Youth With Conduct Problems During Risky Decision-Making.

Neuroimaging work has examined neural processes underlying risk taking in adolescence, yet predominantly in low-risk youth. To determine whether we can extrapolate from current neurobiological models, this functional magnetic resonance imaging study investigated risk taking and peer effects in youth with conduct problems (CP; N = 19) and typically developing youth (TD; N = 25). Results revealed higher real-life risk taking, lower risky decisions, and no peer effects on a risk-taking task in CP youth. CP youth showed greater ventral striatum (VS) activity during safe than risky decisions, whereas TD youth showed greater VS activation during risky decisions. Differential VS activity explained higher real-life risk taking in CP youth. Findings provide preliminary evidence that risk-taking behavior in youth with CD problems is characterized by differential neural patterns.
Censored quantile regression model with time‐varying covariates under length‐biased sampling

Quantile regression is a flexible and effective tool for modeling survival data and its relationship with important covariates, which often vary over time. Informative right censoring of data from the prevalent cohort within the population often results in length‐biased observations. We propose an estimating equation‐based approach to obtain consistent estimators of the regression coefficients of interest based on length‐biased observations with time‐dependent covariates. In addition, inspired by Zeng and Lin 2008, we also develop a more numerically stable procedure for variance estimation. Large sample properties including consistency and asymptotic normality of the proposed estimator are established. Numerical studies presented demonstrate convincing performance of the proposed estimator under various settings. The application of the proposed method is demonstrated using the Oscar dataset.
The functional interplay of lncRNA EGOT and HuR regulates hypoxia‐induced autophagy in renal tubular cells

Autophagy, an important cellular homeostatic mechanism regulates cell survival under stress and protects against acute kidney injury. However, the role of long noncoding RNA (lncRNA) in autophagy regulation in renal tubular cells (HK‐2) is unclear. The study was aimed to understand the importance of lncRNA in hypoxia‐induced autophagy in HK‐2 cells. LncRNA eosinophil granule ontogeny transcript (EGOT) was identified as autophagy‐associated lncRNA under hypoxia. The lncRNA EGOT expression was significantly downregulated in renal tubular cells during hypoxia‐induced autophagy. Gain‐ and loss‐of‐EGOT functional studies revealed that EGOT overexpression reduced autophagy by downregulation of ATG7, ATG16L1, LC3II expressions and LC 3 puncta while EGOT knockdown reversed the suppression of autophagy. Importantly, RNA‐binding protein, (ELAVL1)/Hu antigen R (HuR) binds and stabilizes the EGOT expression under normoxia and ATG7/16L1 expressions under hypoxia. Furthermore, HuR mediated stabilization of ATG7/16L1 expressions under hypoxia causes a decline in EGOT levels and thereby promotes autophagy. Altogether, the study first reveals the functional interplay of lncRNA EGOT and HuR on the posttranscriptional regulation of the ATG7/16L1 expressions. Thus, the HuR/EGOT/ATG7/16L1 axis is crucial for hypoxia‐induced autophagy in renal tubular cells.
uPA-mediated plasminogen activation is enhanced by polyphosphate

Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) differ in their modes of action. Efficient tPA-mediated plasminogen activation requires binding to fibrin. In contrast, uPA is fibrin independent and activates plasminogen in solution or when associated with its cellular receptor urokinase protease activated receptor (uPAR). We have previously shown that polyphosphate (polyP), alters fibrin structure and attenuates tPA and plasminogen binding to fibrin, thereby down-regulating fibrinolysis. Here we investigate the impact of polyP on uPA-mediated fibrinolysis. As previously reported polyP of an average chain length of 65 (polyP65) delays tPA-mediated fibrinolysis. The rate of plasmin generation was also delayed and reduced 1.6-fold in polyP65 -containing clots (0.74±0.06 vs. 1.17±0.14 pM/s in P<0.05). Analysis of tPA-mediated fibrinolysis in real-time by confocal microscopy was significantly slower in polyP65 -containing clots. In marked contrast, polyP65 augmented the rate of uPA-mediated plasmin generation 4.7-fold (3.96±0.34 vs. 0.84±0.08 pM/s; P<0.001) and acce-lerated fibrinolysis (t1/2 64.5±1.7 min vs. 108.2±3.8 min; P<0.001). Analysis of lysis in real-time confirmed that polyP65 enhanced uPA-mediated fibrino- lysis. Varying the plasminogen concentration (0.125-1 mM) in clots dose-dependently enhanced uPA-mediated fibrinolysis, while negligible changes were observed on tPA-mediated fibrinolysis. The accelerating effect of polyP65 on uPA-mediated fibrinolysis was overcome by additional plasminogen, while the down-regulation of tPA-mediated lysis and plasmin generation was largely unaffected. polyP65 exerts opposing effects on tPA- and uPA-mediated fibrinolysis, attenuating the fibrin cofactor function in tPA-media-ted plasminogen activation. In contrast, polyP may facilitate the interaction between fibrin-independent uPA and plasminogen thereby accelerating plasmin generation and downstream fibrinolysis.
Foliar Application of Polyamines Modulates Winter Oilseed Rape Responses to Increasing Cold

Cold stress is one of the most common abiotic stresses experienced by plants and is caused by low temperature extremes and variations. Polyamines (PAs) have been reported to contribute in abiotic stress defense processes in plants. The present study investigates the survival and responses of PA-treated non-acclimated (N) and acclimated (A) winter oilseed rape to increasing cold conditions. The study was conducted under controlled conditions. Seedlings were foliarly sprayed with spermidine (Spd), spermine (Spm), and putrescine (Put) solutions (1 mM) and exposed to four days of cold acclimation (4 °C) and two days of increasing cold (from −1 to −3 °C). Two cultivars with different cold tolerance were used in this study. The recorded traits included the percentage of survival, H+-ATPase activity, proline accumulation, and ethylene emission. Exogenous PA application improved cold resistance, maintained the activity of plasma membrane H+-ATPase, increased content of free proline, and delayed stimulation of ethylene emission under increasing cold. The results of the current study on winter oilseed rape revealed that foliar application of PAs may activate a defensive response (act as elicitor to trigger physiological processes), which may compensate the negative impact of cold stress. Thus, cold tolerance of winter oilseed rape can be enhanced by PA treatment.
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains

Not too sticky There is increasing evidence for a role of liquid-liquid phase separation (LLPS) in many cellular processes. Many proteins that undergo LLPS include prionlike domains (PLDs), which are enriched in polar amino acids and often interspersed with aromatic residues. Combining experimental data with simulations, Martin et al. quantified concentrations of PLDs in coexisting dilute and dense phases as a function of temperature and show that the phase behavior is determined by the number of aromatic residues and their patterning, with uniform patterning of aromatic residues promoting LLPS and inhibiting aggregation. They developed a sticker-and-spacers model that can predict the phase behavior of PLDs on the basis of their sequence. Science, this issue p. 694 A stickers-and-spacers model reproduces experimentally measured sequence-specific phase diagrams of prion-like domains. Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.
Expanding U.S. Laboratory Capacity for Neisseria gonorrhoeae Antimicrobial Susceptibility Testing and Whole-Genome Sequencing through the CDC's Antibiotic Resistance Laboratory Network

U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. ABSTRACT U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae. AR-Ng testing, a subactivity of the CDC’s AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC’s national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.
Nutritional status and intestinal parasites among young children from pastoralist communities of the Ethiopian Somali region

Abstract Pastoralist children in the Ethiopian Somali Regional State (ESRS) are at high risk for undernutrition and intestinal parasitic infections (IPIs). We assessed the nutritional status and its association with IPIs in 500 children <5 years of age in a clustered cross‐sectional study in Adadle district, ESRS. Stool samples were microscopically examined for IPIs and biomarkers for iron and vitamin A status, anthropometry, and food variety score (FVS) were assessed. Median (interquartile range [IQR]) FVS was 2.0 (2.0, 4.0), and 35% of children were exclusively breastfed up to age 6 months. Prevalence of stunting, wasting, underweight and mid‐upper arm circumference (MUAC) <12.5 cm was 30, 34, 40, and 16%, respectively. Median (IQR) haemoglobin, ferritin, and retinol‐binding protein concentrations were 9.5 g dL‐1 (8.2, 10.9), 6.2 μg L‐1 (4.0, 10.2), and 0.8 μmol L−1 (0.67, 0.91), respectively. Prevalence of anaemia, iron, and vitamin A deficiency was 75, 91, and 30%, respectively. IPIs' prevalence was 47%; the most prevalent IPIs were Giardia lamblia (22%) and Ascaris lumbricoides (15%). Giardial infections but not A. lumbricoides increased the risk for MUAC <12.5 cm (adjusted odds ratio [aOR]: 3.50, 95% confidence interval [CI] [2.21, 5.54]). The odds for anaemia were 97% (aOR: 0.03, 95% CI [0.03, 0.07]) and 89% (aOR: 0.11, 95% CI [0.11, 0.23]) less for children with FVS >2 or with exclusive breastfeeding up to 6 months, respectively. Undernutrition and IPIs are alarmingly high in <5 years of age children in ESRS. Giardial infections and low nutritional adequacy of the diet seem to be major contributing factors to the precarious nutritional status and should be addressed by appropriate interventions.
A low power and low ripple CMOS high voltage generator for RFID transponder EEPROM

A high-voltage generator (HVG) is an essential part of a radio frequency identification electrically erasable programmable read-only memory (RFID–EEPROM). An HVG circuit is used to generate a regulated output voltage that is higher than the power supply voltage. However, the performance of the HVG is affected owing to the high-power dissipation, high-ripple voltage and low-pumping efficiency. Therefore, a regulator circuit consists of a voltage divider, comparator and a voltage reference, which are respectively required to reduce the ripple voltage, increase pumping efficiency and decrease the power dissipation of the HVG. Conversely, a clock driving circuit consists of the current-starved ring oscillator (CSRO), and the non- overlapping clock generator is required to drive the clock signals of the HVG circuit. In this study, the Mentor Graphics EldoSpice software package is used to design and simulate the HVG circuitry. The results showed that the designed CSRO dissipated only 4.9 μW at 10.2 MHz and that the phase noise was only -119.38 dBc/Hz at 1 MHz. Moreover, the proposed charge pump circuit was able to generate a maximum VPP of 13.53 V and it dissipated a power of only 31.01 μW for an input voltage VDD of 1.8 V. After integrating all the HVG modules, the results showed that the regulated HVG circuit was also able to generate a higher VPP of 14.59 V, while the total power dissipated was only 0.12 mW with a chip area of 0.044 mm2. Moreover, the HVG circuit produced a pumping efficiency of 90% and reduced the ripple voltage to <4 mV. Therefore, the integration of all the proposed modules in HVG ensured low-ripple programming voltages, higher pumping efficiency, and EEPROMs with lower power dissipation, and can be extensively used in low-power applications, such as in non-volatile memory, radiofrequency identification transponders, on-chip direct current DC-DC converters.
The evolution of stem cells, disease modeling, and drug discovery for neurological disorders.

Human neurological disorders are amongst the most challenging areas of translational research. The difficulty of acquiring human neural samples or specific, representative animal models has necessitated a multifaceted approach to understanding disease pathology and drug discovery. The de-differentiation of somatic cells to human induced pluripotent stem cells (hiPSCs) for the generation of neural derivatives has broadened the capability of biomedical research to study human cell types in neurological disorders. The initial zeal for the potential of hiPSCs for immediate biomedical breakthroughs has evolved to more reasonable expectations. Over the past decade, hiPSC technology has demonstrated the capacity to successfully establish "disease in a dish" models of complex neurological disorders and to identify possible novel therapeutics. However, as hiPSCs are employed more broadly, an increased understanding of the limitations of hiPSC studies are becoming more evident. Here we review the challenges of studying neurological disorders, the current limitations of stem cell based disease modeling, and the degrees to which hiPSC studies to date have demonstrated the capacity to fill essential gaps in neurological research.
In transition: Avian biogeographic responses to a century of climate change across desert biomes

Transition zones between biomes, also known as ecotones, are areas of pronounced ecological change. They are primarily maintained by abiotic factors and disturbance regimes that could hinder or promote species range shifts in response to climate change. We evaluated how climate change has affected metacommunity dynamics in two adjacent biomes and across their ecotone by resurveying 106 sites that were originally surveyed for avian diversity in the early 20th century by Joseph Grinnell and colleagues. The Mojave, a warm desert, and the Great Basin, a cold desert, have distinct assemblages and meet along a contiguous, east–west boundary. Both deserts substantially warmed over the past century, but the Mojave dried while the Great Basin became wetter. We examined whether the distinctiveness and composition of desert avifaunas have changed, if species distributions shifted, and how the transition zone impacted turnover patterns. Avifauna change was characterized by (a) reduced occupancy, range contractions, and idiosyncratic species redistributions; (b) degradation of historic community structure, and increased taxonomic and climatic differentiation of the species inhabiting the two deserts; and (c) high levels of turnover at the transition zone but little range expansion of species from the warm, dry Mojave into the cooler, wetter Great Basin. Although both deserts now support more drier and warmer tolerant species, their bird communities still occupy distinct climatological space and differ significantly in climatic composition. Our results suggest a persistent transition zone between biomes contributes to limiting the redistribution of birds, and highlight the importance of understanding how transition zone dynamics impact responses to climate change.