Miracle-dz/UniFAR-FTUs huggingface dataset:
Trehalose 6-Phosphate Positively Regulates Fatty Acid Synthesis by Stabilizing WRINKLED1[OPEN]

Trehalose 6-phosphate binds to the KIN10 subunit of SnRK1 and inhibits it in a GRIK-dependent manner, positively regulating fatty acid synthesis by stabilizing WRINKLED1. WRINKLED1 (WRI1), the transcriptional activator of fatty acid synthesis, was recently identified as a target of KIN10, a catalytic α-subunit of the SUCROSE-NON-FERMENTING1-RELATED PROTEIN KINASE1 (SnRK1). We tested the hypothesis that trehalose 6-phosphate (T6P), a signal of cellular sucrose status, can regulate fatty acid synthesis by inhibiting SnRK1. Incubation of Brassica napus suspension cells in medium containing T6P, or overexpression of the Escherichia coli T6P synthase, OtsA, in Nicotiana benthamiana, significantly increased T6P levels, WRI1 levels, and fatty acid synthesis rates. T6P directly bound to purified recombinant KIN10 with an equilibrium dissociation constant (Kd) of 32 ± 6 μM based on microscale thermophoresis. GEMINIVIRUS REP-INTERACTING KINASE1 (GRIK1) bound to KIN10 (Kd 19 ± 3 μM) and activated it by phosphorylation. In the presence of T6P, the GRIK1-KIN10 association was weakened by more than 3-fold (Kd 68 ± 9.8 μM), which reduced both the phosphorylation of KIN10 and its activity. T6P-dependent inhibition of SnRK1 activity was reduced in extracts of individual Arabidopsis thaliana grik1 and grik2 mutants relative to the wild type, while SnRK1 activity in grik1 grik2 extracts was enhanced by T6P. These results indicate that the T6P sensitivity of SnRK1 in vivo is GRIK1/GRIK2 dependent. Based on our findings, we propose a mechanistic model that links sugar signaling and fatty acid homeostasis.
Longitudinal Relations Between Depressive Symptoms and Executive Functions From Adolescence to Early Adulthood: A Twin Study

Depression is associated with deficits in executive functions (EFs)—cognitive control abilities that regulate goal-directed thoughts and actions—but the etiology of these associations is unclear. We examined the relations between depressive symptoms and multiple EF latent variables in a population-based sample of 439 twin pairs assessed at mean ages 12, 17, and 23 years. Greater depressive symptoms negatively related to a Common EF factor capturing shared variance across response inhibition, working memory updating, and mental set shifting tasks, and also negatively related to an Updating-Specific factor, but not a Shifting-Specific factor. Cross-lagged panel models suggested that the Common EF correlations reflected within-wave associations rather than prospective effects, whereas the Updating-Specific correlations reflected associations of earlier depression levels with later Updating-Specific ability. Twin models were consistent with a model in which Common EF and Updating-Specific abilities relate to depression through correlated genetic risk, with no significant environmental correlations.
Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective regulation of clathrin-mediated endocytosis

Significance Clathrin-mediated endocytosis (CME) determines the internalization of receptors and their downstream signaling. We discovered that CME is differentially regulated by specific signaling kinases in cancer cells. In particular, ERK1/2-mediated phosphorylation of the FCH/F-BAR and double SH3 domains-containing protein 2 (FCHSD2) regulates CME and the trafficking and signaling activities of EGF receptors. This reciprocal interaction negatively regulates cancer proliferation and migration. The expression level of FCHSD2 is positively correlated with higher lung cancer patient survival rates. This study identifies signaling pathways that impinge on the endocytic machinery and reveals a molecular nexus for crosstalk between intracellular signaling and CME. Cancer cells specifically adapt this crosstalk as a determinant for tumor progression, which has implications for novel therapeutics against cancers. Clathrin-mediated endocytosis (CME) regulates the uptake of cell-surface receptors as well as their downstream signaling activities. We recently reported that signaling can reciprocally regulate CME in cancer cells and that this crosstalk can contribute to cancer progression. To further explore the nature and extent of the crosstalk between signaling and CME in cancer cell biology, we analyzed a panel of oncogenic signaling kinase inhibitors for their effects on CME across a panel of normal and cancerous cells. Inhibition of several kinases selectively affected CME in cancer cells, including inhibition of ERK1/2, which selectively inhibited CME by decreasing the rate of clathrin-coated pit (CCP) initiation. We identified an ERK1/2 substrate, the FCH/F-BAR and SH3 domain-containing protein FCHSD2, as being essential for the ERK1/2-dependent effects on CME and CCP initiation. Our data suggest that ERK1/2 phosphorylation activates FCHSD2 and regulates EGF receptor (EGFR) endocytic trafficking as well as downstream signaling activities. Loss of FCHSD2 activity in nonsmall cell lung cancer (NSCLC) cells leads to increased cell-surface expression and altered signaling downstream of EGFR, resulting in enhanced cell proliferation and migration. The expression level of FCHSD2 is positively correlated with higher NSCLC patient survival rates, suggesting that FCHSD2 can negatively affect cancer progression. These findings provide insight into the mechanisms and consequences of the reciprocal regulation of signaling and CME in cancer cells.
The social location of harm from others’ drinking in 10 societies

AIMS Survey data from 10 diverse countries were used to analyse the social location of harms from others' drinking: which segments of the population are more likely to be adversely affected by such harm, and how does this differ between societies? METHODS General-population surveys in Australia, Chile, India, Laos, New Zealand, Nigeria, Sri Lanka, Thailand, United States and Vietnam, with a primary focus on the social location of the harmed person by gender, age groups, rural/urban residence and drinking status. Harms from known drinkers were analysed separately from harms from strangers. RESULTS In all sites, risky or moderate drinkers were more likely than abstainers to report harm from the drinking of known drinkers, with risky drinkers the most likely to report harm. This was also generally true for harm from strangers' drinking, although the patterns were more mixed in Vietnam and Thailand. Harm from strangers' drinking was more often reported by males, while gender disparity in harm from known drinkers varied between sites. Younger adults were more likely to experience harm both from known drinkers and from strangers in some, but not all, societies. Only a few sites showed significant urban/rural differences, with disparities varying in direction. In multivariate analyses, most relationships remained, although some were no longer significant. CONCLUSION The social location of harms from others' drinking, whether known or a stranger, varies considerably between societies. One near-commonality among the societies is that those who are themselves risky drinkers are more likely to suffer harm from others' drinking.
p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis

We previously demonstrated that transmissible gastroenteritis virus (TGEV) could induce apoptosis through caspase signaling. However, apoptosis was not completely prevented by caspases inhibitors, suggesting that there may be a caspase-independent pathway involved in TGEV-induced cell apoptosis. In this study, we investigated the regulation of apoptosis-inducing factor (AIF) on TGEV-induced apoptotic pathway. Results indicated that AIF translocated from the mitochondria to nucleus during TGEV infection, and the AIF inhibitor, N-phenylmaleimide (NP), significantly attenuated the apoptosis. In addition, the translocation of AIF was inhibited by Veliparib (ABT-888), an inhibitor of poly (ADP-ribose) polymerase (PARP). And the reactive oxygen species (ROS) scavenger, pyrrolidinedithiocarbamic (PDTC), redistributed AIF in the mitochondria and nucleus in TGEV-infected cells. Moreover, the protein levels in nucleus and the mRNA levels of AIF were inhibited in the presence of the p53 inhibitor, piﬁthrin-α (PFT-α) or in TGEV-infected p53−/−cells. Furthermore, TGEV-induced apoptosis was blocked by combination of three or more inhibitors, such as pan caspase inhibitor Z-VAD-FMK, NP, ABT-888, PDTC, PFT-α, to treat PK-15 cells. Taken together, these results suggest that the p53- and ROS-mediated AIF pathway and caspase-dependent pathway were involved in TGEV-induced apoptosis.
CPDist: Deep Siamese Networks for Learning Distances Between Structured Preferences

Preference are central to decision making by both machines and humans. Representing, learning, and reasoning with preferences is an important area of study both within computer science and across the sciences. When working with preferences it is necessary to understand and compute the distance between sets of objects, e.g., the preferences of a user and a the descriptions of objects to be recommended. We present CPDist, a novel neural network to address the problem of learning to measure the distance between structured preference representations. We use the popular CP-net formalism to represent preferences and then leverage deep neural networks to learn a recently proposed metric function that is computationally hard to compute directly. CPDist is a novel metric learning approach based on the use of deep siamese networks which learn the Kendal Tau distance between partial orders that are induced by compact preference representations. We find that CPDist is able to learn the distance function with high accuracy and outperform existing approximation algorithms on both the regression and classification task using less computation time. Performance remains good even when CPDist is trained with only a small number of samples compared to the dimension of the solution space, indicating the network generalizes well.
Die-Stacked DRAM: Memory, Cache, or MemCache?

Die-stacked DRAM is a promising solution for satisfying the ever-increasing memory bandwidth requirements of multi-core processors. Manufacturing technology has enabled stacking several gigabytes of DRAM modules on the active die, thereby providing orders of magnitude higher bandwidth as compared to the conventional DIMM-based DDR memories. Nevertheless, die-stacked DRAM, due to its limited capacity, cannot accommodate entire datasets of modern big-data applications. Therefore, prior proposals use it either as a sizable memory-side cache or as a part of the software-visible main memory. Cache designs can adapt themselves to the dynamic variations of applications but suffer from the tag storage/latency/bandwidth overhead. On the other hand, memory designs eliminate the need for tags, and hence, provide efficient access to data, but are unable to capture the dynamic behaviors of applications due to their static nature. In this work, we make a case for using the die-stacked DRAM partly as main memory and partly as a cache. We observe that in modern big-data applications there are many hot pages with a large number of accesses. Based on this observation, we propose to use a portion of the die-stacked DRAM as main memory to host hot pages, enabling serving a significant number of the accesses from the high-bandwidth DRAM without the overhead of tag-checking, and manage the rest of the DRAM as a cache, for capturing the dynamic behavior of applications. In this proposal, a software procedure pre-processes the application and determines hot pages, then asks the OS to map them to the memory portion of the die-stacked DRAM. The cache portion of the die-stacked DRAM is managed by hardware, caching data allocated in the off-chip memory.
PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes

The transcriptional coactivators peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1α or PGC-1β overexpression in C2C12 myotubes increased protein synthesis and myotube diameter under basal conditions and attenuated the loss in protein synthesis following the treatment with the catabolic agent, dexamethasone. To investigate whether PGC-1α or PGC-1β signal through the Akt/mTOR pathway to increase protein synthesis, treatment with the PI3K and mTOR inhibitors, LY294002 and rapamycin, respectively, was undertaken but found unable to block PGC-1α or PGC-1β’s promotion of protein synthesis. Furthermore, PGC-1α and PGC-1β decreased phosphorylation of Akt and the Akt/mTOR substrate, p70S6K. In contrast to Akt/mTOR inhibition, the suppression of ERRα, a major effector of PGC-1α and PGC-1β activity, attenuated the increase in protein synthesis and myotube diameter in the presence of PGC-1α or PGC-1β overexpression. To characterize further the biological processes occurring, gene set enrichment analysis of genes commonly regulated by both PGC-1α and PGC-1β was performed following a microarray screen. Genes were found enriched in metabolic and mitochondrial oxidative processes, in addition to protein translation and muscle development categories. This suggests concurrent responses involving both increased metabolism and myotube protein synthesis. Finally, based on their known function or unbiased identification through statistical selection, two sets of genes were investigated in a human exercise model of stimulated protein synthesis to characterize further the genes influenced by PGC-1α and PGC-1β during physiological adaptive changes in skeletal muscle.
HERV-E expression in peripheral mononuclear cells of patient with Psoriasis.

BACKGROUND Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. Possible triggers for psoriasis have been attributed to drugs or pathogens such as bacteria and possibly virus. Human endogenous retroviruses (HERVs) might play a role in triggering these anti-viral immune responses, since the role of HERVs in the pathogenesis of autoimmune diseases has generated considerable interest. Some studies have also reported an association of HERV-E and psoriasis. None of them investigate the HERV-E expression in peripheral blood of psoriasis. All these considerations have prompted us to perform a survey for HERV-E expression in PBMC from psoriatic patients. METHODS Peripheral blood mononuclear cells from 69 psoriatic patients were analyzed. Total RNA was extracted and amplified with reverse transcription polymerase chain reaction. Results were compared with those obtained in a cohort of 20 healthy donors. RESULTS HERV E was expressed in all samples analyzed but the level of expression was much lower in the psoriasis that in HC p<0.0001. CONCLUSIONS The reasons for the unexpected, low levels of HERV expression in psoriatic patients are unclear and might be in part a consequence of anti-viral defense mechanisms.
Determination of the water gap and the germination ecology of Adenanthera pavonina (Fabaceae, Mimosoideae); the adaptive role of physical dormancy in mimetic seeds

Abstract Dormancy caused by impermeable seed coats, i.e. physical dormancy (PY), regulates the timing of seed germination in species of several genera belonging to 18 angiosperm families. Physical dormancy also occurs in some mimetic species whose seeds mimic brightly coloured, fleshy fruits or arilled seeds. However, the conditions that break dormancy, as well as the location of water gaps in mimetic seeds, remain unclear. Here, we investigated the adaptive role of impermeable coats in the mimetic seeds of Adenanthera pavonina (Fabaceae: Mimosoideae). Specifically, we explored: (i) the conditions that break PY; (ii) the location of the primary water gap that forms during dormancy break; and (iii) the effect of seasonal temperature regimes on seed germination. Seeds were subjected to hot-water treatment, rapid temperature fluctuations and storage at temperatures mimicking summer and autumn conditions. Seed coat anatomy and water-gap regions were characterized using scanning electron microscopy (SEM) and light microscopy. Seeds were artificially buried in the field at 3 and 7 cm depths and exhumed every 6 months for 2 years to monitor germination. Adenanthera pavonina had impermeable seed coats, and thus PY. Seeds treated with hot water and exposed to summer–autumn temperature regimes broke dormancy. Water entered only through the lens (Type-II simple) due to dislodgement of the palisade layer. Seeds buried at 3 cm depth had significantly higher germination than those buried at 7 cm depth, with germination primarily occurring in autumn. Seeds required high summer temperatures followed by moderate autumn temperatures to become permeable to water and germinate in the field during the wet season. We conclude that the impermeable seed coat of A. pavonina is an adaptation that synchronizes germination with the growing season.
Comparative evaluation of two toric intraocular lenses for correcting astigmatism in patients undergoing phacoemulsification

Purpose: To compare the efficacy of AT-TORBI plate haptic toric intraocular lens (IOL) (Carl Zeiss Meditec AG, Jena, Germany) and AcrySof loop haptic toric IOL (Alcon Laboratories, Inc., Fort Worth, TX, USA) for correcting preexisting astigmatism of ≥1 diopters (D) in patients undergoing phacoemulsification and to compare the rotational stability of these two toric IOLs. Methods: In this prospective randomized controlled trial. Forty-two eyes of 42 cataract patients with preexisting astigmatism of 1 D or more were randomized to receive plate haptic toric (AT TORBI) or loop haptic toric (AcrySof) IOLs, with 21 in each group. Postoperative evaluation was done at day 1, 1 week, 1 month, and 3 months. Uncorrected distance visual acuity (UDVA), best corrected visual acuity (VA), and IOL position were noted in both the groups. Results: At 3 months postoperatively, the mean log MAR UDVA was 0.23 ± 0.20 and 0.20 ± 0.13 in Groups I and II, respectively (P = 0.7), the mean residual cylindrical refractive error in plate haptic toric group was 0.40 ± 0.31 D and in loop haptic group was 0.45 ± 0.33 D (P = 0.64). The mean IOL rotation at 3 months follow-up in plate haptic group was found to be 3.52 ± 3.84° and in loop haptic group was 2.05 ± 2.56° (P = 0.25). Conclusion: Both types of toric IOLs were equally efficacious for attaining good uncorrected VA and correcting preexisting astigmatism between 1–5 D. Both of them were rotationally stable at 3 months follow-up.
Propensity score matching comparison of laparoscopic versus open surgery for rectal cancer in a middle-income country: short-term outcomes and cost analysis

Background Laparoscopic surgery for rectal cancer is associated with improved postoperative outcomes compared to open surgery; however, economic studies have yielded contradictory results. The aim of this study was to compare the clinical and economic outcomes of laparoscopic versus open surgery for patients with rectal cancer. Methods Propensity score matching analysis was performed in a retrospective cohort of patients who underwent elective low anterior resection for rectal cancer treatment by laparoscopic and open surgery in a single Brazilian cancer center. Matched covariates included age, gender, body mass index, pTNM stage, American Society of Anesthesiologists score, type of anesthesia, neoadjuvant chemoradiotherapy, and interval between neoadjuvant chemoradiotherapy and index surgery. The clinical and economic outcomes were evaluated. The follow-up period was within 30 days of the index procedure. The clinical outcomes were reoperation, postoperative complications, operative time, length of stay in the intensive care unit, and postoperative hospital stay. For economic outcomes, a cost analysis was used to compare the costs. Results Initially, 220 patients were evaluated. After propensity score matching, 100 patients were included in the analysis (50 patients in the open surgery group and 50 patients in the laparoscopic surgery group). There were no differences in patients’ baseline characteristics. Operative time was longer for laparoscopic surgery (247 minutes vs 285 minutes, P=0.006). There were no significant differences in other clinical outcomes. The hospital costs were similar between the two groups (Brazilian reais 21,233.15 vs Brazilian reais 21,529.28, P=0.115), although the intraoperative costs were higher for laparoscopic surgery, mainly owing to the surgical devices and the theater-related costs. The postoperative costs were lower for laparoscopic surgery, owing to lower intensive care unit, ward, and reoperation costs. Conclusion Laparoscopic surgery for rectal cancer is not costlier than open surgery from the health care provider’s perspective, since the intraoperative costs were offset by lower postoperative costs. Open surgery tends to have a longer length of stay.
The Subprimary Range of Firing Is Present in Both Cat and Mouse Spinal Motoneurons and Its Relationship to Force Development Is Similar for the Two Species

In the motor system, force gradation is achieved by recruitment of motoneurons and rate modulation of their firing frequency. Classical experiments investigating the relationship between injected current to the soma during intracellular recording and the firing frequency (the I–f relation) in cat spinal motoneurons identified two clear ranges: a primary range and a secondary range. Recent work in mice, however, has identified an additional range proposed to be exclusive to rodents, the subprimary range (SPR), due to the presence of mixed mode oscillations of the membrane potential. Surprisingly, fully summated tetanic contractions occurred in mice during SPR frequencies. With the mouse now one of the most popular models to investigate motor control, it is crucial that such discrepancies between observations in mice and basic principles that have been widely accepted in larger animals are resolved. To do this, we have reinvestigated the I–f relation using ramp current injections in spinal motoneurons in both barbiturate-anesthetized and decerebrate (nonanesthetized) cats and mice. We demonstrate the presence of the SPR and mixed mode oscillations in both species and show that the SPR is enhanced by barbiturate anesthetics. Our measurements of the I–f relation in both cats and mice support the classical opinion that firing frequencies in the higher end of the primary range are necessary to obtain a full summation. By systematically varying the leg oil pool temperature (from 37°C to room temperature), we found that only at lower temperatures can maximal summation occur at SPR frequencies due to prolongation of individual muscle twitches. SIGNIFICANCE STATEMENT This work investigates recent revelations that mouse motoneurons behave in a fundamentally different way from motoneurons of larger animals with respect to the importance of rate modulation of motoneuron firing for force gradation. The current study systematically addresses the proposed discrepancies between mice and larger species (cats) and demonstrates that mouse motoneurons, in fact, use rate modulation as a mechanism of force modulation in a similar manner to the classical descriptions in larger animals.