Miracle-dz/UniFAR-FTUs huggingface dataset:
The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor growth, and chemosensitivity under hypoxic conditions

Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin (mTOR), a central promotor of cell growth and proliferation. The protein product of the TSC1 gene, hamartin (referred to as TSC1) is known to interact with Polo-like kinase 1 (Plk1) in a cell cycle regulated, phosphorylation-dependent manner. We hypothesized that the p53 target gene, Plk2, is a tumor suppressor, mediating its tumor suppressor function through interactions with TSC1 that facilitate TSC1/2 restraint of mTOR under hypoxic stress. We found that human lung tumor cells deficient in Plk2 grew larger than control tumors, and that Plk2 interacts with endogenous TSC1 protein. Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins. TSC1 levels were elevated in response to Adriamycin and cells transiently over-expressing Plk2 demonstrated decreased phosphorylation of the downstream target of mTOR, ribosomal protein p70S6 kinase during hypoxia. Plk2 levels were inversely correlated with cytoplasmic p70S6K phosphorylation. Plk2 levels did not increase in response to DNA damage (Adriamycin, CPT-11) when HCT 116 and H460 cells were exposed to hypoxia. TSC1-deficient mouse embryonic fibroblasts with TSC1 added back demonstrated decreased S6K phosphorylation, which was further decreased when Plk2 was transiently over-expressed. Interestingly, under normoxia, Plk2 deficient tumor cells demonstrated increased apoptosis in response to various chemotherapeutic agents including CPT-11 but increased resistance to apoptotic death after CPT-11 treatment under hypoxia, and tumor xenografts comprised of these Plk2-deficient cells were resistant to CPT-11. Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy.
Correlation of P16 (Ink4a) and CK17 to HPV (16E6+18E6) in Premalignant and Malignant Lesions of Uterine Cervix: A Clinicopathologic Study

Background: This research was accomplished to evaluate the IHC expression of p16 (ink4a) and CK17 in low grade cervical intraepithelial lesions (LSIL), high grade cervical intraepithelial lesions (HSIL) and invasive cervical carcinomas and to assess their correlation to HPV (16E6+18E6). Methods: The study included (127) formalin-fixed paraffin-embedded cervical biopsies; of which 22 cases were chronic cervicitis, 24 cases were LSIL, 28 cases were HSIL and 53 cases were invasive cervical carcinomas. Sections were immunohistochemically stained for p16 (ink4a), CK17 and HPV (16E6+18E6). Results: The study established a highly significant increase in IHC of expression of p16 (ink4a), CK17 and HPV (16E6+18E6) from LSIL through HSIL to invasive carcinomas (P-value˂0.001). There was non-significant association between IHC expression of all makers with age of patients; types, grade and stage of cervical carcinomas (P-value˃0.05). HPV (16E6+18E6) revealed a significantly positive correlation with p16 (ink4a) (P-value˂0.05) and a non- significant correlation with CK17 (P-value˃0.05); in LSIL, HSIL and invasive carcinoma cases. Conclusion: p16 (ink4a) expression directly reflects infection with high risk HPV in cervical lesions and can add a significant diagnostic accuracy in the evaluation of CIN. CK 17 is a good marker of malignant transformation, with increasing in its expression according to the severity of cervical lesions; however, it is not related to HPV infection. Both markers are not related to prognostic variables of patients with cervical carcinoma.
The influence of social category cues on the happy categorisation advantage depends on expression valence

ABSTRACT Facial race and sex cues can influence the magnitude of the happy categorisation advantage. It has been proposed that implicit race or sex based evaluations drive this influence. Within this account a uniform influence of social category cues on the happy categorisation advantage should be observed for all negative expressions. Support has been shown with angry and sad expressions but evidence to the contrary has been found for fearful expressions. To determine the generality of the evaluative congruence account, participants categorised happiness with either sadness, fear, or surprise displayed on White male as well as White female, Black male, or Black female faces across three experiments. Faster categorisation of happy than negative expressions was observed for female faces when presented among White male faces, and for White male faces when presented among Black male faces. These results support the evaluative congruence account when both positive and negative expressions are presented.
Covered interest parity: The untestable hypothesis

ABSTRACT Although post Keynesian economists advocate the realistic bankers’ view of the forward exchange rate, neoclassical economists formulate (CIP) as a testable hypothesis. In reality, CIP represents a formula used by bankers to calculate the forward rates they quote to their customers. This article provides arguments for the post Keynesian view of the forward exchange rate and suggests that CIP is not a theory, that it is a microeconomic relation, and that it is a hedging rather than an arbitrage condition. An empirical illustration shows that deviations from CIP are observed whenever published data are used, but these deviations disappear when transaction data are used instead. It is concluded that CIP is an untestable hypothesis.
Association of C-Reactive Protein With Reduced Forced Vital Capacity in a Nonsmoking U.S. Population With Metabolic Syndrome and Diabetes

OBJECTIVE—A relationship between inflammation, measured by C-reactive protein (CRP), and forced vital capacity (FVC) in diabetes or metabolic syndrome (MetS) has not been established. We investigated whether high CRP is related to reduced FVC in MetS and diabetes. RESEARCH DESIGN AND METHODS—We examined the association of MetS/diabetes and CRP (normal ≤3 mg/l, high >3 mg/l) with predicted FVC in 4,272 nonsmoking U.S. adults aged 18–79 years without lung disease in the Third National Health and Nutrition Examination Survey. Logistic regression examined odds of FVC <80% by CRP and MetS/diabetes. RESULTS—Mean FVC in individuals with MetS and high CRP (95.7%) and those with diabetes and high CRP (93.7%) was lower than in those with no MetS/diabetes and normal CRP (101.7%) (P < 0.01) and was lower in those with MetS and high CRP (95.7%) than in those with MetS and normal CRP (98.5%) (P < 0.01). The odds ratio (95% CI) of FVC <80% was highest in individuals with MetS and high CRP (odds ratio 4.26 [95% CI 2.08–8.73], P < 0.01) compared with those with no MetS/diabetes and normal CRP. CONCLUSIONS—Elevated CRP is associated with lower FVC in people with MetS.
Mechanistic Dissection of the Enzyme Complexes Involved in Biosynthesis of Lacticin 3147 and Nisin

ABSTRACT The thioether rings in the lantibiotics lacticin 3147 and nisin are posttranslationally introduced by dehydration of serines and threonines, followed by coupling of these dehydrated residues to cysteines. The prepeptides of the two-component lantibiotic lacticin 3147, LtnA1 and LtnA2, are dehydrated and cyclized by two corresponding bifunctional enzymes, LtnM1 and LtnM2, and are subsequently processed and exported via one bifunctional enzyme, LtnT. In the nisin synthetase complex, the enzymes NisB, NisC, NisT, and NisP dehydrate, cyclize, export, and process prenisin, respectively. Here, we demonstrate that the combination of LtnM2 and LtnT can modify, process, and transport peptides entirely different from LtnA2 and that LtnT can process and transport unmodified LtnA2 and unrelated peptides. Furthermore, we demonstrate a higher extent of NisB-mediated dehydration in the absence of thioether rings. Thioether rings apparently inhibited dehydration, which implies alternating actions of NisB and NisC. Furthermore, certain (but not all) NisC-cyclized peptides were exported with higher efficiency as a result of their conformation. Taken together, these data provide further insight into the applicability of Lactococcus lactis strains containing lantibiotic enzymes for the design and production of modified peptides.
Uptake of tracer by the epiplexus cells via the choroid plexus epithelium following an intravenous or intraperitoneal injection of horseradish peroxidase in rats.

Rapid passage of horseradish peroxidase (HRP) from the blood circulation to the cerebrospinal fluid was demonstrated in postnatal rats. At 30 min-1 h after an intravenous (i.v.) injection of HRP, the extravasated tracer from the blood vessels entered the connective tissue of the choroid plexus to reach the epithelial intercellular spaces where it was retarded by the apical tight junctions. The HRP which accumulated in widened intercellular spaces was readily endocytosed by the epithelial cells, notably at their lateral surfaces. This was especially pronounced 3 h after the injection. The endocytosed HRP was either routed to lysosomes or discharged apically by exocytosis into the CSF via membrane-bound vesicles by the epithelial cells. After longer survival periods, i.e. 6 h after injection, the intercellular spaces were relatively clear of tracer. HRP-labelled vacuoles or vesicles had diminished with a concomitant increase in the number of lysosomes containing HRP reaction product. In the course of HRP injection, the epiplexus cells residing on the choroid epithelium progressively accumulated HRP by endocytosis so that in rats killed 6 h after injection, the cells were heavily loaded with HRP incorporated into massive lysosomes. The labelling pattern of epithelial and epiplexus cells in rats injected intraperitoneally followed that observed in those receiving i.v. injections. These results suggest that the epiplexus cells together with lysosomal activity by the choroid epithelial cells serve as a protective line of defence for the blood-CSF barrier which appears to be inefficient.
A Taxonomy of Different Forms of Visual Motion Detection and Their Underlying Neural Mechanisms

A simple taxonomy of different forms of visual motion is presented to show that there may be a hierarchical system of processing of visual motion in the brain, and that this is first split into self-produced motion and object motion, and then further into various forms of animate and inanimate motion patterns. Further refinement results in specific mechanisms which stem from specific demands of an animal’s life-style and ecological niche. Examples are presented of the underlying neural mechanisms for some of these different classes of visual motion processing, such as simple object motion, looming and time to collision, and stereopsis from the object motion processing subsystem. In contrast, other examples of the neural mechanisms from the self-produced motion system include simple canonical flow field analysis, translation and rotation for guiding action in 3D space, and motion parallax for depth perception. The taxonomy thus provides a framework that may guide future research on how the brain detects and processes other dynamic visual patterns.
Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans.

The increase in interstitial potassium (K+) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K+ in exercise hyperemia, we perfused skeletal muscle with K+ before contractions, such that the effect of any endogenously-released K+ would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF) (Doppler ultrasound) and forearm vascular conductance (FVC) (FBF/mean arterial pressure) during 4 min of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions, 2) infusion of KCl before the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly before the onset of exercise (control: 39 ± 6 vs. KCl: 81 ± 12 and SNP: 82 ± 13 ml·min-1·100 mmHg-1; both P < 0.05 vs. control). Infusion of KCl at rest diminished the hyperemic (ΔFBF) and vasodilatory (ΔFVC) response to subsequent exercise by 22 ± 5% and 30 ± 5%, respectively (both P < 0.05 vs. control), whereas SNP did not affect the change in FBF ( P = 0.74 vs. control) or FVC ( P = 0.61 vs. control) from rest to steady-state exercise. These findings implicate the K+ ion as an essential vasodilator substance contributing to exercise hyperemia in humans. NEW & NOTEWORTHY Our findings support a significant and obligatory role for potassium signaling in the local vasodilatory and hyperemic response to exercise in humans.
Olefin cis-dihydroxylation versus epoxidation by non-heme iron catalysts: two faces of an Fe(III)-OOH coin.

The oxygenation of carbon-carbon double bonds by iron enzymes generally results in the formation of epoxides, except in the case of the Rieske dioxygenases, where cis-diols are produced. Herein we report a systematic study of olefin oxidations with H(2)O(2) catalyzed by a group of non-heme iron complexes, i.e., [Fe(II)(BPMEN)(CH(3)CN)(2)](2+) (1, BPMEN = N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)-1,2-diaminoethane) and [Fe(II)(TPA)(CH(3)CN)(2)](2+) (4, TPA = tris(2-pyridylmethyl)amine) and their 6- and 5-methyl-substituted derivatives. We demonstrate that olefin epoxidation and cis-dihydroxylation are different facets of the reactivity of a common Fe(III)-OOH intermediate, whose spin state can be modulated by the electronic and steric properties of the ligand environment. Highly stereoselective epoxidation is favored by catalysts with no more than one 6-methyl substituent, which give rise to low-spin Fe(III)-OOH species (category A). On the other hand, cis-dihydroxylation is favored by catalysts with more than one 6-methyl substituent, which afford high-spin Fe(III)-OOH species (category B). For catalysts in category A, both the epoxide and the cis-diol product incorporate (18)O from H(2)(18)O, results that implicate a cis-H(18)O-Fe(V)=O species derived from O-O bond heterolysis of a cis-H(2)(18)O-Fe(III)-OOH intermediate. In contrast, catalysts in category B incorporate both oxygen atoms from H(2)(18)O(2) into the dominant cis-diol product, via a putative Fe(III)-eta(2)-OOH species. Thus, a key feature of the catalysts in this family is the availability of two cis labile sites, required for peroxide activation. The olefin epoxidation and cis-dihydroxylation studies described here not only corroborate the mechanistic scheme derived from our earlier studies on alkane hydroxylation by this same family of catalysts (Chen, K.; Que, L, Jr. J. Am. Chem. Soc. 2001, 123, 6327) but also further enhance its credibility. Taken together, these reactions demonstrate the catalytic versatility of these complexes and provide a rationale for Nature's choice of ligand environments in biocatalysts that carry out olefin oxidations.
Exploring Employee Interactions and Quality of Contributions in Intra‐Organisational Innovation Platforms

This study builds on the innovation management and organizational knowledge networks to examine the user interactions in an intra&#8208;organizational innovation platform of a Norwegian telecommunications operator, as well as the influence of user interactions on idea development. Although current studies mainly focus on user interactions and idea quality in innovation processes, little attention has been paid to the layered nature of user interactions that impact on idea development. Data from an intra&#8208;organizational innovation platform, called Explorathon, was used in an exploratory study, with a mixed&#8208;methods approach. For 10 days, 3200 employees posted 390 ideas, with 1435 comments. Results show that employees communicated through the innovation platform with 11 interaction types, eight contribution types and three collaboration types. The findings demonstrate that diverse platform interactions coexist and have a diverse impact on ideas. The authors suggest three types of contribution qualities&#8212;passive, efficient and balanced&#8212;that reflect the degree of meaningful interactions around an idea. The contribution qualities are only indicative of the content of interactions and they complement other evaluation metrics of the innovation platform. The findings also suggest that the user roles of idea contributors and platform moderators or facilitators are significant in maintaining interactions and weighted contributions over time. The study has implications both for research and practice.
Ice Core Evidence for Extensive Melting of the Greenland Ice Sheet in the Last Interglacial

Evidence from ice at the bottom of ice cores from the Canadian Arctic Islands and Camp Century and Dye-3 in Greenland suggests that the Greenland ice sheet melted extensively or completely during the last interglacial period more than 100 ka (thousand years ago), in contrast to earlier interpretations. The presence of dirt particles in the basal ice has previously been thought to indicate that the base of the ice sheets had melted and that the evidence for the time of original growth of these ice masses had been destroyed. However, the particles most likely blew onto the ice when the dimensions of the ice caps and ice sheets were much smaller. Ice texture, gas content, and other evidence also suggest that the basal ice at each drill site is superimposed ice, a type of ice typical of the early growth stages of an ice cap or ice sheet. If the present-day ice masses began their growth during the last interglacial, the ice sheet from the earlier (Illinoian) glacial period must have competely or largely melted during the early part of the same interglacial period. If such melting did occur, the 6-meter higher-than-present sea level during the Sangamon cannot be attributed to disintegration of the West Antarctic ice sheet, as has been suggested.
Changing patterns of drug use among US military recruits before and after enlistment.

OBJECTIVES The US armed forces adopted "zero tolerance" policies concerning illicit drug use in 1980 and later developed policies to discourage tobacco and alcohol abuse. This article examines drug use among young active-duty recruits both before and after enlistment, compared with nonmilitary age-mates, and documents historical shifts in such drug use across 2 decades. METHODS Analyses employed longitudinal panel data from 20 nationally representative samples of high school seniors (cohorts of 1976-1995), each surveyed just before graduation and again within 2 years. Separate analyses for men (n = 12,082) and women (n = 15,345) contrasted those who entered military service, college, and civilian employment. RESULTS Illicit drug use declined more among young military recruits than among their civilian counterparts. Analyses of male recruits at multiple time periods showed (1) declines in the prevalence of marijuana use and cocaine use after the initiation of routine military drug testing and (2) lower proportions of smokers of half a pack or more of cigarettes per day who entered service after the initiation of tobacco bans during basic training. CONCLUSIONS Recent military drug policies appear to deter illicit drug use among enlistees and discourage some smokers from enlisting.
Molecular basis of Mycoplasma surface antigenic variation: a novel set of divergent genes undergo spontaneous mutation of periodic coding regions and 5′ regulatory sequences.

Antigenic diversity is generated in the wall‐less pathogen Mycoplasma hyorhinis by combinatorial expression and phase variation of multiple, size‐variant membrane surface lipoproteins (Vlps). The unusual structural basis for Vlp variation was revealed in a cluster of related but divergent vlp genes, vlpA, vlpB and vlpC, which occur as single chromosomal copies. These encode conserved N‐terminal domains for membrane insertion and lipoprotein processing, but divergent external domains undergoing size variation by loss or gain of repetitive intragenic coding sequences while retaining a motif with distinctive charge distribution. Genetic analysis of phenotypically switched isogenic lineages representing ON or OFF expression states of Vlp products ruled out chromosomal rearrangement or frameshift mutations as mechanisms for Vlp phase variation. However, highly conserved vlp promoter regions contain a tract of contiguous A residues immediately upstream of the −10 box which is subject to frequent mutations altering its length in exact correspondence with the ON and OFF phase states of specific genes. This suggests a mechanism of transcriptional control regulating high frequency phase variation and random combinatorial expression of Vlps. The multiple levels of diversity embodied in the vlp gene cluster represents a novel adaptive capability particularly suited for this class of wall‐less microbe.
Comparative Evaluation of the Performance of the Abbott Real-Time Human Immunodeficiency Virus Type 1 (HIV-1) Assay for Measurement of HIV-1 Plasma Viral Load following Automated Specimen Preparation

ABSTRACT The performance of the new Abbott real-time human immunodeficiency virus type 1 (HIV-1) assay for HIV-1 RNA load determination in plasma was compared to that of the Abbott LCx HIV-1 RNA quantitative assay following automated RNA isolation by the Abbott m1000 extractor. The measured viral loads of 89 clinical specimens differed by mean 0.19 log10 copies/ml (95% confidence interval, 0.12 to 0.26 log10 copies/ml). Although the difference in viral load determinations was positively skewed in favor of the LCx assay, it did not reach statistical significance (P = 0.42). Results were linearly associated (R2 = 0.94) and strongly correlated (R = 0.96). Good performance was observed with HIV-1 subtypes other than B and circulating recombinant forms, although results obtained with two subtype G specimens and one H specimen showed a more substantial difference.
A FOLLOW‐UP STUDY OF INFANTS WITH ADVERSE REACTIONS TO COW'S MILK I. Serum IgE, Skin Test Reactions and RAST in Relation to Clinical Course

Abstract. 47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST‐titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow‐up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.