Miracle-dz/UniFAR-FTUs huggingface dataset:
Botulinum neurotoxin type D enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates

Multi‐domain bacterial protein toxins are being explored as potential carriers for targeted delivery of biomolecules. Previous approaches employing isolated receptor binding subunits disallow entry into the cytosol. Strategies in which catalytic domains are replaced with cargo molecules are presumably inefficient due to co‐operation of domains during the endosomal translocation step. Here, we characterize a novel transport vehicle in which cargo proteins are attached to the amino terminus of the full‐length botulinum neurotoxin type D (BoNT/D). The intrinsic enzymatic activity of the neurotoxin allowed quantification of the efficacy of cargo delivery to the cytosol. Dihydrofolate reductase and BoNT type A (BoNT/A) light chain (LC) were efficiently conveyed into the cytosol, whereas attachment of firefly luciferase or green fluorescent protein drastically reduced the toxicity. Luciferase and BoNT/A LC retained their catalytic activity as evidenced by luciferin conversion or SNAP‐25 hydrolysis in the cytosol of synaptosomes, respectively. Conformationally stabilized dihydrofolate reductase as cargo considerably decreased the toxicity indicative for the requirement of partial unfolding of cargo protein and catalytic domain as prerequisite for efficient translocation across the endosomal membrane. Thus, enzymatically inactive clostridial neurotoxins may serve as effective, safe carriers for delivering proteins in functionally active form to the cytosol of neurones.
Venturing into Foreign Markets: The Case of the Small Service Firm

The study contrasts foreign market entry behavior of small and large service firms. The sample consisted of 141 firms of which 54 were small firms and 87 were larger firms. The study provides empirical evidence that the behavior of small firms differs from that of larger firms mainly in service industries characterized by higher capital intensity. It also suggests that at lower levels of capital intensity, small firm behavior may resemble that of larger firms. More specifically, In industries characterized by lower levels of capital Intensity, small service firms are as likely as their larger counterparts to enter culturally distant markets and to choose foreign direct Investment (FDI) modes of entry. But, at higher levels of capital Intensity, small service forms are less likely than larger ones to enter culturally distant markets, and to choose FDI modes of entry.
Perceived differences in social status between speaker and listener affect the speaker's vocal characteristics

Non-verbal behaviours, including voice characteristics during speech, are an important way to communicate social status. Research suggests that individuals can obtain high social status through dominance (using force and intimidation) or through prestige (by being knowledgeable and skilful). However, little is known regarding differences in the vocal behaviour of men and women in response to dominant and prestigious individuals. Here, we tested within-subject differences in vocal parameters of interviewees during simulated job interviews with dominant, prestigious, and neutral employers (targets), while responding to questions which were classified as introductory, personal, and interpersonal. We found that vocal modulations were apparent between responses to the neutral and high-status targets, with participants, especially those who perceived themselves as low in dominance, increasing fundamental frequency (F0) in response to the dominant and prestigious targets relative to the neutral target. Self-perceived prestige, however, was less related to contextual vocal modulations than self-perceived dominance. Finally, we found that differences in the context of the interview questions participants were asked to respond to (introductory, personal, interpersonal), also affected their vocal parameters, being more prominent in responses to personal and interpersonal questions. Overall, our results suggest that people adjust their vocal parameters according to the perceived social status of the listener as well as their own self-perceived social status.
Birth Legacies, State Making, and War

International relations researchers study the interactions of states in the international system. Excluded from almost all such analyses is any consideration of how those states became members of the international system in the first place. State making researchers, in contrast, focus on the formation experiences of states. Drawing on insights from both approaches, we argue that states with positive birth legacies should be more successful at state making and achieve more favorable outcomes than states without positive birth legacies. As fighting and winning wars are a common pathway to political development, states with positive birth legacies should be more likely to participate in and win interstate and civil wars. Statistical analyses of all states in the international system from 1816 to 2002 support our expectations.
Ghost Numbers

We comment on a paper describing an algorithm for image set classification. Following the general practice in computer vision research, the performance of the algorithm was evaluated on benchmarks in order to support the claim of its advantage over other algorithms in the literature. We have examined the reported data of experiences on two datasets, and found that many numbers are not a possible answer regardless how the random partitions were selected and regardless how the algorithms performed in each partition. Our finding suggests that the experimental results in the paper (“Deep Reconstruction Models for Image Set Classification”, IEEE Trans. Pattern Analysis and Machine Intelligence, vol. 37, no. 4, pp. 713–727, April 2015) has serious flaws to the extent that all the experimental results should be re-examined.
Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease

Objective Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD) in hypertensive adults. Methods The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1) rapid decline in renal function and 2) annual rate of eGFR decline. Results The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57). However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95) was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL) levels. More importantly, there was an interaction between TBiL and smoking status on the primary outcome (P for interaction =0.013). Among ever smokers, TBiL levels had no significant effect on the primary outcome. However, among never smokers, higher TBiL levels were significantly associated with a lower risk of the primary outcome (tertile 3 vs 1–2; OR: 0.53, 95% CI: 0.36–0.78). Similar trends were observed for direct bilirubin and secondary outcomes. Conclusion Among hypertensive patients, bilirubin was inversely associated with the progression of CKD in never smokers, but not in ever smokers.
Thymus mastichina: Chemical Constituents and their Anti-Cancer Activity

The cytotoxicity-guided study of the dichloromethane and ethanol extracts of Thymus mastichna L. using the HCT colon cancer cell line allowed the identification of nine compounds, sakuranetin (1), sterubin (2), oleanolic acid (3), ursolic acid (4), lutein (5), β-sitosterol (6), rosmarinic acid (7), 6-hydroxyluteolin-7-O-β-glucopyranoside (8), and 6-hydroxyapigenin-7-O-β-glucopyranoside (9). All compounds were tested for their cytotoxicity against the HCT colon cancer cell line. Compound 4 showed cytotoxicity with GI50 value of 6.8 μg/mL. A fraction composed of a mixture (1:1) of triterpenoid acids 3 and 4 displayed improved cytotoxicity with a GI50 of 2.8 μg/mL suggesting a synergistic behavior. This is the first report on the chemical constituents of Thymus mastichna L. based on structural assignments by spectroscopic analysis. The presence of these constituents identified by colon cancer cytotoxicity-guided activity indicates that extracts of T. mastichna L. may have a protective effect against colon cancers.
Bone healing in rats submitted to weight-bearing and non-weight-bearing exercises.

BACKGROUND To investigate the effects of low-intensity exercise on bone healing during a short time. MATERIAL/METHODS We made a surgical 1-mm perforation in the upper third medial cortical of the right tibia of 45 male Wistar rats (3 months old; mean weight, 282+/-34 g). Animals were randomly assigned to a swimming exercise group (SWIM, n=15), a running exercise group (RUN, n=15), or a no exercise control group (CON, n=15). Treatment sessions (10 minutes/day, 5 days/week) were done for 7, 14, or 21 days. Tibias were removed for radiographic, morphometric, and stereologic analyses. Blood samples were obtained for biochemical analyses. RESULTS Serum phosphorus levels were higher in animals in the RUN group compared with animals in the SWIM group on the seventh day. On the 14th day, the tibias of the animals in the SWIM and RUN groups exhibited higher radiopacity in radiographic grades than animals in the CON group. No difference in collagen morphometry was verified. On the 21st day, serum alkaline phosphatase levels were higher in animals in the CON group than they were in the exercise groups, and animals in the SWIM and CON groups demonstrated an increase in newly formed bone in comparison to animals in the RUN group. CONCLUSIONS At the 14th day of treatment, weight-bearing exercise, assessed by radiography, was found to be beneficial for bone healing. Results at the 21st day of treatment further supported the benefits of non-weight-bearing exercises, showing that weight-bearing exercise may improve bone repair in rats.
Indwelling Catheterization in Caesarean Section: Time To Retire It!

BACKGROUND Routine placement of indwelling catheter preoperatively in Caesarean Section is being practiced without justified scientific evidence. AIM To evaluate the effect of routine indwelling catheterization on the postoperative ambulation, morbidity and hospital stay in women undergoing Caesarean section. SETTINGS AND DESIGN Case-Control study carried in a tertiary teaching hospital. MATERIALS AND METHODS This study was carried over 150 women undergoing primary Caesarean section without any medical complication or pre-existing Urinary Tract Infections (UTI). The subjects were randomly allocated to 2 groups i.e. Group 1(Non-Catheterized; NC) and Group 2 (Catheterized for 24 hours postoperatively; C). Parameters noted were; duration of surgery, time of ambulation, postoperative voiding discomfort {graded as - no, mild, moderate-severe, by Visual Analog Scoring (VAS)}, incidence of UTI, postoperative urinary retention, need of postoperative antibiotics and duration of hospital stay. STATISTICAL ANALYSIS Results were analysed using unpaired t-test. RESULTS There was no significant difference in duration of surgery and postoperative urinary retention in both groups. However, it was seen that non-catheterized patients had significantly earlier ambulation, shorter hospital stay, took less time for first voiding, lesser voiding discomfort, less incidence of UTI and lesser use of postoperative antibiotics. CONCLUSION The routine use of indwelling catheter in Caesarean section is unscientific and unnecessary. There should be selective rather than routine catheterization.
Microwave ablation at 915 MHz vs 2.45 GHz: A theoretical and experimental investigation.

PURPOSE The relationship between microwave ablation system operating frequency and ablation performance is not currently well understood. The objective of this study was to comparatively assess the differences in microwave ablation at 915 MHz and 2.45 GHz. METHODS Analytical expressions for electromagnetic radiation from point sources were used to compare power deposition at the two frequencies of interest. A 3D electromagnetic-thermal bioheat transfer solver was implemented with the finite element method to characterize power deposition and thermal ablation with asymmetrical insulated dipole antennas (single-antenna and dual-antenna synchronous arrays). Simulation results were validated against experiments in ex vivo tissue. RESULTS Theoretical, computational, and experimental results indicated greater power deposition and larger diameter ablation zones when using a single insulated microwave antenna at 2.45 GHz; experimentally, 32±4.1 mm and 36.3±1.0 mm for 5 and 10 min, respectively, at 2.45 GHz, compared to 24±1.7 mm and 29.5±0.6 mm at 915 MHz, with 30 W forward power at the antenna input port. In experiments, faster heating was observed at locations 5 mm (0.91 vs 0.49 °C/s) and 10 mm (0.28 vs 0.15 °C/s) from the antenna operating at 2.45 GHz. Larger ablation zones were observed with dual-antenna arrays at 2.45 GHz; however, the differences were less pronounced than for single antennas. CONCLUSIONS Single- and dual-antenna arrays systems operating at 2.45 GHz yield larger ablation zone due to greater power deposition in proximity to the antenna, as well as greater role of thermal conduction.
Study of mosaicism of Pyropia yezoensis

ABSTRACT Cytological observations and sequence analysis of the ribosomal intergenic spacer (IGS) were conducted on conchospores and thalli of Pyropia yezoensis from China. The complete progress of conchospore germination of P. yezoensis was observed, and a tracking study of P. yezoensis mosaics was conducted by microscope, our results showed that the thallus is haploid, with three chromosomes; and the conchocelis is diploid, with six chromosomes. Conchospore germination of P. yezoensis developed in a linear pattern, and cell divisions were not synchronous. The thallus of P. yezoensis was divided into ten parts in our study, IGS was used as a molecular marker to conduct a sequence analysis of different portions of a complete thallus (the reproductive region, nutrient region, and base). P. yezoensis is mosaic of different genetic material based on molecular level differences among the IGS sequences of the different parts of P. yezoensis. The thallus was homozygous; with either two or three mosaics. Chimerism of Pyropia was proven at both the morphological and the molecular level. The results of our study supported the dominant view that meiosis of Pyropia occurs during conchospore germination.
FOXO1 Regulates Dendritic Cell Activity through ICAM-1 and CCR7

The transcription factor FOXO1 regulates cell function and is expressed in dendritic cells (DCs). We investigated the role of FOXO1 in activating DCs to stimulate a lymphocyte response to bacteria. We show that bacteria induce FOXO1 nuclear localization through the MAPK pathway and demonstrate that FOXO1 is needed for DC activation of lymphocytes in vivo. This occurs through FOXO1 regulation of DC phagocytosis, chemotaxis, and DC–lymphocyte binding. FOXO1 induces DC activity by regulating ICAM-1 and CCR7. FOXO1 binds to the CCR7 and ICAM-1 promoters, stimulates CCR7 and ICAM-1 transcriptional activity, and regulates their expression. This is functionally important because transfection of DCs from FOXO1-deleted CD11c.Cre+FOXO1L/L mice with an ICAM-1–expressing plasmid rescues the negative effect of FOXO1 deletion on DC bacterial phagocytosis and chemotaxis. Rescue with both CCR7 and ICAM-1 reverses impaired DC homing to lymph nodes in vivo when FOXO1 is deleted. Moreover, Ab production following injection of bacteria is significantly reduced with lineage-specific FOXO1 ablation. Thus, FOXO1 coordinates upregulation of DC activity through key downstream target genes that are needed for DCs to stimulate T and B lymphocytes and generate an Ab defense to bacteria.
mRNA-Binding Protein ZFP36 Is Expressed in Atherosclerotic Lesions and Reduces Inflammation in Aortic Endothelial Cells

Objective—We studied the expression and function of an mRNA-binding protein, zinc finger protein-36 (ZFP36), in vascular endothelial cells in vivo and in vitro. We tested the hypotheses that ZFP36 regulates inflammation in vascular endothelial cells and that it functions through direct binding to target cytokine mRNAs. We also tested whether ZFP36 inhibits nuclear factor-&kgr;B–mediated transcriptional responses in vascular endothelial cells. Approach and Results—ZFP36 was minimally expressed in healthy aorta but was expressed in endothelial cells overlying atherosclerotic lesions in mice and humans. The protein was also expressed in macrophage foam cells of atherosclerosis. ZFP36 was expressed in human aortic endothelial cells in response to bacterial lipopolysaccharide, glucocorticoid, and forskolin, but not oxidized low-density lipoproteins or angiotensin II. Functional studies demonstrated that ZFP36 reduces the expression of inflammatory cytokines in target cells by 2 distinct mechanisms: ZFP36 inhibits nuclear factor-&kgr;B transcriptional activation and also binds to cytokine mRNAs, leading to reduced transcript stability. Conclusions—ZFP36 is expressed in vascular endothelial cells and macrophage foam cells where it inhibits the expression of proinflammatory mRNA transcripts. The anti-inflammatory effects of ZFP36 in endothelial cells occur via both transcriptional and posttranscriptional mechanisms. Our data suggest that enhancing vascular ZFP36 expression might reduce vascular inflammation.
Phenotype of dystrophinopathy in old MDX mice

Background: Mdx mutant mice, like patients with Duchenne Muscular Dystrophy (DMD), lack dystrophin, a subsarcolemmal protein, that results in myofiber necrosis. However young mdx mice, in contrast to DMD children, exhibit a successful muscle regeneration and not an extensive fibrosis.
Mindfulness Training for Social Service Providers in Hawaii: Context and Considerations

Abstract Few studies exploring outcomes for mindfulness training have specifically focused on social service providers such as case managers, juvenile justice (probation/parole) officers, family court liaisons, substance abuse and mental health counselors, and school behavioral health specialists, among others. This study examined whether social service professionals across various agencies in the state of Hawai‘i would be accepting of mindfulness-based training and practices, and explored their personal practice experiences. Participants (N = 97) received mindfulness skills training including mindful breathing, mindful walking, and the body scan. Through post-evaluation surveys, practice logs of homework practices, and reflections, they were then asked to reflect on their experiences with the practice and identify potential changes that they would attribute to mindfulness. Interpretative phenomenological and content analyses revealed that participants generally reported a high level of acceptance of the mindfulness training and practices but progress, continuity, and sustainability were slow. Findings provided some indications of mindfulness resulting in salutary effects for social service professionals, but the training structure was problematic. Future research needs to examine how institutional, cultural milieu facilitate or hinder opportunities for social service professionals to embody and embed mindfulness in daily life; this would require multimodal and qualitative methodologies that seek to highlight and understand the live experiences of social service providers.
Intratetrad mating, heterozygosity, and the maintenance of deleterious alleles in Microbotryum violaceum (=Ustilago violacea)

The mating system of Microbotryum violaceum was investigated in populations that are polymorphic for mating-type bias, where individuals produce viable haploids of only one of the two required mating types. The cause of mating-type bias was identified as deleterious recessive alleles linked to mating type. Maintenance of the deleterious alleles was promoted by early conjugation among products of single meioses, such that the duration of the free-living haploid stage is minimized. This development was also observed in nonbiased isolates. As a consequence, the mating system tends toward mating within the tetrad, which might be expected to reduce heterozygosity. However, complete centromere linkage of mating type ensures conjugation between first division meiotic products, such that mating in M. violaceum is analogous to forms of meiotic parthenogenesis with first division restitution (i.e. automixis with central fusion). This fungus was used to test the prediction that this mating system would maintain heterozygosity in regions of the genome linked to centromeres. Therefore, populations were screened for additional heterozygous lethal recessive alleles linked to centromeres, and several examples were found. Furthermore, the occurrence of intratetrad mating in M. violaceum provides an explanation for low variation among individuals within populations, inconsistent estimates of outcrossing rates, low levels of mating between tetrads of one diploid individual, and high frequencies of haplo-lethal alleles in natural populations.
Phosphorylation of Fli1 at Threonine 312 by Protein Kinase C δ Promotes Its Interaction with p300/CREB-Binding Protein-Associated Factor and Subsequent Acetylation in Response to Transforming Growth Factor β

ABSTRACT Previous studies have shown that transforming growth factor β (TGF-β)-induced collagen gene expression involves acetylation-dependent dissociation from the human α2(I) collagen (COL1A2) promoter of the transcriptional repressor Fli1. The goal of this study was to elucidate the regulatory steps preceding the acetylation of Fli1. We first showed that TGF-β induces Fli1 phosphorylation on a threonine residue(s). The major phosphorylation site was localized to threonine 312 located in the DNA binding domain of Fli1. Using several independent approaches, we demonstrated that Fli1 is directly phosphorylated by protein kinase C δ (PKC δ). Additional experiments showed that in response to TGF-β, PKC δ is recruited to the collagen promoter to phosphorylate Fli1 and that this step is a prerequisite for the subsequent interaction of Fli1 with p300/CREB-binding protein-associated factor (PCAF) and an acetylation event. The phosphorylation of endogenous Fli1 preceded its acetylation in response to TGF-β stimulation, and the blockade of PKC δ abrogated both the phosphorylation and acetylation of Fli1 in dermal fibroblasts. Promoter studies showed that a phosphorylation-deficient mutant of Fli1 exhibited an increased inhibitory effect on the COL1A2 gene, which could not be reversed by the forced expression of PCAF or PKC δ. These data strongly suggest that the phosphorylation-acetylation cascade triggered by PKC δ represents the primary mechanism whereby TGF-β regulates the transcriptional activity of Fli1 in the context of the collagen promoter.