Miracle-dz/UniFAR-FTUs huggingface dataset:
SQSTM1/p62-mediated autophagy compensates for loss of proteasome polyubiquitin recruiting capacity

ABSTRACT Protein homeostasis in eukaryotic cells is regulated by 2 highly conserved degradative pathways, the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Recent studies revealed a coordinated and complementary crosstalk between these systems that becomes critical under proteostatic stress. Under physiological conditions, however, the molecular crosstalk between these 2 pathways is still far from clear. Here we describe a cellular model of proteasomal substrate accumulation due to the combined knockdown of PSMD4/S5a and ADRM1, the 2 proteasomal ubiquitin receptors. This model reveals a compensatory autophagic pathway, mediated by a SQSTM1/p62-dependent clearance of accumulated polyubiquitinated proteins. In addition to mediating the sequestration of ubiquitinated cargos into phagophores, the precursors to autophagosomes, SQSTM1 is also important for polyubiquitinated aggregate formation upon proteasomal inhibition. Finally, we demonstrate that the concomitant stabilization of steady-state levels of ATF4, a rapidly degraded transcription factor, mediates SQSTM1 upregulation. These findings provide new insight into the molecular mechanisms by which selective autophagy is regulated in response to proteasomal overflow.
Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10–deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.
Effects of dietary supplementation of bacteriophages against enterotoxigenic Escherichia coli (ETEC) K88 on clinical symptoms of post‐weaning pigs challenged with the ETEC pathogen

The present study was performed to investigate the effects of dietary supplementation of bacteriophages (phages) against enterotoxigenic Escherichia coli (ETEC) K88 as a therapy against the ETEC infection in post-weaning pigs. Two groups of post-weaning pigs aged 35 days, eight animals per group, were challenged with 3.0 × 1010 colony forming units of ETEC K88, a third group given the vehicle. The unchallenged group and one challenged group were fed a basal nursery diet for 14 days while the remaining challenged group was fed the basal diet supplemented with 1.0 × 107 plaque forming units of the phage per kg. Average daily gain (ADG), goblet cell density and villous height:crypt depth (VH:CD) ratio in the intestine were less in the challenged group than in the unchallenged group within the animals fed the basal diet (p < 0.05); the reverse was true for rectal temperature, faecal consistency score (FCS), E. coli adhesion score (EAS) in the intestine, serum interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) concentrations and digesta pH in the stomach, caecum and colon. The ETEC infection symptom within the challenged animals was alleviated by the dietary phage supplementation (p < 0.05) in ADG, FCS, EAS in the jejunum, serum TNF-α concentration, digesta pH in the colon, goblet cell density in the ileum and colon and VH:CD ratio in the ileum. Moreover, the infection symptom tended to be alleviated (p < 0.10) by the phage supplementation in rectal temperature, EAS in the ileum and caecum, and VH:CD ratio in the duodenum and jejunum. However, EAS in the colon, digesta pH in the stomach and caecum, and goblet cell density in the jejunum did not change due to the dietary phage. Overall, results indicate that the phage therapy is effective for alleviation of acute ETEC K88 infection in post-weaning pigs.
Identifying the influence of gender on motivation and engagement levels in student physiotherapists

Abstract Background: There is an increasing focus in higher education on the role of learner characteristics and their influence on academic performance. Educators are interested in how students engage with learning activities as they progress through the curriculum. A previous study highlighted gender effects in academic performance in student physiotherapists, despite comparable entry scores. Aims: The aim of this study was to determine variation in student motivation and engagement, across the four year levels of the physiotherapy program at The University of Notre Dame Australia while considering gender and age. Methods: A cross-sectional design was adopted surveying 233 students utilising the Motivation and Engagement Scale – University/College (MES-UC), to review motivational thoughts and behaviours influencing learning. Results: Results identified gender effects with males having on average significantly lower scores for planning, task management and persistence; and higher scores for disengagement from their studies. Females displayed higher average scores for anxiety particularly in their first year and final clinical year. Results were consistent with gender effects noted in academic performance throughout the program for previous student cohorts. Conclusions: The application of the MES-UC early in course would highlight to educators the areas where intervention can be targeted. Early individualized intervention is recommended to address learner characteristics influencing performance.
Comparision between two stand-alone PV configurations: Series PVs versus series VSCs

In this paper, two standalone PV systems are compared. One of them has two series PVs that are connected to DC/DC and then DC/AC converters for feeding the AC load. The other configuration uses two separate PV and DC/DC converters, with series DC/AC converters on the AC load side. It is shown that the series inverter has advantages like improved harmonic condition, keeping both PVs in maximum power point, especially in shading condition. But, it has disadvantages like increasing the number of components and cost, decreasing reliability and unequal power absorption from each PV.
Estrogen contributes to non-pRb targeted HPV18 E7-caused cell proliferation and transformation

Almost all of cervical carcinoma arises as a result of persistent infection with high-risk human papillomaviruses (HPVs) where E7 oncogene plays an important role. In addition, estrogen is a confirmed cofactor in HPV related cervical carcinoma working synergistically with E7. There are two pathways involved in the E7 carcinogenesis of cervical cancer, the pRb-dependent and pRb-independent pathway. In this study we analyzed that whether estrogen contributes to high-risk HPV E7 in cervical carcinogenesis via pRb-independent pathway or not. E7△RB, which can not bind to and degrade pRb protein, hence no transformation ability, worked synergistically with estrogen in cell proliferation and transformation. Estrogen combined with PTD-HPV18E7△RB enhanced cell proliferation rate, induced genomic instability, including abnormal centrosome duplication and chromosomal instability, and exhibited malignant transformation with anchorage-independent growth. We also observed that, PTD-HPV18E7 △RB can interact with c-Jun and c-Myc proteins, but this interaction was limited to the estrogen-treated cells where c-Jun and c-Myc were expressed highly and no such interaction was observed in estrogen-untreated cells where c-Jun and c-Myc expression levels were low. In conclusion, estrogen can cooperate with E7 through a pRB-independent manner in cervical carcinogenesis. The functional interaction between E7 and c-Jun or between E7 and c-Myc could only be triggered when the c-Jun or c-Myc expression level reaches a certain threshold.
Communication between the Maternal Testa and the Embryo and/or Endosperm Affect Testa Attributes in Tomato1[w]

Two tomato (Lycopersicon esculentum) mutants with dark testae displaying poor germination rate and percentage on both water and 100 μm gibberellin4 + 7 were recovered. The mutants were allelic (black seed1-1; bks1-1 and bks1-2), inherited in Mendelian fashion as a recessive gene residing on chromosome 11. They are not allelic to bs (brown seed) -1, -2, or -4, which impair seed germination and possess dark testae. The bks/bs mutants accumulated dark pigment in the cell layers of the testa above the endothelium, which itself accumulated proanthocyanidins similar to wild type. The poor germination performance of bks mutant seeds was because of impediment of the mutant testae to radicle egress. Imbibition on gibberellin4 + 7 did not ameliorate germination percentage or rate. The toughening of the bks testa and associated poor germination were partially overcome when seeds were not dried before germination or were dried under N2. The seeds of the bks mutant have elevated activity of at least one enzyme responsible for the detoxification of reactive oxygen species. The bks mutant is epistatic to 12 anthocyaninless mutants of tomato. Bio- and physicochemical analysis of the bks testa determined that it accumulated a melanic substance. Inheritance of bks/bs mutations contrasts with that of the anthocyaninless mutants, which are inherited according to the genotype of the maternally derived testa. This suggests that the testa manufactures components before its demise that can maximize testa strength, whereas the endosperm/embryo produces factors that are conveyed to the testa, mitigating this process.
A Continuously Tunable Ka-Band Gyrotron

An experimental study was carried out to test the concept of using a gyrotron with a tapered circuit in a uniform magnetic field as a high-power tunable source of millimeter-wave radiation. It was demonstrated that the device can be used as either an oscillator or an amplifier with the operating frequency tunable by varying the magnetic field. In the oscillator mode, the tube produced a peak output power of 500-750 W with the frequency continuously tunable from 30 to 39 GHz. As an amplifier mode, the tube demonstrated an electronic gain of ~23 dB at a magnetically tunable center frequency with an instantaneous bandwidth of ~5 percent. The stability characteristics of the amplifier were also investigated.
Influence of L–threonine supplementation on goblet cell numbers, histological structure and antioxidant enzyme activities of laying hens reared in a hot and humid climate

1. A previous experiment in our laboratory found that L-threonine supplementation at 0·2 and 0·3% increased egg production and the concentration of serum IgG, respectively. The objective of this current trial was to determine if both supplementation levels can positively influence histological structure, goblet cell numbers, or antioxidant enzyme activities. 2. Babcock Brown layers (n = 576), 40 weeks of age, were allocated to three treatment groups, each of which included 6 replicates of 32 hens. Each group received the same basal diet formulated with maize, peanut meal and crystalline amino acids. L-threonine was added to the basal diet at 0 (control), 0·2, and 0·3%, respectively for 8 weeks. Chemical analysis of the diets for threonine values were 0·47, 0·66 and 0·74 %, respectively. 3. The numbers of goblet cells did not change due to L-threonine supplementation. Also, L-threonine had no affect on the villus height and mucosal thickness. No differences were found due to treatments among groups in the activity of alkaline phosphatase (ALP) in jejunum or ileum. L-threonine supplementation at 0·2% maximised the concentration of superoxide dismutases (SOD) in both serum and liver. 4. In conclusion, L-threonine supplementation had no affect on gut morphology but may have an antioxidant function at 0·2%.
A novel fibre-ensemble level constitutive model for exogenous cross-linked collagenous tissues

Exogenous cross-linking of soft collagenous tissues is a common method for biomaterial development and medical therapies. To enable improved applications through computational methods, physically realistic constitutive models are required. Yet, despite decades of research, development and clinical use, no such model exists. In this study, we develop the first rigorous full structural model (i.e. explicitly incorporating various features of the collagen fibre architecture) for exogenously cross-linked soft tissues. This was made possible, in-part, with the use of native to cross-linked matched experimental datasets and an extension to the collagenous structural constitutive model so that the uncross-linked collagen fibre responses could be mapped to the cross-linked configuration. This allowed us to separate the effects of cross-linking from kinematic changes induced in the cross-linking process, which in turn allowed the non-fibrous tissue matrix component and the interaction effects to be identified. It was determined that the matrix could be modelled as an isotropic material using a modified Yeoh model. The most novel findings of this study were that: (i) the effective collagen fibre modulus was unaffected by cross-linking and (ii) fibre-ensemble interactions played a large role in stress development, often dominating the total tissue response (depending on the stress component and loading path considered). An important utility of the present model is its ability to separate the effects of exogenous cross-linking on the fibres from changes due to the matrix. Applications of this approach include the utilization in the design of novel chemical treatments to produce specific mechanical responses and the study of fatigue damage in bioprosthetic heart valve biomaterials.
Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthritis patients after stimulation with monocytes

It has been reported that nurse-like cells (NLCs) play a critical role in the pathogenesis of rheumatoid arthritis (RA). The interaction between NLCs established from RA patients (RA-NLCs), and freshly isolated blood monocytes was analyzed to further elucidate the pathogenesis of RA. RA-NLC lines were established from the synovium of RA patients. The RA-NLCs were cultured with monocytes freshly isolated from peripheral blood of healthy donors, and induction of interleukin (IL)-6 and IL-8 as well as the mRNA expression of these cytokines was examined. The levels of IL-6 were over 400 times higher in the supernatant from coculture of RA-NLCs and monocytes than in those from cultures of RA-NLCs alone. Anti-tumor necrosis factor (TNF)-α monoclonal antibody inhibited the induction of both cytokine in a dose-dependent fashion, although there was no detectable level of TNF-α in the supernatant from coculture. In addition, coculture of RA-NLCs and monocytes without direct cell contact did not induce cytokine production. To determine IL-6 producing cells, RA-NLCs and monocytes were separated into each fraction after coculture for 24 h. Cocultured RA-NLCs contained approximately 80 times higher IL-6 mRNA than the RA-NLCs cultured alone. The levels of IL-8 were also much higher (about 900 times) in the supernatant from coculture than in those from cultures of RA-NLCs alone. Cocultured RA-NLCs expressed IL-8 mRNA about 620 times higher than those cultured alone. These results indicate that NLCs produce high levels of IL-6 and IL-8 after cell–cell interaction with monocytes/macrophages via membrane-bound TNF-α, and that activation of NLCs by monocytes/macrophages may be involved in the pathogenesis of RA through maintenance of synovial inflammation.
Stabilizing nonpolar/polar side‐chain interactions in the α‐helix

A simplistic, yet often used, view of protein stability is that amino acids attract other amino acids with similar polarity, whereas nonpolar and polar side chains repel. Here we show that nonpolar/polar interactions, namely Val or Ile bonding to Lys or Arg in α‐helices, can in fact be stabilizing. Residues spaced i, i + 4 in α‐helices are on the same face of the helix, with potential to favorably interact and stabilize the structure. We observe that the nonpolar/polar pairs Ile‐Lys, Ile‐Arg, and Val‐Lys occur in protein helices more often than expected when spaced i, i + 4. Partially helical peptides containing pairs of nonpolar/polar residues were synthesized. Controls with i, i + 5 spacing have the residues on opposite faces of the helix and are less helical than the test peptides with the i, i + 4 interactions. Experimental circular dichroism results were analyzed with helix‐coil theory to calculate the free energy for the interactions. All three stabilize the helix with ΔG between −0.14 and −0.32 kcal · mol−1. The interactions are hydrophobic with contacts between Val or Ile and the alkyl groups in Arg or Lys. Side chains such as Lys and Arg can thus interact favorably with both polar and nonpolar residues. Proteins 2001;45:449–455. © 2001 Wiley‐Liss, Inc.
The relationship between insight gained during therapy and long-term outcome in short-term dynamic psychotherapy and cognitive therapy for cluster C personality disorders

Abstract This study examined whether 49 patients from a randomized controlled trial developed insight during therapy and whether insight predicted long-term outcome in short-term dynamic psychotherapy (STDP) and cognitive therapy (CT) for Cluster C personality disorders. Videotaped sessions early and late in treatment were analyzed using the Achievement of Therapeutic Objectives Scale. Patients' level of insight increased significantly during STDP but not CT. After controlling for early symptom change and early insight, insight near the end of therapy predicted improvement of symptom severity and interpersonal functioning during a 2-year follow-up period. These results support the theoretical assumption that insight may be a factor in the change process, central to STDP. Within CT, gain of insight did not predict long-term improvement.
Inter-organizational cooperation in community health organizations.

PURPOSE The purpose of this paper is to examine various aspects related to inter-organizational cooperation and how this phenomenon can be applied to healthcare institutions. DESIGN/METHODOLOGY/APPROACH To fulfil the aim, a qualitative investigation was adopted, focussing on the relationship between public hospital and a higher education institution in Portugal. PRACTICAL IMPLICATIONS The study supports health managers and higher education leaders, and other stakeholders involved inter-organizational cooperation drawing up strategies and understanding inter-organizational cooperation's impact at the regional level. ORIGINALITY/VALUE One contribution is to help fill a gap regarding the empirical research surrounding cooperation between organizations, especially in the health sector, where scientific studies are scarce. It also provides new insights by applying competence-based theory to analyze different approaches to hospital cooperation, which has received scant attention in the health sector.
Solid cancers after bone marrow transplantation.

PURPOSE To evaluate the incidence and associated risk factors of solid cancers after bone marrow transplantation (BMT). PATIENTS AND METHODS We analyzed 2,129 patients who had undergone BMT for hematologic malignancies at the City of Hope National Medical Center between 1976 and 1998. A retrospective cohort and nested case-control study design were used to evaluate the role of pretransplantation therapeutic exposures and transplant conditioning regimens. RESULTS Twenty-nine patients developed solid cancers after BMT, which represents a two-fold increase in risk compared with a comparable normal population. The estimated cumulative probability (+/- SE) for development of a solid cancer was 6.1% +/- 1.6% at 10 years. The risk was significantly elevated for liver cancer (standardized incidence ratio [SIR], 27.7; 95% confidence interval [CI], 1.9 to 57.3), cancer of the oral cavity (SIR, 17.4; 95% CI, 6.3 to 34.1), and cervical cancer (SIR, 13.3; 95% CI, 3.5 to 29.6). Each of the two patients with liver cancer had a history of chronic hepatitis C infection. All six patients with squamous cell carcinoma of the skin had chronic graft-versus-host disease. The risk was significantly higher for survivors who were younger than 34 years of age at time of BMT (SIR, 5.3; 95% CI, 2.7 to 8.6). Cancers of the thyroid gland, liver, and oral cavity occurred primarily among patients who received total-body irradiation. CONCLUSION The risk of radiation-associated solid tumor development after BMT is likely to increase with longer follow-up. This underscores the importance of close monitoring of patients who undergo BMT.
The induction of reparative dentine by enamel proteins.

AIM This study was designed to examine whether enamel matrix derivative (EMD) could induce reparative dentine formation without eliciting adverse side-effects in pulpotomized teeth in the miniature swine. METHODOLOGY Pulpotomy was performed in 36 mandibular incisor teeth from 11 adult miniature swine. Following the surgical procedure, the exposed pulp tissue was treated with EMD or covered with a calcium hydroxide preparation (Dycal). Following an observation period of 3, 4 and 8 weeks, the experimental teeth were extracted and examined using light microscopy and histometric analysis. The total amount of reparative dentine formed in the EMD-treated teeth was calculated as total area using digital histomorphometry analysis of the five central-most sections from each experimental tooth. RESULTS In the EMD-treated teeth, substantial amounts of dentine-like tissue formation consistently led to a complete hard-tissue bridging of the defects. The onset of hard tissue formation could be observed after 2 weeks and was located only on the pulpal wound. More limited dentine formation was also observed in Dycal-treated teeth. However, in these teeth the new hard tissue formed at the expense of pulp chamber width, causing narrowing of root canals. The total amount of reparative dentine formed in the EMD-treated teeth was significantly higher (P<0.005) than in the Dycal-treated specimens. CONCLUSION These results demonstrate the potential of EMD as a biologically active pulp-dressing agent that specifically induces pulpal wound healing and dentine formation in the pulpotomized teeth without affecting the normal function of the remaining pulp.