Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term effects of the proline-rich antimicrobial peptide Oncocin112 on the Escherichia coli translation machinery

Proline-rich antimicrobial peptides (PrAMPs) are cationic antimicrobial peptides unusual for their ability to penetrate bacterial membranes and kill cells without causing membrane permeabilization. Structural studies show that many such PrAMPs bind deep in the peptide exit channel of the ribosome, near the peptidyl transfer center. Biochemical studies of the particular synthetic PrAMP oncocin112 (Onc112) suggest that on reaching the cytoplasm, the peptide occupies its binding site prior to the transition from initiation to the elongation phase of translation, thus blocking further initiation events. We present a superresolution fluorescence microscopy study of the long-term effects of Onc112 on ribosome, elongation factor-Tu (EF-Tu), and DNA spatial distributions and diffusive properties in intact Escherichia coli cells. The new data corroborate earlier mechanistic inferences from studies in vitro. Comparisons with the diffusive behavior induced by the ribosome-binding antibiotics chloramphenicol and kasugamycin show how the specific location of each agent's ribosomal binding site affects the long-term distribution of ribosomal species between 30S and 50S subunits versus 70S polysomes. Analysis of the single-step displacements from ribosome and EF-Tu diffusive trajectories before and after Onc112 treatment suggests that the act of codon testing of noncognate ternary complexes (TCs) at the ribosomal A-site enhances the dissociation rate of such TCs from their L7/L12 tethers. Testing and rejection of noncognate TCs on a sub-ms timescale is essential to enable incorporation of the rare cognate amino acids into the growing peptide chain at a rate of ∼20 aa/s.
Multidisciplinary visual rehabilitation in low- and middle-income countries: a systematic review

Abstract Objective To systematically review the evidence for effectiveness of rehabilitation interventions in people who are visually impaired, living in low- and middle-income countries. Methods Fifteen databases and the grey literature were searched up until February 2020; papers were identified according to eligibility criteria, and assessed for risk of bias. Eligible studies were controlled trials (randomised or non-randomised) of rehabilitation interventions for blind or visually impaired adults or children from low- and middle-income countries. Possible outcomes included visual acuity, activities of daily living, safety, quality of life and psychological status. Results Fifteen eligible studies were identified from India, Turkey, Nigeria, Croatia and Iran. Six studies were randomised, seven were non-randomised trials, and in two the method of allocation was not clear. Participants were adults, children and both adults and children. Seven studies were small (n ≤ 65) and examined the effect of training programmes. Remaining studies compared the effect of low vision aids, economic rehabilitation, goalball, rehabilitation compliance and service delivery methods, including one large four-arm randomised trial (n = 436). Studies measured a variety of outcomes, and mostly showed a positive effect of interventions for pre- and post-intervention assessment, although between intervention group comparisons were often inconclusive. Overall, only four studies had a low risk of bias. Conclusions A lack of high-quality evidence for rehabilitation interventions is a barrier to provision of low vision services in low- and middle-income countries. Future research should focus on establishing effectiveness and cost-effectiveness of devices and models of vision rehabilitation appropriate for low-resource settings. IMPLICATIONS FOR REHABILITATION The systematic review found a lack of high-quality evidence for rehabilitation interventions is a barrier to provision of low vision services in low- and middle-income countries. Consider how visual rehabilitation interventions which have been shown to be effective can be delivered by non-specialists. Ensure that service providers for people who are visually impaired are trained in recognising depression and anxiety and have pathways for referral to mental health services, as appropriate.
Safety evaluation of the canine osteosarcoma vaccine, live Listeria vector

Abstract Canine osteosarcoma (OSA) is an aggressive bone tumour in dogs. Standard‐of‐care treatment typically results in relatively short survival times; thus, alternative treatments are needed to confer a survival advantage. It has been shown that OSA is an immunogenic tumour, suggesting that immune modulation may result in superior outcomes. A cryopreserved, Listeria‐based OSA vaccine was recently developed and an initial study in dogs reported prolonged survival for patients receiving the vaccine in conjunction with standard‐of‐care. The goal of the current observational study was to report on the safety of the lyophilized formulation of this vaccine (the canine OSA vaccine, live Listeria vector [COV‐LLV]) in a group of dogs previously diagnosed with OSA. Forty‐nine (49) dogs received the COV‐LLV and were included for analysis. Adverse events (AEs) noted during and after vaccinations were recorded. The AEs observed were typically mild and self‐limiting, with nausea, lethargy and fever being most common. Four dogs (8%) cultured positive for Listeria (three infections including an amputation site abscess, septic stifle joint and bacterial cystitis; and one dog whose lungs cultured Listeria‐positive on necropsy within 24 hours of COV‐LLV administration). These cases join the previously reported Listeria‐positive thoracic abscess that developed in a canine following use of COV‐LLV. Although uncommon, it is important to realize this clinically significant AE is possible in patients treated with live therapeutic Listeria vaccines. As Listeria is zoonotic, caution is required not only for the patient receiving the vaccine, but also for the health care workers and family caring for the patient.
Effects of Management Regimen, Residual Feed Intake and Reranking on Performance, Carcass and Meat Quality in Beef Steers

EFFECTS OF MANAGEMENT REGIMEN, RESIDUAL FEED INTAKE AND RERANKING ON PERFORMANCE, CARCASS AND MEAT QUALITY IN BEEF STEERS Natalie N. Ferriman Advisor: University of Guelph, 2018 Dr. Ira B. Mandell Residual feed intake (RFI) is a measurement of feed efficiency and is becoming a popular trait used in genetic selection. This study evaluated the effects of RFI classification on beef cattle performance, carcass and meat quality and its repeatability between growing and finishing phases of production. Cattle were managed on two different nutritional management regimens consisting of finishing on a high grain diet or backgrounding cattle prior to being finished on a high grain diet. Extensive RFI reranking occurred between production phases. Reranking was positively correlated with longissimus muscle area but did not influence other carcass and meat quality parameters. Growing phase RFI classification had a minimal effect on carcass traits, while low RFI classified steers in the finishing phase produced bigger ribeyes. High RFI steers produced juicier and more tender beef compared to low RFI steers assessed using taste panel and consumer evaluations.
Biology of Oestrogen-Receptor Positive Primary Breast Cancer in Older Women with Utilisation of Core Needle Biopsy Samples and Correlation with Clinical Outcome

The majority of biological profiling studies use surgical excision (SE) samples, excluding patients receiving nonsurgical and neoadjuvant therapy. We propose using core needle biopsy (CNB) for biological profiling in older women. Over 37 years (1973–2010), 1 758 older (≥70 years) women with operable primary breast cancer attended a dedicated clinic. Of these, 693 had sufficient quality CNB to construct tissue microarray (TMA). The pattern of biomarkers was analysed in oestrogen receptor (ER)-positive cases, using immunohistochemistry and partitional clustering analysis. The biomarkers measured were: progesterone receptor (PgR), Ki67, Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor (HER)-2, HER3, HER4, p53, cytokeratins CK5/6 and CK7/8, Mucin (MUC)1, liver kinase B1 (LKB1), Breast Cancer Associated gene (BRCA) 1, B-Cell Lymphoma (BCL)-2, phosphate and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Amplified in breast cancer 1 (AIB1). CNB TMA construction was possible in 536 ER-positive cases. Multivariate analysis showed progesterone receptor (PgR) (p = 0.015), Ki67 (p = 0.001), and mucin (MUC)1 (p = 0.033) as independent predictors for breast-cancer-specific survival (BCSS). Cluster analysis revealed three biological clusters, which were consistent with luminal A, luminal B, and low-ER luminal. The low-ER luminal cluster had lower BCSS compared to luminal A and B. The presence of the low-ER luminal cluster unique to older women, identified in a previous study in SE TMAs in the same cohort, is confirmed. This present study is novel in its use of core needle biopsy tissue microarrays to profile the biology of breast cancer in older women.
COVID-19 lethality in non-elderly individuals in cities with different Human Development Index

Dear Editor, Many risk factors are associated with COVID-19 mortality, especially in those aged >65 years and associated with co-morbidities. At first, it was assumed that people aged <65 years have a lower risk of dying from COVID-19. However, SARV-CoV-2 is currently spreading quickly in poor regions and differences in COVID-19 have been shown, especially by age group. In Brazil, around 15% of COVID-19 deaths have been in people aged <50 years. In Mexico, around 25% of fatalities have been aged 25–49 years. In India, nearly half of those who died were aged <60 years. These rates are 10 times greater than in Italy or Spain. Brazil has many regional inequalities. About 13.5 million Brazilians live in extreme poverty, according to the World Bank definition (daily income $1.25). Pernambuco state, in the Northeast of Brazil, is the poorest region in the country. Pernambuco has 9278 million inhabitants in 185 cities that have shown different COVID19 mortality rates: 4.2–39.7 per 100,000 inhabitants. The Human Development Index (HDI) is an instrument used to evaluate the level of social welfare and economic development of a population. The HDI is the statistical index, between 0 and 1, of three indicators: life expectancy; years of schooling; and income per capita. The HDI reflects the social and economic status of people in different regions. Recife, the capital and largest city of Pernambuco state, has the highest HDI (0.772) and Manari has the lowest HDI (0.487). Briefly, we analyzed the distribution of COVID-19 lethality in non-elderly people (aged <60 years). COVID-19 lethality data were taken from 12 cities of Pernambuco state, Brazil. The data are presented in Table 1. It was observed that COVID-19 lethality in people aged <60 years was inversely correlated with the HDI (Pearson’s correlation coefficient 1⁄4 –0.7351). People with a disadvantaged socioeconomic status had a higher COVID-19 lethality, including younger people. Very high population density and low levels of income and education affect living conditions in many ways, such as lack of food, precarious hygiene standards, and overcrowded and deprived housing conditions, all of which puts these people at greater risk of being exposed to SARS-CoV-2. In addition, nutritional deficiencies are common in these people, which competes for immunological deficiencies. Besides, disadvantaged people frequently have delayed medical care, which may worsen the prognosis of COVID-19. People with a disadvantaged socioeconomic status may be considered high-risk populations at the time of the COVID-19 pandemic.
Recombinant human MMP-2 associated with monoolein improves bone repair.

OBJECTIVE The main objective of the present study was to investigate the possible osteostimulatory action of recombinant human matrix metalloproteinase-2 (rhMMP-2) implanted in a bone defect made in calvaria of rats, bounded to the monoolein as carrier. METHODS Forty-four adult male Wistar rats (about 600 g body weight) underwent surgery in order to create a spherical defect in parietal bone on the right side of the median sagittal suture by using 4 mm diameter of a trephine drill. Animals were divided into three groups: no treatment (control, C), treatment with rhMMP-2 diluted in monoolein liquid crystal (rhMMP-2) and negative control with monoolein (M). The groups were divided into two experimental times, 2- and 4-weeks of experimental time. RESULTS The rate of new-formed bone, estimated by the number of points on new-formed cancellous bone, was in enhanced rhMMP-2 group in both periods in comparison to C or M groups. CONCLUSION There was no difference in bone neoformation between second to fourth week within groups. In the present study, monoolein alone had a negative role in the post-operative surgery, but monoolein associated with +rhMMP-2 had a positive role on releasing rhMMP-2 and enhance the rate of new-formed bone (Tab. 1, Fig. 5, Ref. 71).
Synthesis of Peptides with α,β-Dehydroamino Acids, V. Coupling experiments with C-Terminal Dehydrophenylalanine and Dehydroalanine Residues

N-Protected model dipeptides of C-terminal (Z)-ΔPhe and ΔAla couple with glycine esters after activation with either diphenyl phosphorazidate (DPPA), N-cyclohexyl-N′-[2-(N-methylmorpholinio)ethyl]carbodiimide p-toluenesulfonate (WSC), N,N′-dicyclohexylcarbodiimide + 1-hydroxybenzotriazole (DCC + HOBt), or the mixed anhydride (MA) with isobutyl chlorocarbonate to give in good or mostly moderate yields the (Z)-ΔPhe-containing tripeptides 1 – 9 and ΔAla-containing tripeptides 11 – 19, respectively. In the MA and DPPA methods, further acylation products 20a – d are formed to a great extent, expecially during the ΔAla peptide syntheses. (E)-TFA-Gly-ΔPhe and Gly-OtBu, irrespective of the activation method, afford mixtures of (Z)- and (E)-tripeptides 1 and 10 with small amounts of the (E)-isomer 10. Addition products to the ΔAla double bond were isolated. They are azidotripeptides 21a – 1 formed if the DPPA method is used. An adduct 22 from tripeptide and HOBt arises from the WSC + HOBt method. In the MA method, loss of the ΔAla residue is observed and X-Gly-Gly-OY 23a and b are obtained. The previously N-deprotected tripeptides 1 and 11 were condensed with Boc-Gly-OSu to yield the tetrapeptides 24 and 25. Synthese von Peptiden mit α,β-Dehydroaminosauren, V. – Kupplungsexperimente mit C-terminalen Dehydrophenylalanin- und Dehydroalaninresten N-Geschutzte Modelldipeptide mit C-terminalen (Z)-ΔPhe und ΔAla reagieren mit Glycinestern nach Aktivierung entweder mit Diphenylphosphorazidat (DPPA), N-Cyclohexyl-N′-[2-(N-methylmorpholinio)ethyl] carbodiimid-(p-toluolsulfonat) (WSC), N,N′-Dicyclohexyl-carbodiimid + 1-Hydroxybenzotriazol (DCC + HObt) oder dem gemischten Anhydrid (MA) mit Isobutylchlorcarbonat in guten bis masigen Ausbeuten zu (Z-)ΔPhe- (1 – 9) und ΔAla-enthaltenden (11 – 19) Tripeptiden. Bei der MA- und DPPA-Methode werden zusatzlich die Acylierungsprodukte 20a – d erhalten, vor allem bei der Synthese von ΔAla-Peptiden. Die Reaktion von (E)-TFA-Gly-ΔPhe mit Gly-OtBu liefert, unabhangig von der Aktivierungsmethode, Mischungen der (Z)- und (E)- Tripeptide 1 und 10, wobei nur wenig des (E)-Isomeren 10 isoliert wird. Als Additionsprodukte an die ΔAla-Doppelbindung werden die Azidtripeptide 21a – i bei der DPPA-Methode und ein Addukt 22 aus Tripeptid und HOBt bei der (WSC + HOBt)-Methode erhalten. Bei der MA-Methode beobachtet man Verlust des ΔAla-Restes, und X-Gly-Gly-OY 23a und b werden erhalten. Die Tripeptide 1 und 11 werden nach vorangehender Entfernung der N-Schutzgruppe mit Boc-Gly-OSu zu den Tetrapeptiden 24 und 25 kondensiert.
Where Do Adolescents Eat Less-Healthy Foods? Correspondence Analysis and Logistic Regression Results from the UK National Diet and Nutrition Survey

This study investigates the relationship between the consumption of foods and eating locations (home, school/work and others) in British adolescents, using data from the UK National Diet and Nutrition Survey Rolling Program (2008–2012 and 2013–2016). A cross-sectional analysis of 62,523 food diary entries from this nationally representative sample was carried out for foods contributing up to 80% total energy to the daily adolescent’s diet. Correspondence analysis (CA) was used to generate food–location relationship hypotheses followed by logistic regression (LR) to quantify the evidence in terms of odds ratios and formally test those hypotheses. The less-healthy foods that emerged from CA were chips, soft drinks, chocolate and meat pies. Adjusted odds ratios (99% CI) for consuming specific foods at a location “other” than home (H) or school/work (S) in the 2008–2012 survey sample were: for soft drinks, 2.8 (2.1 to 3.8) vs. H and 2.0 (1.4 to 2.8) vs. S; for chips, 2.8 (2.2 to 3.7) vs. H and 3.4 (2.1 to 5.5) vs. S; for chocolates, 2.6 (1.9 to 3.5) vs. H and 1.9 (1.2 to 2.9) vs. S; and for meat pies, 2.7 (1.5 to 5.1) vs. H and 1.3 (0.5 to 3.1) vs. S. These trends were confirmed in the 2013–2016 survey sample. Interactions between location and BMI were not significant in either sample. In conclusion, public health policies to discourage less-healthy food choices in locations away from home and school/work are warranted for adolescents, irrespective of their BMI.
Cortical atrophy mediates the accumulating effects of vascular risk factors on cognitive decline in the Alzheimer’s disease spectrum

There are increasing concerns regarding the association of vascular risk factors (VRFs) and cognitive decline in the Alzheimer's disease (AD) spectrum. Currently, we investigated whether the accumulating effects of VRFs influenced gray matter volumes and subsequently led to cognitive decline in the AD spectrum. Mediation analysis was used to explore the association among VRFs, cortical atrophy, and cognition in the AD spectrum. 123 AD spectrum were recruited and VRF scores were constructed. Multivariate linear regression analysis revealed that higher VRF scores were correlated with lower Mini-Mental State Examination scores and higher Alzheimer's Disease Assessment Scale-Cognitive Subscale scores, indicating higher VRF scores lead to severer cognitive decline in the AD spectrum. In addition, subjects with higher VRF scores suffered severe cortical atrophy, especially in medial prefrontal cortex and medial temporal lobe. More importantly, common circuits of VRFs- and cognitive decline associated with gray matter atrophy were identified. Further, using mediation analysis, we demonstrated that cortical atrophy regions significantly mediated the relationship between VRF scores and cognitive decline in the AD spectrum. These findings highlight the importance of accumulating risk in the vascular contribution to AD spectrum, and targeting VRFs may provide new strategies for the therapeutic and prevention of AD.
“I Have Guys Call Me and Say ‘I Can’t Be the Victim of Domestic Abuse’”: Exploring the Experiences of Telephone Support Providers for Male Victims of Domestic Violence and Abuse

While previous studies have begun to provide evidence on the experiences of male victims of domestic violence and abuse (DVA), current understanding in this area is still limited, and subject to narrow methods of inquiry. Moreover, little is known regarding the challenges of providing support to men in abusive relationships, and how barriers to effective service engagement are experienced by both men and service practitioners. This is an important area for exploration, as the gender-specific experiences and needs of men have been historically overlooked within academic research and service provision. The present study therefore had two principal aims: first, to provide more detailed information regarding the nature and context of abuse toward, and help-seeking experiences of, male victims, and second, to explore the experiences of those supporting abused men. Semi-structured interviews were conducted with four call handlers at a U.K. domestic abuse charity supporting male victims. Transcribed interviews were subjected to thematic analysis, revealing a superordinate theme of stereotypes and expectations of men which affected all the other three overarching and eight subthemes, including those detailing the range and severity of abuse suffered, the role of family and friends, barriers to reporting for abused men, and challenges in supporting them. Implications for services working with male victims of DVA are discussed: centered around the need for recognition, increased awareness, increased resourcing, and the provision of gender-inclusive services catering for the gender-specific needs of men.
Dynamics of carving runs in alpine skiing. II.Centrifugal pendulum with a retractable leg

ABSTRACT In this paper, we present an advanced model of centrifugal pendulum where its length is allowed to vary during swinging. This modification accounts for flexion and extension of skier’s legs when turning. We focus entirely on the case where the pendulum leg shortens near the vertical position, which corresponds to the most popular technique for the transition between carving turns in ski racing, and study the effect of this action on the kinematics and dynamics of these turns. In particular, we find that leg flexion on approach to the summit point is a very efficient way of preserving the contact between skis and snow. The up and down motion of the skier centre of mass can also have a strong effect of the peak ground reaction force experienced by skiers, particularly at high inclination angles. Minimisation of this motion allows a noticeable reduction of this force and hence of the risk of injury. We make a detailed comparison between the model and the results of a field study of slalom turns and find a very good agreement. This suggests that the pendulum model is a useful mathematical tool for analysing the dynamics of skiing.
The effects of moderate alterations in adrenergic activity on acute appetite regulation in obese women: A randomised crossover trial

Background: Previous evidence has demonstrated that serum leptin is correlated with appetite in combination with, but not without, modest exercise. Aim: The present experiments investigated the effects of exogenous adrenaline and α/β adrenoceptor blockade in combination with moderate exercise on serum leptin concentrations, appetite/satiety sensations and subsequent food intake in obese women. Methods: A total of 10 obese women ((mean ± SEM), age: 50 (1.9) years, body mass index 36 (4.1) kg/m2, waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/β adrenergic blocker (labetalol, 100 mg orally) versus moderate exercise plus placebo; experiment 2: adrenaline infusion for 20 minutes versus saline infusion. Appetite/satiety and biochemistry were measured at baseline, pre- and immediately post-intervention, then 1 hour post-intervention (i.e., before dinner). Food intake was assessed via ad libitum buffet-style dinner. Results: No differences were found in appetite/satiety, subsequent food intake or serum leptin in any of the studies (experiment 1 or experiment 2). In experiment 1, blood glucose was higher (p < 0.01) and plasma free fatty acids lower (p = 0.04) versus placebo. In experiment 2, plasma free fatty acids (p < 0.05) increased after adrenaline versus saline infusion. Conclusions: Neither inhibition of exercise-induced adrenergic activity by combined α/β adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.