Miracle-dz/UniFAR-FTUs huggingface dataset:
FHOD1 is a combined actin filament capping and bundling factor that selectively associates with actin arcs and stress fibers

Summary Formins are actin polymerization factors that are known to nucleate and elongate actin filaments at the barbed end. In the present study we show that human FHOD1 lacks actin nucleation and elongation capacity, but acts as an actin bundling factor with capping activity toward the filament barbed end. Constitutively active FHOD1 associates with actin filaments in filopodia and lamellipodia at the leading edge, where it moves with the actin retrograde flow. At the base of lamellipodia, FHOD1 is enriched in nascent, bundled actin arcs as well as in more mature stress fibers. This function requires actin-binding domains located N-terminally to the canonical FH1–FH2 element. The bundling phenotype is maintained in the presence of tropomyosin, confirmed by electron microscopy showing assembly of 5 to 10 actin filaments into parallel, closely spaced filament bundles. Taken together, our data suggest a model in which FHOD1 stabilizes actin filaments by protecting barbed ends from depolymerization with its dimeric FH2 domain, whereas the region N-terminal to the FH1 domain mediates F-actin bundling by simultaneously binding to the sides of adjacent F-actin filaments.
Domain analysis of Kv6.3, an electrically silent channel

The subunit Kv6.3 encodes a voltage‐gated potassium channel belonging to the group of electrically silent Kv subunits, i.e. subunits that do not form functional homotetrameric channels. The lack of current, caused by retention in the endoplasmic reticulum (ER), was overcome by coexpression with Kv2.1. To investigate whether a specific section of Kv6.3 was responsible for ER retention, we constructed chimeric subunits between Kv6.3 and Kv2.1, and analysed their subcellular localization and functionality. The results demonstrate that the ER retention of Kv6.3 is not caused by the N‐terminal A and B box (NAB) domain nor the intracellular N‐ or C‐termini, but rather by the S1–S6 core protein. Introduction of individual transmembrane segments of Kv6.3 in Kv2.1 was tolerated, with the exception of S6. Indeed, introduction of the S6 domain of Kv6.3 in Kv2.1 was enough to cause ER retention, which was due to the C‐terminal section of S6. The S4 segment of Kv6.3 could act as a voltage sensor in the Kv2.1 context, albeit with a major hyperpolarizing shift in the voltage dependence of activation and inactivation, apparently caused by the presence of a tyrosine in Kv6.3 instead of a conserved arginine. This study suggests that the silent behaviour of Kv6.3 is largely caused by the C‐terminal part of its sixth transmembrane domain that causes ER retention of the subunit.
Does plot size matter? Evidence from maize production in Babati District, Tanzania

ABSTRACT Debates about optimal farm structure and size have a long history in agricultural economics. Agricultural and development economists argue for an inverse relationship between farm size and productivity, but debates around this remain inconclusive. This article provides a case from maize production in Babati District, Tanzania. The efficiency level of 122 sampled smallholder farmers was estimated and found to be 62.3%, suggesting 37.7% of inefficiencies. A U-shape relationship between plot size and efficiency scores was found. There was high efficiency at plots <2 ha, compared to 2 ha and 3 ha, followed by efficiency at plots >4 ha. Policies stimulating small- and large-scale farms in the country are imperative.
The Impact of Bank Credit on Employment Formality: Evidence from Uruguay

ABSTRACT This article examines the effect of bank credit on employment formalization in Uruguay. Using a difference-in-differences methodology the article finds that financial deepening decreases informality, especially in more financially dependent sectors. In addition, the effect is found to be greater among women and older workers. In the period under analysis the economy underwent a severe economic crisis and bank credit contracted sharply, but we find no evidence that the effect of bank credit on employment formality changed over time.
Primary Aldosteronism or Not Primary Aldosteronism: Is This Now the Question in Normotension?

See related article, pp 950–956 Primary aldosteronism (PA) within hypertensive populations is no longer regarded as being a rare phenomenon. Although some debate around its overall frequency remains, one of the most robust studies in recent years describes a prevalence of ≈10% in unselected hypertensives1; this may rise to ≤20% in subjects with resistant hypertension.2 In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure introduced a new hypertension category defined as prehypertension to describe individuals with systolic blood pressure ranging from 120 to 139 mm Hg and diastolic blood pressure from 80 to 89 mm Hg.3 Thus, in parallel with this change in perception of blood pressure classification and recognition that hypertension is not an arbitrary definition, so have there been attempts to demonstrate disordered aldosterone regulation within normotensive or prehypertensive cohorts. The concept of altered aldosterone dynamics predisposing to hypertension over time was first demonstrated in the Framingham Offspring study in which serum aldosterone was measured in a cohort of 1688 normotensive participants.4 During a 4-year follow-up period, when compared with the lowest quartile of serum aldosterone, the highest quartile was associated with an 1.6-fold increased risk of elevated blood pressure (95% confidence interval, 1.19–2.14) and a similar risk of overt hypertension (95% confidence interval, 1.05–2.46). Therefore, although there is evidence that increased aldosterone levels (still within the physiological range) can predispose …
Essential Role of the Adhesion Receptor LFA-1 for T Cell-Dependent Fulminant Hepatitis1

Viral hepatitis affects more than 2 billion people worldwide. In particular, no effective treatment exists to abrogate death and liver damage in fulminant hepatitis. Activation of T cells is an initial and critical event in the pathogenesis of liver damage in autoimmune and viral hepatitis. The precise molecular mechanisms that induce T cell-mediated hepatocyte injury remain largely unclear. In mice, T cell-dependent hepatitis and acute liver damage can be modeled using ConA. In this study, we examined the role of the adhesion receptor LFA-1 in ConA-induced acute hepatic damage using LFA-1−/− (CD11a) mice. Massive liver cell apoptosis and metabolic liver damage were observed in LFA-1+/+ mice following ConA injection. By contrast, LFA-1−/− mice were completely resistant to ConA-induced hepatitis and none of the LFA-1−/− mice showed any hepatic damage. Whereas activated hepatic T cells remained in the liver in LFA-1+/+ mice, activated T cells were rapidly cleared from the livers of LFA-1−/− mice. Mechanistically, T cells from LFA-1−/− mice showed markedly reduced cytotoxicity toward liver cells as a result of impaired, activation-dependent adhesion. Importantly, adoptive transfer of hepatic T cells from LFA-1+/+ mice, but not from LFA-1−/− mice, sensitized LFA-1−/− mice to ConA-induced hepatitis. Thus, LFA-1 expression on T cells is necessary and sufficient for T cell-mediated liver damage in vivo. These results provide the first genetic evidence on an adhesion receptor, LFA-1, that has a crucial role in fulminant hepatitis. These genetic data identify LFA-1 as a potential key target for the treatment of T cell-mediated hepatitis and the prevention of liver damage.
Intrinsic and extrinsic factors influencing eggshell penetration by Salmonella :

To prevent penetration of Salmonella into eggs, a clear understanding of various factors influencing bacterial penetration could be a valuable tool in planning intervention strategies. Penetration was assessed by replacing the egg contents with a selective medium that allowed visualising Salmonella growth on the inside of the shell by candling. Only eggshells without visual abnormalities were used. Eggs from one ISA-Brown Warren laying flock were used to determine the effect of hen age and storage conditions. A faster appearance of penetration spots was observed with increasing storage temperatures possibly caused by increased growth rates of SE on the agar. Although shell characteristics differed with hen age, hen age did not influence SE penetration. Eggshell penetration varied greatly between eggs bought at a warehouse. Only 6% of the eggs from “free range” hens and 16% of the “white” eggs were contaminated. The remaining eggs (bio, columbus and brown) were contaminated at a frequency of ca 33%. Eggs from both ISA-Brown Warren and Bovan Goldline hens kept in 2 types of housing system (furnished cage versus aviary) and fed 2 types of feed (standard feed versus feed containing corn cob mix) were tested. The breed of the hen neither the housing system did affect the eggshell penetration by SE. Eggs from hens fed CCM were more frequently penetrated. Hence, the feed can play an important role to reduce eggshell penetration. No correlations were observed between any of the shell characteristics studied and the ability of SE to penetrate the shell, although the egg(shell) characteristics of the various eggs differed greatly. One factor that is of major significance is the growth of SE on the shell because shell contamination at the end of storage and SE penetration were highly correlated. Thus, SE growth on the shell should be prevented.
Cost of Capital of Government's Claim and the Present Value of Tax Shields

In this paper we derive a general formula for the cost of capital of government's claim (rg). Given our valuation framework that distinguishes three claimholders-equity holders, debt holders and government-we show for the models used in Myers (1974), Miles and Ezzell (1980) and Harris and Pringle (1985), that the present value of tax shields is equal to the difference between the present value of the expected taxes paid by the unlevered firm and the levered firm, with each of the models' implied rg as discount rate. We provide a numerical example of how to calculate rg and we give a logic explanation for the low implied rgs of Miles and Ezzell's and Harris and Pringle's model.
Predicting functional decline in older patients undergoing cardiac surgery.

BACKGROUND a growing number of older patients undergo cardiac surgery. Some of these patients are at increased risk of post-operative functional decline, potentially leading to reduced quality of life and autonomy, and other negative health outcomes. First step in prevention is to identify patients at risk of functional decline. There are no current published tools available to predict functional decline following cardiac surgery. OBJECTIVE to validate the identification of seniors at risk-hospitalised patients (ISAR-HP), in older patients undergoing cardiac surgery. DESIGN AND METHODS a multicenter cohort study in cardiac surgery wards of two university hospitals with follow-up 3 months after hospital admission. INCLUSION CRITERIA consecutive cardiac surgery patients, aged ≥65. Functional decline was defined as a decline of at least one point on the Katz ADL Index at follow-up compared with preadmission status. RESULTS 475 patients were included, 16% of all patients and 20% of patients ≥70+ suffered functional decline. The amended prediction model predicted functional decline using four criteria: preadmission need for daily assistance in instrumental activities of daily living, use of a walking device, need for assistance in travelling and no education after age 14. Area under the receiver operating curve for patients ≥70 it was 0.73. For the amended ISAR-HP sensitivity, specificity, positive and negative predictive values were 85, 48, 29 and 93%, respectively. CONCLUSIONS the amended ISAR-HP used in older cardiac surgery patients showed good discriminative values at score ≥1, supporting the generalisability of this prediction model for this patient group.
THE APPLICATION OF THE MINIMUM FOOD SECURITY QUOTA IN RESPONSE TO A POTENTIAL NATURAL DISASTER: THE CASE OF MALAYSIA

Following the Minimum Food Security Quota (MFS-Quota) proposed by Ruiz Estrada (2010) to evaluate and determine the food sustainability of any given country in the event of any natural disaster, this paper sets out to apply the MFS-Quota to test Malaysia’s food storage and supply readiness for any potential natural disaster that may critically affect the socio-economic and political well-being of the country. The primary objective of the MFS-Quota is to calculate the approximate amount of annual food storage that any country needs in order to subsist through any potential natural disaster. As such, any country could build its own MFS-Quota based on its agriculture production system(s) and national food policy focus.
Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes

We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.33–0.94; p=0.028), and a positive association was found for having ≥1 mutation in a DNA methylation-related gene: TET2, DNMT3A, IDH1 and/or IDH2 (OR: 4.76, 95%CI: 1.31–17.27; p=0.017). Mutations in TP53 (hazard ratio [HR]: 3.88; 95%CI: 1.94–7.75) and EZH2 (HR: 2.50; 95%CI: 1.23–5.09) were associated with shorter overall survival. Meta-analysis of 6 studies plus present data (n=815 patients) allowed assessment of the association of drug response with mutations in 9 candidate genes: ASXL1, CBL, EZH2, SF3B1, SRSF2, TET2, DNMT3A, IDH1/2 and TP53. TET2 mutations predicted a more favorable drug response compared with ‘wild-type’ peers (pooled OR: 1.67, 95%CI: 1.14–2.44; p=0.01). In conclusion, mutations in the DNA methylation pathway, especially TET2 mutations, and low number of total mutations are associated with a better response to azacitidine.
On the low-discrepancy sequences and their use in MOEA/D for high-dimensional objective spaces

In spite of the success of the multi-objective evolutionary algorithm based on decomposition (MOEA/D), the generation of weights for problems having many objectives, continues to be an open research problem. In this paper, we introduce a new methodology based on low-discrepancy sequences to generate the weights vectors employed by MOEA/D. We analyze and compare the proposed methodology using different low-discrepancy sequences and its impact in the search process of MOEA/D. The proposed approach is evaluated in problems having many objective functions (up to 15 objectives). We show the flexibility and ease of use of this type of sequences when adopting them to generate the weights of MOEA/D.
Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations.

OBJECTIVE The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations. DESIGN One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study. METHODS Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization. RESULTS The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; P=0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; P=0.011, OR=2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD. CONCLUSIONS The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.
Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases

The innovation of reprogramming somatic cells to induced pluripotent stem cells provides a possible new approach to treat β-thalassemia and other genetic diseases such as sickle cell anemia. Induced pluripotent stem (iPS) cells can be made from these patients' somatic cells and the mutation in the β-globin gene corrected by gene targeting, and the cells differentiated into hematopoietic cells to be returned to the patient. In this study, we reprogrammed the skin fibroblasts of a patient with homozygous β0 thalassemia into iPS cells, and showed that the iPS cells could be differentiated into hematopoietic cells that synthesized hemoglobin. Prenatal diagnosis and selective abortion have been effective in decreasing the number of β-thalassemia births in some countries that have instituted carrier screening and genetic counseling. To make use of the cells from the amniotic fluid or chorionic villus sampling that are used for prenatal diagnosis, we also showed that these cells could be reprogrammed into iPS cells. This raises the possibility of providing a new option following prenatal diagnosis of a fetus affected by a severe illness. Currently, the parents would choose either to terminate the pregnancy or continue it and take care of the sick child after birth. The cells for prenatal diagnosis can be converted into iPS cells for treatment in the perinatal periods. Early treatment has the advantage of requiring much fewer cells than adult treatment, and can also prevent organ damage in those diseases in which damage can begin in utero or at an early age.
Demographic and Clinical Characteristics of 4556 Type 2 Diabetes Mellitus Patients at a Tertiary Care Hospital in Southern Punjab

Objective The objective of this study was to analyze the demographic profile of type 2 diabetes mellitus (DM) patients presenting to a tertiary care hospital of Southern Punjab, Pakistan. Methods This descriptive study was carried out at the Diabetic Outdoor Nishtar Hospital Multan from 2013 to 2018 after taking approval from the Institutional Ethical Review Committee. All patients were evaluated in detail after obtaining informed consent. Results Data of 4,556 patients with type 2 DM were analyzed. There were 2549 (55.9%) female and 2007 (44.1%) male participants in our study. The mean age of our study population was 47.72 years with a standard deviation (SD) of 10.82 years. Seventy-nine percent of the patients belonged to urban areas. Symptoms of polyuria, polydipsia, and polyphagia were found in 72%, 67%, and 59% of patients, respectively. Hypertension was found in 3391 (74%) patients. The mean waist circumference (WC) was 102.85 cm with an SD of 18.14 cm. The mean waist to hip ratio (WHR) was 1.02 with an SD of 0.102. The mean body mass index (BMI) was 26.50 with an SD of 5.57 kg/m2. Obesity (BMI >27 kg/m2) was found in 1,891 (41.5%) of patients. Central obesity was found in 80.7% and 94.7% of type 2 DM patients according to the WC and WHR cutoff, respectively. Females were more likely to be obese than males in all parameters of obesity. Central obesity was much more common in female diabetics as compared to male diabetics (odds ratio 4 in WHR criteria versus odds ratio 1.8 in BMI criteria for obese). Conclusion Diabetes is more prevalent in females than males and especially affects the middle age group. Hypertension and obesity are important comorbid associations of DM. WC and WHR are more reliable indicators of obesity in type 2 DM patients especially in this part of the world. Central obesity was more prevalent in female type 2 DM patients.
Outbreak of Nosocomial Infections Due to Extended-Spectrum β-Lactamase-Producing Strains of Enteric Group 137, a New Member of the Family Enterobacteriaceae Closely Related toCitrobacter farmeri and Citrobacter amalonaticus

ABSTRACT A member of the Enterobacteriaceae initially identified as Kluyvera cryocrescens by the MicroScan Gram-Negative Combo 13 panel caused an outbreak of nosocomial infections in four patients (pneumonia, n = 2; urinary tract infection,n = 1; wound infection, n = 1) and urinary tract colonization in one patient. When the strains were tested by the Enteric Reference Laboratory of the Centers for Disease Control and Prevention, biochemical results were most compatible withYersinia intermedia, Kluyvera cryocrescens, andCitrobacter farmeri but identification scores were low and test results were discrepant. However, when the biochemical test profile was placed in the computer database as a new organism, all strains were identified as the organism with high identification scores (0.999968 to 0.999997) and no discrepant test results. By 16S rRNA sequence analysis the organism clustered most closely with, but was distinct from, Citrobacter farmeri and Citrobacter amalonaticus. Based on its unique biochemical profile and rRNA sequence, this organism is designated Enteric Group 137. Restriction endonuclease analysis and taxonomic antibiograms of strains causing the outbreak demonstrated a single clone of Enteric Group 137, and antibiotic susceptibility testing revealed the presence of extended-spectrum β-lactamase (ESBL) resistance. Enteric Group 137 appears to be a new opportunistic pathogen that can serve as a source of ESBL resistance in the hospital.
Making Slums Into Attractions: The Role of Tour Guiding in the Slum Tourism Development in Kibera and Dharavi

This article investigates how slums are made into a tourism attraction. We focus in particular on the role of tour guides and tour guiding operations in this process. In the tourism literature in general tour guiding has been subject to much reflection and debate. However, tour guides' role in enabling tourism in new places, in the making of attractions, has not been discussed much. Also, in the emerging research on slum tourism little attention has been given to tour guides and their roles. This article addresses both research gaps in providing insights into tour guiding in slum tourism, and by addressing the roles of tour guides in attraction making through a comparative analysis of tourism in two slums: Dharavi, in Mumbai, India, and Kibera, in Nairobi, Kenya. Based on empirical research of tour guiding operations we found that different levels of formality in tour guiding coexist across destinations. Formal tour guiding operations are more successful in establishing a slum as an attraction as they enable significant growth in tourist numbers. However, formal tour guiding operations and strong international participation in their foundation are factors that seem to undermine to some extent the creation of intimate and authentic encounters in tour guiding, preferred by some tourists. This leaves space for more informal tour guiding, with strong local ties, which are better placed to produce intimate experiences.