Miracle-dz/UniFAR-FTUs huggingface dataset:
Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies.

BACKGROUND Mature podocytes are growth-arrested because of the expression of cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a dysregulation of their differentiated phenotype and proliferate. METHODS To shed light on the mechanism underlying podocyte proliferation in CG, we analyzed the expression of the proliferation marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and podocyte differentiation marker synaptopodin in eight cases of HIVAN and two cases of idiopathic CG. Normal fetal and adult kidneys served as controls. RESULTS Both HIVAN and idiopathic CG showed a marked reduction in the expression of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli, respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli. Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli. CONCLUSIONS The loss of p27 and p57 leading to expression of cyclin A may account for the activation of podocyte proliferation in CG. Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell cycle in CG. These novel findings offer insight into the molecular regulation of mature podocyte differentiation. Podocyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.
Organs-on-a-chip: a new tool for drug discovery

Introduction: The development of emerging in vitro tissue culture platforms can be useful for predicting human response to new compounds, which has been traditionally challenging in the field of drug discovery. Recently, several in vitro tissue-like microsystems, also known as ‘organs-on-a-chip’, have emerged to provide new tools for better evaluating the effects of various chemicals on human tissue. Areas covered: The aim of this article is to provide an overview of the organs-on-a-chip systems that have been recently developed. First, the authors introduce single-organ platforms, focusing on the most studied organs such as liver, heart, blood vessels and lung. Later, the authors briefly describe tumor-on-a-chip platforms and highlight their application for testing anti-cancer drugs. Finally, the article reports a few examples of other organs integrated in microfluidic chips along with preliminary multiple-organs-on-a-chip examples. The article also highlights key fabrication points as well as the main application areas of these devices. Expert opinion: This field is still at an early stage and major challenges need to be addressed prior to the embracement of these technologies by the pharmaceutical industry. To produce predictive drug screening platforms, several organs have to be integrated into a single microfluidic system representative of a humanoid. The routine production of metabolic biomarkers of the organ constructs, as well as their physical environment, have to be monitored prior to and during the delivery of compounds of interest to be able to translate the findings into useful discoveries.
CodePlus — Designing an after school computing programme for girls

Women are underrepresented in the field of Computer Science. This project aims to help Secondary School girls develop an insight into the role computers play in society and to learn some of the key skills in computing including computer programming. Exposure to Computer Science, in home or school environments, and encouragement from family and peers are leading factors that influence girls' decisions to pursue careers in Computer Science. Other factors include the girls' perception of their own problem solving ability, an understanding of the diverse applications of Computer Science and related career paths and the potential for positive social impact. This paper describes the design of an after school computing programme, CodePlus, which uses a novel 21st Century learning model. Pre and post questionnaire are being used to explore girls intentions to study CS, their confidence to study CS, perception of CS as a career, gender perception of CS and IT profession and self-efficacy following participation in the CodePlus programme. Preliminary results comparing pre questionnaire results with a male control group highlight differences in how girls see themselves in terms of CS capabilities and their future potential. Initial post questionnaire findings show a significant increase in the participants' perceived programming ability.
Cardiac hypertrophy and remodeling in relation to ACE and angiotensinogen genes genotypes in Chinese dialysis patients.

BACKGROUND Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis patients remains unknown. METHODS Two hundred and forty-six end-stage renal disease (ESRD) patients on peritoneal dialysis and 183 control subjects, all of Chinese origin, were genotyped for the ACE insertion/deletion (I/D) and the AGT M235T gene polymorphisms. Left ventricular mass index (LVMi) and relative wall thickness were measured using echocardiography. RESULTS Prevalence of ACE DD and AGT TT genotype was 14% and 83%, respectively, in ESRD patients and did not differ significantly from controls. A total percentage of 95% of our patients had LVH (171 with concentric and 63 with eccentric hypertrophy). Adjusting for age, gender, body mass index, duration of dialysis, diabetes, renal diagnosis, hematocrit, systolic and diastolic blood pressure, dialysis urea clearance, residual glomerular filtration rate, and use of converting enzyme inhibitors or angiotensin receptor blockers, AGT TT genotype remained independently associated with greater LVMi (coefficient = 28.73; 95% CI, 5.72 to 51.75; P = 0.015) and relative wall thickness (coefficient = 0.072; 95% CI, 0.022 to 0.122; P = 0.005) than MT/MM genotypes. LVMi and relative wall thickness did not differ significantly among patients with DD, DI, and II genotypes. No statistical significant interaction was noted between ACE and AGT gene polymorphism in relation to LVMi and relative wall thickness. CONCLUSION Polymorphism of the AGT M235T gene but not ACE I/D gene is associated with greater LVMi and relative wall thickness, indicating more concentric LVH, in Chinese peritoneal dialysis patients. Possible synergistic effects between AGT and ACE gene polymorphism require further evaluation in a larger population.
Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis

Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS). Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms. Results: Two SCN10A polymorphisms in high linkage disequilibrium (r2 = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10−4; rs6801957: p = 0.0025). Patients with MS with rs6795970AA genotype performed significantly worse than rs6795970G carriers in MSFC (p = 1.8 × 10−4) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970AA carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A–genotype effect was observed on MSFC performance in healthy participants. Conclusions: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.
Prevalence of spondyloarthropathies in an Italian population sample: a regional community‐based study

Objective. To estimate the prevalence of spondyloarthropathies (SpA) in an adult population in Marche, a region located in central Italy. Methods. A cross‐sectional population‐based study was conducted on a target adult population of 20 882. Questionnaires were sent to a random sample of 3664 individuals aged 18 years and over, selected from the lists of 16 general practices. Trained rheumatologists carried out structured visits in which respondent subjects were asked about symptoms of back pain, peripheral arthritis, joint swelling, psoriasis, and the occurrence of diarrhoea and dysuria. A family history of rheumatic disease, psoriasis, or uveitis was assessed. Cases were further classified as ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel disease (IBD)‐associated arthritis, and undifferentiated SpA by the European Spondyloarthropathy Study Group (ESSG) criteria. Results. A total of 2155 subjects participated to the study (response rate 58.8%). Twenty‐three cases of SpA (18 men, five women, mean age 48.3 ± 12.1 years) were confirmed, with an overall prevalence of 1.06% [95% confidence interval (CI) 0.78–1.38]. The most common SpA was PsA, with a prevalence of 0.42% (95% CI 0.31–0.61), followed by AS with 0.37% (95% CI 0.23–0.49). Two cases with undifferentiated SpA, two with ReA, and two with IBD‐associated arthritis were also observed (0.09%, 95% CI 0.04–0.16). Conclusions. This is the first population‐based study that provides an estimate of the prevalence of SpA in Italy. PsA and AS were the most common SpA subsets. Further epidemiological studies are needed to obtain reliable prevalence rates and to better understand our findings.
Phenotypic Switching in a Cryptococcus neoformans Variety gattii Strain Is Associated with Changes in Virulence and Promotes Dissemination to the Central Nervous System

ABSTRACT This is the first report of a Cryptococcus neoformans var. gattii strain (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var. grubii and C. neoformans var. neoformans strains, the switch is associated with changes in the polysaccharide capsule and virulence in animal models. In murine infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021). In contrast to the serotype A and D strains, the serotype B strain switches in vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular survival in macrophages. Consistent with this finding, switching to the mucoid variant is observed in pulmonary infection with NP1-SM. In contrast, the thin polysaccharide capsule of NP1-SM permits better crossing of the blood-brain barrier. In this regard, only smooth colonies were grown from brain homogenates of NP1-MC-infected mice. Our findings have important implications for the pathogenesis of cryptococcosis and suggest that phenotypic switching affects host-pathogen interactions in the local microenvironment. This altered interaction then selects for specific colony variants to arise in a pathogen population.
Predicting percentage of retail yield from carcass measurements, the yield grading equation, and closely trimmed, boxed beef weights.

Over the past 3 yr, 100 carcasses (64 steers, 24 bulls, and 12 heifers) were fabricated into closely trimmed (6 mm maximum fat cover), boxed beef and further evaluated for percentage of retail yield at the Iowa State University Meat Laboratory. Hot carcass weight ranged from 235 to 399 kg with a least squares mean (LSM) and standard error across all sex classes of 318 +/- 3 kg. Additionally, fat cover ranged from . 30 to 1.78 cm with an average of . 91 +/- . 05 cm. The LSM for longissimus muscle area (LMA) across all sex classes was 81.6 +/- 1.0 cm2. Bulls had significantly less subcutaneous fat (P less than .01) and greater LMA (P less than .01) than did either steers or heifers. Retail yield from the boxed chuck, expressed as a percentage of cold carcass weight, was 19.2 for bulls and 14.8 for steers. This difference was due primarily to a reduction of intermuscular fat. Similarly, bulls had a greater yield (P less than .01) of the boxed round than did steers. When cattle of differing frame sizes were compared, only percentage of retail yield of the boxed round was significant (P less than .01): large-framed cattle yielded 14.3 +/- . 2%, compared with 12.8 +/- . 2% for the small-framed cattle. When all possible regression analyses were run, sex class differences accounted for 25.7% of the variation in retail yield. The current USDA retail yield equation accounted for only 37.2% of the variation. Percentage of closely trimmed, boneless round had an R2-value of . 57. (ABSTRACT TRUNCATED AT 250 WORDS)
The unfolding illness trajectory of stroke

Purpose: To describe the characteristics of the illness trajectory of stroke during the first year. Method: A qualitative, prospective case study design; repeated in-depth semi-structured interviews with nine mild to moderately affected stroke patients during the course of the first year. A total of 63 interviews were conducted. The interview data were transcribed verbatim and analysed as a text, using a hermeneutic approach. Results: A stroke is not necessarily experienced as an abrupt psychosocial crisis by the stroke patient. The adjustment process seems to be gradually evolving and prolonged over most of the first year following the cerebro-vascular accident (CVA). The illness trajectory may be divided into four phases, each with characteristic tasks and focal points. The adjustment process involves hard physical and psychosocial work on the part of patient. A necessary pre-requisite for adjustment is a realistic conception of the illness and its implications. This takes time and experience to achieve. Conclusions: The adjustment process following stroke is gradual and prolonged. In order to move away from the predominant functional rehabilitation approach towards a more comprehensive and better targeted service, increased understanding of the complexities of the adjustment process is necessary.
Oligomerization and dissociation of AP-1 adaptors are regulated by cargo signals and by ArfGAP1-induced GTP hydrolysis.

The mechanism of AP-1/clathrin coat formation was analyzed using purified adaptor proteins and synthetic liposomes presenting tyrosine sorting signals. AP-1 adaptors recruited in the presence of Arf1.GTP and sorting signals were found to oligomerize to high-molecular-weight complexes even in the absence of clathrin. The appendage domains of the AP-1 adaptins were not required for oligomerization. On GTP hydrolysis induced by the GTPase-activating protein ArfGAP1, the complexes were disassembled and AP-1 dissociated from the membrane. AP-1 stimulated ArfGAP1 activity, suggesting a role of AP-1 in the regulation of the Arf1 "GTPase timer. " In the presence of cytosol, AP-1 could be recruited to liposomes without sorting signals, consistent with the existence of docking factors in the cytosol. Under these conditions, however, AP-1 remained monomeric, and recruitment in the presence of GTP was short-lived. Sorting signals allowed stable recruitment and oligomerization also in the presence of cytosol. These results suggest a mechanism whereby initial assembly of AP-1 with Arf1.GTP and ArfGAP1 on the membrane stimulates Arf1 GTPase activity, whereas interaction with cargo induces oligomerization and reduces the rate of GTP hydrolysis, thus contributing to efficient cargo sorting.
End User Security and Privacy Concerns with Smart Homes

The Internet of Things is becoming increasingly widespread in home environments. Consumers are transforming their homes into smart homes, with internet-connected sensors, lights, appliances, and locks, controlled by voice or other user-deﬁned automations. Security experts have identiﬁed concerns with IoT and smart homes, including privacy risks as well as vulnerable and unreliable devices. These concerns are supported by recent high proﬁle attacks, such as the Mirai DDoS attacks. However, little work has studied the security and privacy concerns of end users who actually set up and interact with today’s smart homes. To bridge this gap, we conduct semi-structured interviews with ﬁfteen people living in smart homes (twelve smart home administrators and three other residents) to learn about how they use their smart homes, and to understand their security and privacy related attitudes, expectations, and actions. Among other ﬁndings, we identify gaps in threat models arising from limited technical understanding of smart homes, awareness of some security issues but limited concern, ad hoc mitigation strategies, and a mismatch between the concerns and power of the smart home administrator and other people in the home. From these and other ﬁndings, we distill recommendations for smart home technology designers and future research.
Brian Balogh, Chain Reaction: Expert Debate and Public Participation in American commercial nuclear power, 1945-1975

milieu des années 1870 une multinationale, car, si les sociétés menaient en commun la recherche et le développement de produits, il n'y avait pas d'action commerciale harmonisée, mais plutôt une sévère concurrence, comme entre les sociétés britannique et allemande. En revanche la Nobel Dynamite Trust Company, fondée en 1886, la première holding du monde, est une véritable multinationale. Il y a ici innovation de structure, à une époque où les formes de capitalisme familial parvenaient encore à une convergence comparable des stratégies en multipliant les maisons parentes (on pourra évoquer les crayons Faber, ou les inévitables Rothschild). L'auteur conclut par une bonne remarque. A une époque où les nationalismes n'avaient pas encore complètement transformé les schèmes de la pensée, un industriel ou un banquier n'avait pas de raison de s'interroger sur le bien-fondé d'une structure internationale de production, car aucun motif ne pouvait le conduire à limiter ses affaires aux frontières nationales, fût-il fabricant d'explosifs. Cette étude nous montre aussi que Nobel qui avait la majorité des actions dans plusieurs des sociétés, n'était pas parvenu à les organiser et à les unifier ; et que lorsqu'il y parvient, il a moins de 6% des actions dans ses sociétés, sauf dans la Nobel britannique dont il détient 25 %. Le pouvoir n'est pas directement lié à la propriété du capital social. Kersti Ullenhag se situe, elle aussi, dans une problématique chandlerienne. Elle analyse les raisons des fusions bancaires dans les années 1970 et 1980 en Suède et se demande qui sont les agents actifs : propriétaires ou managers ? Elle montre que les fusions ont été suscitées par les propriétaires qui détiennent alors le pouvoir, qu'elles ont correspondu à la recherche de nouvelles opportunités dans un marché transformé par la dérégulation et les nouvelles techniques, et, donc, qu'en fin de compte le processus de concentration a été induit par les politiques qui ont modifié la législation. Les innovateurs auraient-ils moins été les entrepreneurs que les membres du Parlement? On lui répondra que, sans que l'on puisse lui refuser une certaine autonomie, la décision politique est aussi la résultante des pressions contradictoires des différents groupes sociaux et professionnels.
Classification of extracellularly recorded neurons by their discharge patterns and their correlates with intracellularly identified neuronal types in the frontal cortex of behaving monkeys

Neurons in the cerebral cortex are not homogeneous. However, neuronal types have been ignored in most previous work studying neuronal processes in behaving monkeys. We propose a new method to identify neuronal types in extracellular recording studies of behaving monkeys. We classified neurons as either bursting or non‐bursting, and then classified the bursting neurons into three types: (i) neurons displaying a burst of many spikes (maximum number of spikes within a burst; NSB max ≥ 8) at a high discharge rate (maximum interspike interval; ISI max < 5 ms); (ii) neurons displaying a burst of fewer spikes (NSB max ≤ 5) at a high discharge rate (ISI max < 5 ms); and (iii) neurons displaying a burst of a few spikes (NSB max ≤ 7) at relatively long ISIs (ISI max > 5 ms). We found that the discharge patterns of the four groups corresponded to those of regular spiking (RS), fast spiking (FS), fast rhythmic bursting (FRB) and intrinsic bursting (IB) neurons demonstrated in intracellular recording studies using in vitro slice preparations, respectively. In addition, we examined correlations with the task events for neurons recorded in the frontal eye field and neuronal interactions for pairs of neurons recorded simultaneously from a single electrode. We found that they were substantially different between RS and FS types. These results suggest that neurons in the frontal cortex of behaving monkeys can be classified into four types based on their discharge patterns, and that these four types contribute differentially to cortical operations.
Left Ventricular Outflow Tract Obstruction Associated with Chronic Ventricular Assist Device Support

Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63–1,339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.