Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization

KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma

Executive function abnormalities in pathological gamblers

Background: Pathological gambling (PG) is an impulse control disorder characterized by persistent and maladaptive gambling behaviors with disruptive consequences for familial, occupational and social functions. The pathophysiology of PG is still unclear, but it is hypothesized that it might include environmental factors coupled with a genetic vulnerability and dysfunctions of different neurotransmitters and selected brain areas. Our study aimed to evaluate a group of patients suffering from PG by means of some neuropsychological tests in order to explore the brain areas related to the disorder. Methods: Twenty outpatients (15 men, 5 women), with a diagnosis of PG according to DSM-IV criteria, were included in the study and evaluated with a battery of neuropsychological tests: the Wisconsin Card Sorting Test (WCST), the Wechsler Memory Scale revised (WMS-R) and the Verbal Associative Fluency Test (FAS). The results obtained in the patients were compared with normative values of matched healthy control subjects. Results: The PG patients showed alterations at the WCST only, in particular they had a great difficulty in finding alternative methods of problem-solving and showed a decrease, rather than an increase, in efficiency, as they progressed through the consecutive phases of the test. The mean scores of the other tests were within the normal range. Conclusion: Our findings showed that patients affected by PG, in spite of normal intellectual, linguistic and visual-spatial abilities, had abnormalities emerging from the WCST, in particular they could not learn from their mistakes and look for alternative solutions. Our results would seem to confirm an altered functioning of the prefrontal areas which might provoke a sort of cognitive "rigidity" that might predispose to the development of impulsive and/or compulsive behaviors, such as those typical of PG. © 2008 Marazziti et al; licensee BioMed Central Ltd

The Challenges in Teaching English Online to Young Learners: Teachers’ Voices

Teaching and learning activities had shifted to online classes due to Covid-19 pandemic outbreaks. Hence,primary school teachers in Indonesia encountered several challenges with the unexpected changes inEnglish face-to-face classroom interaction to online learning with digital platforms. This study exploredthe challenges faced by four Indonesian EFL primary school teachers in implementing online learningand teachers’ solutions to the challenges. A qualitative study with a phenomenological approach was usedas the research design, and the data collection was obtained through observation and interview. Thisstudy showed that teachers found online English Language Teaching (ELT) activities more difficult thanface-to-face classrooms due to some challenges. The technical issue became the first challenge faced bythe teachers since both teachers and students needed an internet connection and device management.Secondly, most teachers found it difficult to implement various teaching methods in online learning. Theother reasons were that enhancing students’ engagement required more effort, and assessing students’English development took more work than in the face-to-face classroom. The implication of this researchis for teachers and students as it may help them address and generate new insights about the challengesand solutions in online classrooms. Furthermore, it highlights specific areas for future research

Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

Contains fulltext : 253170.pdf (Publisher’s version ) (Open Access

Influence of Myocardial Fibrosis on Left Ventricular Hypertrophy in Patients with Symptomatic Severe Aortic Stenosis.

Aim: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. Methods: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was 90 kdyn/cm(2) were considered to have non-physiologic hypertrophy. Results: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 \ub1 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. Conclusions: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload

The sorin freedom stentless pericardial valve: clinical and echocardiographic performance at 10 years.

Objective: The Sorin Pericarbon Freedom (SPF) is a stentless valve made of pericardium clinically available in 1990. We report the clinical and hemodynamic performance of the SPF at 10 years. Methods: From April 2000 to December 2005, 85 patients with a mean age of 75 \ub1 6 years (range 57-86), underwent aortic valve replacement (AVR) with an SPF. Mean left ventricular ejection fraction was 58 \ub1 10\% (range 29-86\%) and mean peak transvalvular gradient (PG) 86 \ub1 24 mmHg. Clinical evaluation was performed at 3, 6, 12 months, and yearly thereafter. Results: There were 2 operative deaths (2.4\%). Follow-up ranged from 2 to 135 months (mean 78 \ub1 32 months) and was 99\% complete. There were 35 late deaths, 7 of which were valve-related, with an actuarial survival of 45 \ub1 8\% at 10 years. Structural SPF deterioration occurred in 2 patients, with an actuarial freedom of 96 \ub1 3\%. A total of 4 patients were re-operated, 2 because of structural deterioration, 1 because of endocarditis, and 1 because of sinotubular junction dilatation; freedom from reoperation was 93 \ub1 4\% at 10 years. At last clinical control, 41 patients (89\%) were in NYHA class I or II. Mean SPF effective orifice area varied from 1.55 \ub1 0.66 cm2 for size 21 mm to 2.33 \ub1 0.86 cm2 for size 27 mm; PG varied from 19 \ub1 10 mmHg for size 21 mm to 11 \ub1 6 mmHg for size 27 mm. Left ventricular mass index decreased from 213 \ub1 51 gm/m2 to 157 \ub1 436 gm/m2 (p<0.001). Conclusions: The SPF has demonstrated overall good results in terms of valve durability and freedom from valve-related complications up to 10 years, with excellent hemodynamic performance

High prevalence of albuminuria amongst people who inject drugs: A cross-sectional study.

Albuminuria is a key biomarker for cardiovascular disease and chronic kidney disease. Our study aimed to describe the prevalence of albuminuria amongst people who inject drugs in London and to test any potential associations with demographic characteristics, past diagnoses, and drug preparation and administration practices. We carried out a cross-sectional survey amongst people who use drugs in London. The main outcome measure was any albuminuria including both microalbuminuria and macroalbuminuria. Three-hundred and sixteen samples were tested by local laboratory services. Our study initially employed point-of-care testing methods but this resulted in a high number of false positives. Our findings suggest the prevalence of albuminuria amongst PWID is twice that of the general population at 19% (95%CI 15.3-24.0%). Risk factors associated with albuminuria were HIV (aOR 4.11 [95% CI 1.37-12.38]); followed by overuse of acidifier for dissolving brown heroin prior to injection (aOR 2.10 [95% CI 1.04-4.22]). Albuminuria is high amongst people who inject drugs compared to the general population suggesting the presence of increased cardiovascular and renal pathologies. This is the first study to demonstrate an association with acidifier overuse. Dehydration may be common amongst this population and may affect the diagnostic accuracy of point-of-care testing for albuminuria

Common Scaling Patterns in Intertrade Times of U. S. Stocks

We analyze the sequence of time intervals between consecutive stock trades of thirty companies representing eight sectors of the U. S. economy over a period of four years. For all companies we find that: (i) the probability density function of intertrade times may be fit by a Weibull distribution; (ii) when appropriately rescaled the probability densities of all companies collapse onto a single curve implying a universal functional form; (iii) the intertrade times exhibit power-law correlated behavior within a trading day and a consistently greater degree of correlation over larger time scales, in agreement with the correlation behavior of the absolute price returns for the corresponding company, and (iv) the magnitude series of intertrade time increments is characterized by long-range power-law correlations suggesting the presence of nonlinear features in the trading dynamics, while the sign series is anti-correlated at small scales. Our results suggest that independent of industry sector, market capitalization and average level of trading activity, the series of intertrade times exhibit possibly universal scaling patterns, which may relate to a common mechanism underlying the trading dynamics of diverse companies. Further, our observation of long-range power-law correlations and a parallel with the crossover in the scaling of absolute price returns for each individual stock, support the hypothesis that the dynamics of transaction times may play a role in the process of price formation.Comment: 8 pages, 5 figures. Presented at The Second Nikkei Econophysics Workshop, Tokyo, 11-14 Nov. 2002. A subset appears in "The Application of Econophysics: Proceedings of the Second Nikkei Econophysics Symposium", editor H. Takayasu (Springer-Verlag, Tokyo, 2003) pp.51-57. Submitted to Phys. Rev. E on 25 June 200

Locating Photography

The specter of global dissemination haunted photography from its very beginning. This chapter explains two aspects of photography's “globalization”: its use as a “western” technique to document an increasingly colonized world and its dissemination around the world and its adoption by local practitioners. In rural and small‐town central India, the studio retains a central place in most people's encounters with photography. Martín Chambi would retain a lifelong adherence to the purity of the photographic image but other indigenista photographers, such as Juan Manuel Figueroa Aznar, would increasingly use paint alongside photography. A World System Photography, seen in networks that fold locally articulated practices into trajectories that fuse technics, history, and culture, can help people think in new ways about the “location” of photography. Locations have to be re‐imagined as “Terra Infirma”, unstable and complex positions which may have more of the quality of linking sections of a network than of territories