Various commonly used organic solvents were dried with several different drying agents. A glovebox-bound coulometric Karl Fischer apparatus with a two-compartment measuring cell was used to determine ...the efficiency of the drying process. Recommendations are made relating to optimum drying agents/conditions that can be used to rapidly and reliably generate solvents with low residual water content by means of commonly available materials found in most synthesis laboratories. The practical method provides for safer handling and drying of solvents than methods calling for the use of reactive metals, metal hydrides, or solvent distillation.
The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity ...in major depression, a relationship of HPA axis activity to cognitive performance and a potential role of HPA axis genetic variation in cognition. The present study investigated the simultaneous roles HPA axis activity, clinical symptomatology and HPA genetic variation play in cognitive performance. Patients with major depression with psychotic major depression (PMD) and with nonpsychotic major depression (NPMD) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, overnight hourly blood sampling for cortisol and genetic assessment. Cognitive performance differed as a function of depression subtype. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher cortisol than did NPMDs and HCs. Cortisol, clinical symptoms and variation in genes, NR3C1 (glucocorticoid receptor; GR) and NR3C2 (mineralocorticoid receptor; MR) that encode for GRs and MRs, predicted cognitive performance. Beyond the effects of cortisol, demographics and clinical symptoms, NR3C1 variation predicted attention and working memory, whereas NR3C2 polymorphisms predicted memory performance. These findings parallel the distribution of GR and MR in primate brain and their putative roles in specific cognitive tasks. HPA axis genetic variation and activity were important predictors of cognition across the entire sample of depressed subjects and HR. GR and MR genetic variation predicted unique cognitive functions, beyond the influence of cortisol and clinical symptoms. GR genetic variation was implicated in attention and working memory, whereas MR was implicated in verbal memory.
For over 100 years, thyroid hormones have been known to be essential for neonatal neurodevelopment but whether they are required by the foetal brain remains a matter of controversy. For decades, the ...prevailing view was that thyroid hormones are not necessary until after birth because circulating levels in the foetus are very low and the placenta forms an efficient barrier to their transfer from the mother. Clinical observations of good neurological outcome following early treatment of congenital hypothyroidism were used to support the view that thyroid hormones are not required early in neurodevelopment. Nevertheless, the issue remained contentious because of findings that the severity of foetal neurological deficit due to maternal iodine deficiency correlated with the degree of maternal thyroxine (T4) deficiency. Furthermore, neurological damage in these cases could be prevented by correction of maternal T4 deficiency before mid‐gestation. This observation led to the opposing view, supported by epidemiological studies of neurological cretinism, that maternal thyroid hormones are important and necessary for early foetal neurodevelopment. It is now clear that thyroid hormones are essential for both foetal and post‐natal neurodevelopment and for the regulation of neuropsychological function in children and adults. In recent years, this controversial subject has progressed very rapidly following remarkable progress in understanding of the molecular mechanisms of thyroid hormone action. This article reviews the contributions of molecular biology and genetics to our new understanding of the physiological effects of thyroid hormones on neurodevelopment and in the adult brain.
Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we ...report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.
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•Deep dorsal horn neurons transiently express VGLUT3 and convey mechanical allodynia•They receive innocuous input and reside at the interface between touch and pain•Their local activation reveals a dorsally directed pathway for mechanical allodynia•Different microcircuits encode mechanical allodynia depending on the injury
Peirs et al. identified deep dorsal horn neurons that transiently express VGLUT3 and are required for mechanical allodynia. The neurons transmit innocuous input to dorsally directed pain microcircuits that are differentially engaged depending on the type of injury.
Population Dynamics and Control of Tuberculosis Dye, Christopher; Williams, Brian G
Science (American Association for the Advancement of Science),
05/2010, Letnik:
328, Številka:
5980
Journal Article
Recenzirano
More than 36 million patients have been successfully treated via the World Health Organization's strategy for tuberculosis (TB) control since 1995. Despite predictions of a decline in global ...incidence, the number of new cases continues to grow, approaching 10 million in 2010. Here we review the changing relationship between the causative agent, Mycobacterium tuberculosis, and its human host and examine a range of factors that could explain the persistence of TB. Although there are ways to reduce susceptibility to infection and disease, and a high-efficacy vaccine would boost TB prevention, early diagnosis and drug treatment to interrupt transmission remain the top priorities for control. Whatever the technology used, success depends critically on the social, institutional, and epidemiological context in which it is applied.
For centuries, humankind has constructed dams on rivers to control flooding, provide for irrigation and utilize potential energy for power, but generally dams had no or little provision for fish ...passage. Thus, they often blocked or impeded fish migrations. Empirical observations and “trial and error” approaches that characterized historical efforts to develop passage systems for upstream migrating fish often did not work. The first concerted efforts to develop scientifically based fishways for upstream migrant fish began in the early 1900s in Europe with field and laboratory testing of different fishway designs. These were followed by extensive efforts beginning in the 1940s in North America. Scientifically based testing of configurations for fishways for downstream migrant fish began in the 1950s. Nearly all early efforts were directed at salmonid species, with smaller efforts on shad. Recent species at risk legislation in the U.S.A., Canada, and Europe places renewed emphasis on fish passage for all migratory species, and efforts have also begun to develop successful passage strategies for migratory species in other countries worldwide. This has led to renewed efforts to develop effective passage systems and to try creative solutions using natural materials in addition to concrete or metal used in standard technical fishways. Regardless of the type of structures built, history has shown that the most effective means to develop successful installations has occurred when engineers and biologists worked together systematically to design passage structures based on the ability and willingness of fish to seek and accept the hydraulic conditions presented to them.
Abstract
The planetary and lunar ephemerides called DE440 and DE441 have been generated by fitting numerically integrated orbits to ground-based and space-based observations. Compared to the previous ...general-purpose ephemerides DE430, seven years of new data have been added to compute DE440 and DE441, with improved dynamical models and data calibration. The orbit of Jupiter has improved substantially by fitting to the Juno radio range and Very Long Baseline Array (VLBA) data of the Juno spacecraft. The orbit of Saturn has been improved by radio range and VLBA data of the Cassini spacecraft, with improved estimation of the spacecraft orbit. The orbit of Pluto has been improved from use of stellar occultation data reduced against the Gaia star catalog. The ephemerides DE440 and DE441 are fit to the same data set, but DE441 assumes no damping between the lunar liquid core and the solid mantle, which avoids a divergence when integrated backward in time. Therefore, DE441 is less accurate than DE440 for the current century, but covers a much longer duration of years −13,200 to +17,191, compared to DE440 covering years 1550–2650.
There have been no comprehensive reviews of the relation of breakfast cereal consumption to nutrition and health. This systematic review of all articles on breakfast cereals to October 2013 in the ...Scopus and Medline databases identified 232 articles with outcomes related to nutrient intake, weight, diabetes, cardiovascular disease, hypertension, digestive health, dental and mental health, and cognition. Sufficient evidence was available to develop 21 summary evidence statements, ranked from A (can be trusted to guide practice) to D (weak and must be applied with caution). Breakfast cereal consumption is associated with diets higher in vitamins and minerals and lower in fat (grade B) but is not associated with increased intakes of total energy or sodium (grade C) or risk of dental caries (grade B). Most studies on the nutritional impact are cross-sectional, with very few intervention studies, so breakfast cereal consumption may be a marker of an overall healthy lifestyle. Oat-, barley-, or psyllium-based cereals can help lower cholesterol concentrations (grade A), and high-fiber, wheat-based cereals can improve bowel function (grade A). Regular breakfast cereal consumption is associated with a lower body mass index and less risk of being overweight or obese (grade B). Presweetened breakfast cereals do not increase the risk of overweight and obesity in children (grade C). Whole-grain or high-fiber breakfast cereals are associated with a lower risk of diabetes (grade B) and cardiovascular disease (grade C). There is emerging evidence of associations with feelings of greater well-being and a lower risk of hypertension (grade D), but more research is required.
Dopaminergic cell loss due to the accumulation of α-syn is a core feature of the pathogenesis of Parkinson disease. Neuroinflammation specifically induced by α-synuclein has been shown to exacerbate ...neurodegeneration, yet the role of central nervous system (CNS) resident macrophages in this process remains unclear. We found that a specific subset of CNS resident macrophages, border-associated macrophages (BAMs), play an essential role in mediating α-synuclein related neuroinflammation due to their unique role as the antigen presenting cells necessary to initiate a CD4 T cell response whereas the loss of MHCII antigen presentation on microglia had no effect on neuroinflammation. Furthermore, α-synuclein expression led to an expansion in border-associated macrophage numbers and a unique damage-associated activation state. Through a combinatorial approach of single-cell RNA sequencing and depletion experiments, we found that border-associated macrophages played an essential role in immune cell recruitment, infiltration, and antigen presentation. Furthermore, border-associated macrophages were identified in post-mortem PD brain in close proximity to T cells. These results point to a role for border-associated macrophages in mediating the pathogenesis of Parkinson disease through their role in the orchestration of the α-synuclein-mediated neuroinflammatory response.
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