A review of diagnostic and functional imaging in headache

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache — the posterior hypothalamic grey matter — and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Inelastic bending of beams under time-varing moments: a state variable approach

The inelastic response of a beam to several time-varying moments is presented. The constitutive equations used to describe the beam material are due to Hart. This is one of several state variable theories of inelastic deformation that have been proposed recently. Hart's equations have been previously shown to accurately predict the response of uniaxial specimens to time-varying loads. It is seen that Hart's theory is able to qualitatively simulate various phenomena in creep and plasticity such as the effect of previous deformation history, yielding, strain recovery, material hardening and strain rate sensitivity in this case of bending of a beam. The computational scheme used to integrate the equations is very efficient

Typing Mlo alleles for powdery mildew resistance in barley by single nucleotide polymorphism analysis using MALDI-ToF mass spectrometry

Single nucleotide polymorphisms (SNPs) have been identified in a range of plant genomes. Development of rapid, low-cost methods to enable their validation and implementation as molecular markers is now required for practical applications. We report the development of single and multi-nucleotide primer extension assays to genotype co-dominant SNPs from small quantities of barley leaf tissue. In the single nucleotide primer extension assay, a genotyping primer with its 3′ end directly flanking a SNP was annealed to a target sequence and extended by a single dideoxynucleotide triphosphate complementary to the polymorphic base. In the multi-nucleotide primer extension assay, designed to facilitate allele calling, the genotyping primer with its 3′ end flanking the SNP was extended by either 1 or 2 nucleotides, depending on the allele encountered. Extension products were analysed using MALDI-ToF mass spectrometry and, making use of the molecular weight difference between DNA bases, the incorporated nucleotides were identified by the increase in mass of the extended primers. Based on a SNP identified in the barley Mlo gene, primer extension assays were designed and used for co-dominant marker-assisted selection of barley seedlings segregating for mlo-mediated resistance to powdery mildew. This allowed accurate selection of progeny lines carrying alleles for resistance to powdery mildew, including heterozygotes. Doubled haploid barley progenies were screened for Mlo alleles and a complete correlation between mlo/mlo genotype and resistant phenotype was found The method has been used by barley breeders for routine selection of barley genotypes resistant to powdery mildew

Stable isotope mixing models elucidate sex and size effects on the diet of a generalist marine predator

We applied a 2-step clustering algorithm and Bayesian stable isotope mixing model to examine intraspecific differences in the contribution of prey sources to the diet and foraging habitat of harbor seals Phoca vitulina in the Salish Sea, USA. We analyzed stable isotopes of carbon and nitrogen collected from 32 seals and 248 prey samples representing 18 of 25 of the most common seal prey items identified in seal scat. Stable isotope analyses identified significant harbor seal sex- and size-based differences in diet and foraging habitat use. In comparison to males, female harbor seals had a higher contribution of prey items that were more 13C-enriched. This result may indicate that females derived more of their δ13C value from nearshore versus offshore food webs, an explanation supported by movement data on this population. However, large seals of both sexes displayed a greater offshore signal in their diet, indicating that seal mass effects on foraging habitat use were somewhat independent of sex. Our work contributes to understanding trophic linkages between these generalist consumers and their prey. The foraging differences that we detected between male and female harbor seals present complex challenges for fisheries management and for the design of marine reserves. Many marine reserves in the Pacific Northwest are located in close proximity to seal haul-out sites. By lowering the energetic costs of foraging of females, these reserves may ultimately have the unintended effect of increasing individual fitness, population growth rate, and influencing future predator-induced mortality on endangered species