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Parchment represents an invaluable cultural reservoir. Retrieving an additional layer of information from these abundant, dated livestock-skins via the use of ancient DNA (aDNA) sequencing has been mooted by a number of researchers. However, prior PCR-based work has indicated that this may be challenged by cross-individual and cross-species contamination, perhaps from the bulk parchment preparation process. Here we apply next generation sequencing to two parchments of seventeenth and eighteenth century northern English provenance. Following alignment to the published sheep, goat, cow and human genomes, it is clear that the only genome displaying substantial unique homology is sheep and this species identification is confirmed by collagen peptide mass spectrometry. Only 4% of sequence reads align preferentially to a different species indicating low contamination across species. Moreover, mitochondrial DNA sequences suggest an upper bound of contamination at 5%. Over 45% of reads aligned to the sheep genome, and even this limited sequencing exercise yield 9 and 7% of each sampled sheep genome post filtering, allowing the mapping of genetic affinity to modern British sheep breeds. We conclude that parchment represents an excellent substrate for genomic analyses of historical livestock.

Parchment represents an invaluable cultural reservoir. Retrieving an additional layer of information from these abundant, dated livestock-skins via the use of ancient DNA (aDNA) sequencing has been mooted by a number of researchers. However, prior PCR-based work has indicated that this may be challenged by cross-individual and cross-species contamination, perhaps from the bulk parchment preparation process. Here we apply next generation sequencing to two parchments of seventeenth and eighteenth century northern English provenance. Following alignment to the published sheep, goat, cow and human genomes, it is clear that the only genome displaying substantial unique homology is sheep and this species identification is confirmed by collagen peptide mass spectrometry. Only 4% of sequence reads align preferentially to a different species indicating low contamination across species. Moreover, mitochondrial DNA sequences suggest an upper bound of contamination at 5%. Over 45% of reads aligned to the sheep genome, and even this limited sequencing exercise yield 9 and 7% of each sampled sheep genome post filtering, allowing the mapping of genetic affinity to modern British sheep breeds. We conclude that parchment represents an excellent substrate for genomic analyses of historical livestock.

The microtubules, neurofilaments and microfilaments of the neuronal cytoskeleton are essential for the normal functioning of the neurone. Recent studies have shown that disruption of the cytoskeleton may represent a final pathway in many types of neuronal cell injury with both the somato-dendritic and axonal cytoskeleton being affected. This review discusses the current evidence on the role of the neuronal cytoskeleton in the pathogenesis of traumatic brain damage.

Field experiments were conducted from 1989 to 1992 to determine whether no-tillage corn grown in 38-cm rows and a 2× population could improve weed control relative to 76-cm rows and 1× population under reduced-herbicide options. A standard treatment including 1.12 kg ai/ha of atrazine plus 2.24 kg ai/ha of metolachlor was compared with a treatment including the same herbicides applied at 25% of the standard rates. Both treatments included 0.56 kg ai/ha of paraquat which controlled annual weeds established at the time of application. Weed control was less in the 25%-herbicide treatment than in the standard treatment in two of four years when corn was grown in 76-cm rows with a 1× population. The 25%-herbicide treatment provided weed control and grain yields similar to the standard treatment in each year when corn was grown in 38-cm rows with a 2× population. Weed control was poor and yield was reduced when no herbicides were applied regardless of row spacing or population. The leaf canopy of corn in the 38-cm row/2×-population treatment reduced light transmittance 1 wk earlier than corn in the 76-cm row/1×-population treatment.

Research was conducted to determine the optimum population and row spacing for corn production and for suppressing velvetleaf growth and seed production. Corn was grown in a factorial arrangement of three populations targeted at 64,000 (1 ×), 96,000 (1.5 ×), or 128,000 (2 ×) plants ha−1 and two row spacings of 38 or 76 cm. Influences on corn were determined in weed-free plots, and influences on velvetleaf were determined for target plants established at 1.5–m intervals along the center of corn interrows. Four velvetleaf plantings were made at weekly intervals beginning at corn planting. Corn row spacing had little influence on corn or velvetleaf. Corn yield exhibited a parabolic response to population with a maximum of approximately 90,000 plants ha−1 in one year, no response to population in another year, and a linear decline with increasing population in a dry year. Velvetleaf seed production was reduced 69 to 94% by the 1.5 × population and 99% by the 2 × population compared to the standard 1 × population when velvetleaf emerged with corn. Velvetleaf seed production was eliminated when velvetleaf emerged at or later than corn leaf stages 3, 5, and 6 for corn populations of 2 ×, 1.5 ×, and 1 ×, respectively. Reduced velvetleaf seed production was correlated with lower positioning of plants in the corn canopy and reduced light availability. Results suggest that higher corn populations could aid integrated weed management strategies by reducing seed production and limiting the build-up of weed populations.

In a trial comparing decompressive craniectomy with medical therapy in patients with traumatic brain injury and raised intracranial pressure refractory to medical therapy, decompressive craniectomy resulted in lower mortality and higher rates of vegetative state and severe disability. After traumatic brain injury (TBI), intracranial pressure can be elevated owing to a mass effect from intracranial hematomas, contusions, diffuse brain swelling, or hydrocephalus. 1 Intracranial hypertension can lead to brain ischemia by reducing the cerebral perfusion pressure. 2 Intracranial hypertension after TBI is associated with an increased risk of death in most studies. 3 , 4 The monitoring of intracranial pressure and the administration of interventions to lower intracranial pressure are routinely used in patients with TBI, despite the lack of level 1 evidence. 5 Decompressive craniectomy is a surgical procedure in which a large section of the skull is removed and the underlying . . .

Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes 1 – 3 . Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders 4 – 7 . How retromer is assembled and how it is recruited to form coated tubules is not known. Here we describe the structure of the retromer complex (Vps26–Vps29–Vps35) assembled on membrane tubules with the bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo-electron tomography and subtomogram averaging. This reveals a membrane-associated Vps5 array, from which arches of retromer extend away from the membrane surface. Vps35 forms the ‘legs’ of these arches, and Vps29 resides at the apex where it is free to interact with regulatory factors. The bases of the arches connect to each other and to Vps5 through Vps26, and the presence of the same arches on coated tubules within cells confirms their functional importance. Vps5 binds to Vps26 at a position analogous to the previously described cargo- and Snx3-binding site, which suggests the existence of distinct retromer-sorting nexin assemblies. The structure provides insight into the architecture of the coat and its mechanism of assembly, and suggests that retromer promotes tubule formation by directing the distribution of sorting nexin proteins on the membrane surface while providing a scaffold for regulatory-protein interactions. The retromer complex (the vacuolar protein sorting heterotrimer Vps26–Vps29–Vps35) has been resolved in association with membranes and the sorting nexin protein Vps5 using cryo-electron tomography.

Brucella melitensis is a major livestock bacterial pathogen and zoonosis, causing disease and infection-related abortions in small ruminants and humans. A considerable burden to animal-based economies today, the presence of Brucella in Neolithic pastoral communities has been hypothesised but we lack direct genomic evidence thus far. We report a 3.45X B. melitensis genome preserved in an ~8000 year old sheep specimen from Menteşe Höyük, Northwest Türkiye, demonstrating that the pathogen had evolved and was circulating in Neolithic livestock. The genome is basal with respect to all known B. melitensis and allows the calibration of the B. melitensis speciation time from the primarily cattle-infecting B. abortus to approximately 9800 years Before Present (BP), coinciding with a period of consolidation and dispersal of livestock economies. We use the basal genome to timestamp evolutionary events in B. melitensis , including pseudogenization events linked to erythritol response, the supposed determinant of the pathogen’s placental tropism in goats and sheep. Our data suggest that the development of herd management and multi-species livestock economies in the 11 th –9 th millennium BP drove speciation and host adaptation of this zoonotic pathogen. Brucella melitensis is a zoonotic bacterial pathogen of livestock that can infect humans and causes brucellosis. Here, the authors sequence an ancient specimen of B. melitensis and show that the species emerged in the Neolithic period, around the time of development of animal management practices.

The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

Since 1974, the Glasgow Coma Scale has provided a practical method for bedside assessment of impairment of conscious level, the clinical hallmark of acute brain injury. The scale was designed to be easy to use in clinical practice in general and specialist units and to replace previous ill-defined and inconsistent methods. 40 years later, the Glasgow Coma Scale has become an integral part of clinical practice and research worldwide. Findings using the scale have shown strong associations with those obtained by use of other early indices of severity and outcome. However, predictive statements should only be made in combination with other variables in a multivariate model. Individual patients are best described by the three components of the coma scale; whereas the derived total coma score should be used to characterise groups. Adherence to this principle and enhancement of the reliable practical use of the scale through continuing education of health professionals, standardisation across different settings, and consensus on methods to address confounders will maintain its role in clinical practice and research in the future.