Introduction to Postgraduate Pedagogies: Centring Graduate Teaching Assistants in Higher Education

Across the United Kingdom (UK) and beyond, Graduate Teaching Assistants (GTAs) are an integral part of universities and a substantial part of the Higher Education workforce. While there is a growing body of scholarship about the role of the GTA, and texts and materials which seek to support them as they carry out their responsibilities, the voice of GTAs themselves is less often heard and there exists no systematic account of their perspectives, experiences and contributions. This open-access journal aims to help fill this gap by bringing to the fore GTA voices and experiences. Based on the firm belief that GTAs bring important and potentially unique skills, ideas and approaches to lecture halls, labs and seminar rooms, it includes contributions from current or recent GTAs, and those working with them. Postgraduate Pedagogies aims to synthesise and analyse, reflect on and assert the unique experiences of GTAs, the contributions they bring to the Higher Education (HE) teaching and learning environment, and the specific challenges they face

Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping [preprint]

The timing of DNA replication is largely regulated by the location and timing of replication origin firing. Therefore, much effort has been invested in identifying and analyzing human replication origins. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual origins in metazoans has made mapping the location and timing of replication initiation in human cells difficult. We have mapped early-firing origins in HeLa cells using Optical Replication Mapping, a high-throughput single-molecule approach based on Bionano Genomics genomic mapping technology. The single-molecule nature and 290-fold coverage of our dataset allowed us to identify origins that fire with as little as 1% efficiency. We find sites of human replication initiation in early S phase are not confined to well-defined efficient replication origins, but are instead distributed across broad initiation zones consisting of many inefficient origins. These early-firing initiation zones co-localize with initiation zones inferred from Okazaki-fragment-mapping analysis and are enriched in ORC1 binding sites. Although most early-firing origins fire in early-replication regions of the genome, a significant number fire in late-replicating regions, suggesting that the major difference between origins in early and late replicating regions is their probability of firing in early S-phase, as opposed to qualitative differences in their firing-time distributions. This observation is consistent with stochastic models of origin timing regulation, which explain the regulation of replication timing in yeast

BioNano genome mapping of individual chromosomes supports physical mapping and sequence assembly in complex plant genomes

The assembly of a reference genome sequence of bread wheat is challenging due to its specific features such as the genome size of 17 Gbp, polyploid nature and prevalence of repetitive sequences. BAC-by-BAC sequencing based on chromosomal physical maps, adopted by the International Wheat Genome Sequencing Consortium as the key strategy, reduces problems caused by the genome complexity and polyploidy, but the repeat content still hampers the sequence assembly. Availability of a high-resolution genomic map to guide sequence scaffolding and validate physical map and sequence assemblies would be highly beneficial to obtaining an accurate and complete genome sequence. Here, we chose the short arm of chromosome 7D (7DS) as a model to demonstrate for the first time that it is possible to couple chromosome flow sorting with genome mapping in nanochannel arrays and create a de novo genome map of a wheat chromosome. We constructed a high-resolution chromosome map composed of 371 contigs with an N50 of 1.3 Mb. Long DNA molecules achieved by our approach facilitated chromosome-scale analysis of repetitive sequences and revealed a ~800-kb array of tandem repeats intractable to current DNA sequencing technologies. Anchoring 7DS sequence assemblies obtained by clone-by-clone sequencing to the 7DS genome map provided a valuable tool to improve the BAC-contig physical map and validate sequence assembly on a chromosome-arm scale. Our results indicate that creating genome maps for the whole wheat genome in a chromosome-by-chromosome manner is feasible and that they will be an affordable tool to support the production of improved pseudomolecules

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Rare Dravet-like epileptic encephalopathy with a novel mutation of PCDH19 gene

Mutacija gena PCDH19, koji kodira protokaderin 19 na kromosomu Xq22, rezultira epilepičkim sindromom s početkom napadaja u dojenačkoj dobi, s blagim do teškim intelektualnim oštećenjem i autističnim obilježjima ili bez njih. Ovaj poremećaj pokazuje neobičan obrazac X- vezanog nasljeđivanja, koji zahvaća heterozigotne žene, ali štedi hemizigotne muškarce. Smatra se da se temeljni odgovorni mehanizam odnosi na „celularnu interferenciju“. Postoji široki klinički spektar napadaja, uglavnom s početkom u dojenačkom ili ranom dječjem razdoblju. Dio bolesnika pokazuje fenotip nalik na sindrom Dravet. Napadaji se uglavnom javljaju u kratkim serijama, već kod blago do umjereno povišene tjelesne temperature. U početnoj fazi primjena antiepileptičkih lijekova relativno slabo utječe na smanjenje napadaja. No s napredovanjem bolesti, učestalost napadaja i njihova farmakorezistencija opadaju. Mogu se javiti smetnje ponašanja, kao što su autistična, opsesivna ili agresivna obilježja. Prikazana je devetogodišnja djevojčica koja od rane dječje dobi boluje i liječi se od farmakorezistentne epilepsije, koja se klinički prezentirala serijom žarišnih motoričkih napadaja praćenih strahom i vrištanjem. Ponavljani interiktalni i iktalni elektroencefalogrami, u budnosti i spavanju, bili su bez specifi čnih abnormalnosti, kao i slikovni prikaz mozga magnetskom rezonancijom visoke rezolucije (3T). Analizom cerebrospinalnog likvora isključene su upalne bolesti središnjeg živčanog sustava, a opsežnom metaboličkom obradom rijetke bolesti s epileptičkim napadajima. Nakon prvih napadaja preporučen je fenobarbiton, a nakon recidiviranja bila je na terapiji s više kombinacija različitih antiepileptika i nijedna nije bila učinkovita. Potpuna kontrola napadaja nikad nije postignuta. Genskom analizom pronađena je nova heterozigotna nonsense mutacija (c.1630C>T;p. Q544X) u egzonu 1 gena PCDH 19 na Xq22.1. U terapiju je uključen perampanel uz valproat i levetiracetam. Željeli smo upozoriti na rijedak oblik epileptičke encefalopatije od koje obolijevaju samo ženska djeca i na koju treba obratiti pozornost u diferencijalnoj dijagnozi nekontroliranih epileptičkih sindroma vezanih za febrilna stanja.Mutation in PCDH 19 gene, encoding prothocadherin 19 on chromosome Xq22, results in an epileptic syndrome with seizure onset in infancy, with or without mild to severe intellectual impairment or autistic features. This disorder demonstrates an unusual pattern of X-linked inheritance, aff ecting heterozygous female but sparing hemizygous male individuals. The underlying responsible mechanism is considered to be a ‘cellular interference’. There is a wide clinical spectrum of seizures, generally starting in infancy or early childhood. A portion of patients manifest a phenotype resembling Dravet syndrome. The seizures mostly occur in brief clusters even at mild to moderately elevated temperature. In the initial course of the disease, the seizures become relatively resistant to antiepileptic drugs. However, as the disease progresses, the frequency of seizures and their pharmacoresistance tend to decrease. There may be behavioral diffi culties such as autistic, obsessive or aggressive features. The aim of this paper is to describe clinical features and unusual way of inheritance of PCDH19 gene related epilepsy in a 10-year-old girl, with special reference to early disease characteristics and treatment effi cacy. From early childhood, this 10-year-old girl suff ered from and was treated for resistant epilepsy, clinically presenting with a series of focal motor seizures accompanied by fear and screaming. On many occasions, repeated interictal waking and sleeping EEGs, as well as high resolution brain MRI (3T) were normal. Analysis of cerebrospinal fl uid excluded infl ammatory diseases of the central nervous system. Rare metabolic diseases with epileptic seizures were excluded by metabolic tests. After the fi rst seizure, phenobarbital was recommended, and after recurrence she received therapy with multiple combinations of various antiepileptic drugs, none of which was eff ective. Complete seizure control was never achieved. Genetic analysis revealed novel heterozigous nonsence mutation (c.1630C>T;p. Q544X) in exon 1 of PCDH19 gene on Xq22.1. Therapy included perampanel with valproate and levetiracetam. The authors want to warn of this rare form of epileptic encephalopathy that aff ects only female children and to emphasize its importance in the diff erential diagnosis of uncontrolled epileptic syndromes associated with febrile conditions