Inventory of ponds in the Norfolk Coast AONB - recommendations for pond survey and conservation

The banning of tributyltin (TBT) from boat antifouling paints in the late 1980s led to its replacement by alternative biocide additives (Voulvoulis et al., 2000; Marcheselli et al., 2010), including Cu (Dahl & Blanck, 1996) and Zn as active ingredients. It has been reported that Cu and Zn compounds associated with these biocides have caused substantial contamination of harbour and marina sediments (Eklund et al., 2010; Parks et al., 2010), with negative toxic consequences for aquatic organisms (Ytreberg et al., 2010). Indeed, it is evident that Cu and Zn compounds present in paint fragments are readily leached into the water column allowing entry into aquatic food webs (Jessop & Turner, 2011). Nevertheless, relatively little is known regarding antifoulant-derived metals contamination in freshwater lakes. The Norfolk and Suffolk Broads (Eastern England, UK) have been contaminated by antifoulant-derived heavy metals, particularly Cu and Zn which have increased since the banning of TBT (post-1987) in parts of the boated system (Boyle et al., in prep.). Further, recent studies suggest that current levels of sediment contamination by Cu may have negative ecological effects for aquatic ecosystems including inhibition of aquatic macrophyte germination and performance (Boyle et al., submitted; S. Lambert, unpublished data). In Hickling Broad (Thurne Broads system), post-TBT increases in Cu and Zn are also evident, with an interesting peak in Cu for the late 1990s in core HICK1 (Figure 1). This coincides with the large-scale loss of aquatic macrophytes (especially Characeae) from the lake in 1999 (Barker et al., 2008). HICK1 was collected in 2003. In the proposed study we sought to gain a fuller understanding of recent metal contamination in Hickling Broad up to the present day, whilst looking to verify and better contextualise the late 1990s Cu peak. Further, we aimed to determine whether the peak in Cu for Hickling Broad was also recorded at Horsey Mere which is used as a control site in this study i.e. is it just a Hickling phenomenon? Or is it a Thurne Broads system-wide effect

Cellular and clinical impact of Haploinsufficiency for genes involved in ATR signaling

Ataxia telangiectasia and Rad3-related (ATR) protein, a kinase that regulates a DNA damage-response pathway, is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay. Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly. Here, we examined ATR-pathway function in cell lines from three haploinsufficient contiguous gene-deletion disorders--a subset of blepharophimosis-ptosis-epicanthus inversus syndrome, Miller-Dieker lissencephaly syndrome, and Williams-Beuren syndrome--in which the deleted region encompasses ATR, RPA1, and RFC2, respectively. These three genes function in ATR signaling. Cell lines from these disorders displayed an impaired ATR-dependent DNA damage response. Thus, we describe ATR signaling as a pathway unusually sensitive to haploinsufficiency and identify three further human disorders displaying a defective ATR-dependent DNA damage response. The striking correlation of ATR-pathway dysfunction with the presence of microcephaly and growth delay strongly suggests a causal relationship

Evaluation of Preparation and Outcome of the Joint Admissions and Matriculation Board Examinations Among First Year Medical Students in Rivers State

Background: In most countries of the world, entrance into tertiary institution is regulated by statutory examining councils / bodies, after passing recommended examinations. The aim of this study was to evaluate the determinants of success at the Nigerian University Tertiary Matriculation Examination (UTME) among first year undergraduate medical students in Rivers State in the year 2022. Materials and Methods: A retrospective cross-sectional analytical study was carried out among first year undergraduate medical students in four universities. Data was collated and analysed using the Statistical Package for the Social Sciences (SPSS) version 20.0. Results: There were 219 (45.1%) males and 267 (54.9%) females, and their mean age was 19.45±2.80 years. Majority (n=372, 76.6%) of students prepared daily for at least 3-4 hours over at least 3 to 4 months (n=179, 36.8%) before passing their examinations. There were computer-related (134, 27.6%) and other issues. Only 257 (52.9%) students passed their UTME at first attempt. The number of UTME attempts reduces as average daily preparation hours increases; the higher the average daily examination preparation hours, the higher the chances of scoring above 200 in first attempt; the higher the number of months of active preparation, the lower the number of attempts at UTME; and these relationships were statistically significant (being p=0.000, p=0.009, and p=0.036 respectively). Conclusion: The determinants of success at the UTME of the JAMB among others are associated with students’ quality of input in preparing for the examinations. There are roles to be played at multiple levels to achieve needed improvement.&nbsp

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

A eukaryote assemblage intercalated with Marinoan glacial deposits in South Australia

Video of digital X-ray tomographs (µCT) in longitudinal plane through cylinder of siltstone, maximum diameter seen (left to right when viewing movie) is 5.4m

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define