Using law to identify, manage and prevent child maltreatment

This chapter identifies ways in which laws are capable of responding to child maltreatment, both as an immediate regulator of conduct, and as an influence on a society’s cultural development and approach to children’s welfare. Informed by practices and experiences in selected common law systems, the chapter provides examples of legal mechanisms that can inform discussion of optimal strategies to identify and manage child maltreatment in many different societies. Both positive and negative aspects of these mechanisms are noted. While controversies arise as to what kinds of laws are best in preventing and responding to child maltreatment, and even, more fundamentally, whether there is a role for law in protecting children, this chapter offers evidence that a variety of legal tools can be employed to address child abuse and neglect, for any cultural setting in which there is willingness to act to prevent and treat its various forms.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Hoffman Family collection.

Offprint on the "Jews in Altenmuhr" by Wielfried Jung. Manuscript commissioned by Richard Hoffman "A History of the Hoffman Family in Germany and the United States (1988). Pictures of Kleinbardorf and Massbach. Biographical material on Benjamin Hoffman. Democratic Party leaflet for Rebecca Hoffman. Report on family of David Louis Hoffman. Notes on the Heinemann branch. Manuscript by Douglas Hoffman "A History of Economic and Social Change in the Hoffman Family."

Investigation of the interaction between non-small cell lung cancer cells and immortalised normal bronchial epithelial cells

Non-small cell lung cancer consists of a diverse range of molecular and pathological features. This may be due in part to the critical interaction between normal and lung cancer cells. Consequently resulting in ‘normal’ cells acting in a malignant fashion. This project aims to identify pathways responsible for this altered ‘normal’ behaviour.

Examination of EXOSC4 as a new prognostic marker and a novel therapeutic avenue in lung adenocarcinoma

Although prevention and early detection of the disease greatly improved over the past few years, lung cancer remains the leading cause of cancer deaths. In order to be able to treat a larger population, we are in urgent need for novel treatments. While it is known that DNA repair genes play a major role in the oncogenic transformation, they also represent a weakness of cancers that constitute a therapeutic opportunity. To identify novel DNA repair genes implicated in Lung cancers, we conducted an in silico investigation to identify genes co-regulated with two DNA repair factors, BRCA2 and hSSB1. This approach allowed for the identification of EXOSC4, a component of the RNA Exosome machinery, as a potential factor involved in the maintenance of genome stability and that is deregulated in lung cancer.

CDCA3 regulates the cell cycle and modulates cisplatin sensitivity in non-small cell lung cancer

Cisplatin-based regimens are currently the most effective chemotherapy for non-small cell lung cancer (NSCLC). Cisplatin forms DNA crosslinks to stall DNA replication and induce apoptosis. However, intrinsic and acquired chemoresistance is a major therapeutic problem. We have identified ‘cell division cycle associated protein 3’ (CDCA3) as a novel protein that may prove useful in delaying or preventing cisplatin resistance in NSCLC. CDCA3 functions as part of an ubiquitin ligase complex to degrade the endogenous cell cycle inhibitors. While a role for CDCA3 in disease is emerging with elevated expression noted in oral squamous cell carcinoma, little else is known about CDCA3 or whether this protein may prove useful clinically.

Inflammatory meditated mechanisms of cisplatin resistance in non-small cell lung cancer

The majority of non-small cell lung cancer (NSCLC) patients present with advanced stage disease, where chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with cisplatin-based chemotherapy will eventually develop resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project is to determine the role of inflammatory mediators in cisplatin resistance.

The overexpression of SASH1 stimulates cell death in lung cancer cells

SASH1 (SAM and SH3 domain-containing protein 1) is a recently identified gene with tumour suppressor properties with a role in the induction of apoptosis. Previous work has shown that 90% of lung cell lines have a decrease in SASH1 mRNA levels, however little characterisation of SASH1 function in lung cancer has been undertaken.

Two Novel Hexadepsipeptides with Several Modified Amino Acid Residues Isolated from the Fungus

Two new cyclohexadepsipeptides have been isolated from the fungus Isaria. Fungal growth in solid media yielded hyphal strands from which peptide fractions were readily isolable by organic-solvent extraction. Two novel cyclodepsipeptides, isaridin A and isaridin B, have been isolated by reverse-phase HPLC, and characterized by ESI-MS and 1H-NMR. Single crystals of both peptides have been obtained, and their 3D structures were elucidated by X-ray diffraction. The isaridins contain several unusual amino acid residues. The sequences are cyclo(β-Gly-HyLeu-Pro-Phe-NMeVal-NMePhe) and cyclo(β-Gly-HyLeu-β-MePro-Phe-NMeVal-NMePhe), where NMeVal is N-methylvaline, NMePhe N-methylphenylalanine, and HyLeu hydroxyleucine (=2-hydroxy-4-methylpentanoic acid). The two peptides differ from one another at residue 3, isaridin A having an (S)-proline at this position, while β-methyl-(S)-proline (=(2S,3S)-2,3,4,5-tetrahydro-3-methyl-1H-pyrrole-2-carboxylic acid) is found in isaridin B. The solid-state conformations of both cyclic depsipeptides are characterized by the presence of two cis peptide bonds at HyLeu(2)-Pro(3)/HyLeu(2)-β-MePro(3) and NMeVal(5)-NMePhe(6), respectively. In isaridin A, a strong intramolecular H-bond is observed between Phe(4)CO⋅⋅⋅HNβ-Gly(1), and a similar, but weaker, interaction is observed between β-Gly(1)CO⋅⋅⋅HNPhe(4). In contrast, in isaridin B, only a single intramolecular H-bond is observed between β-Gly(1)CO⋅⋅⋅HNPhe(4

Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N-6-adenine DNA methyltransferases of Neisseria meningitidis

Phase variation (random ON/OFF switching) of gene expression is a common feature of host-adapted pathogenic bacteria. Phase variably expressed N-6-adenine DNA methyltransferases (Mod) alter global methylation patterns resulting in changes in gene expression. These systems constitute phase variable regulons called phasevarions. Neisseria meningitidis phasevarions regulate genes including virulence factors and vaccine candidates, and alter phenotypes including antibiotic resistance. The target site recognized by these Type III N-6-adenine DNA methyltransferases is not known. Single molecule, real-time (SMRT) methylome analysis was used to identify the recognition site for three key N. meningitidis methyltransferases: ModA11 (exemplified by M.NmeMC58I) (5'-CGY(m6)AG-3'), ModA12 (exemplified by M.Nme77I, M.Nme18I and M.Nme579II) (5'-AC(m6)ACC-3') and ModD1 (exemplified by M.Nme579I) (5'-CC(m6)AGC-3'). Restriction inhibition assays and mutagenesis confirmed the SMRT methylome analysis. The ModA11 site is complex and atypical and is dependent on the type of pyrimidine at the central position, in combination with the bases flanking the core recognition sequence 5'-CGY(m6)AG-3'. The observed efficiency of methylation in the modA11 strain (MC58) genome ranged from 4.6% at 5'-GCGC(m6)AGG-3' sites, to 100% at 5'-ACGT(m6)AGG-3' sites. Analysis of the distribution of modified sites in the respective genomes shows many cases of association with intergenic regions of genes with altered expression due to phasevarion switching.

Ecology of Juvenile Walleye Pollock, Theragra chalcogramma: Papers from the workshop "The Importance of Prerecruit Walleye Pollock to the Bering Sea and North Pacific Ecosystems" Seattle, Washington, 28-30 October 1993

The Alaska Fisheries Science Center (AFSC), National Marine Fisheries Service (NMFS), hosted an international workshop, 'The Importance of Prerecruit Walleye Pollock to the Bering Sea and North Pacific Ecosystems," from 28 to 30 October 1993. This workshop was held in conjunction with the annual International North Pacific Marine Science Organization (PICES) meeting held in Seattle. Nearly 100 representatives from government agencies, universities, and the fishing industry in Canada, Japan, the People's Republic of China, Russia, and the United States took part in the workshop to review and discuss current knowledge on juvenile pollock from the postlarval period to the time they recruit to the fisheries. In addition to its importance to humans as a major commercial species, pollock also serves as a major forage species for many marine fishes, birds, and mammals in the North Pacific region. (PDF file contains 236 pages.)

Food habits and dietary variability of pelagic nekton off Oregon and Washington, 1979-1984

The food habits of 20 species of pelagic nekton were investigated from collections made with small-mesh purse seines from 1979-84 off Washington and Oregon. Four species (spiny dogfish, Squalus acanthias; soupfin shark, Galeorhinus zyopterus; blue shark, Prionace glauca; and cutthroat trout, Salmo clarki) were mainly piscivorous. Six species (coho salmon, Oncorhynchus kisutch; chinook salmon, O. tshawytscha; black rockfish, Sebastes melanops; yellowtail rockfish, S. f1avidus; sablefish, Anoplopoma fimbria; and jack mackerel, Trachurus symmetricus) consumed both nektonic and planktonic organisms. The remaining species (market squid, Loligo opalescens; American shad, Alosa sapidissima; Pacific herring, Clupea harengus pallasi; northern anchovy, Engraulis mordax; pink salmon, O. gorbuscha; surf smelt, Hypomesus pretiosus; Pacific hake, Merluccius productus; Pacific saury, Cololabis saira; Pacific mackerel, Scomber japonicus; and medusafish, Icichthys lockingtom) were primarily planktonic feeders. There were substantial interannual, seasonal, and geographic variations in the diets of several species due primarily to changes in prey availability. Juvenile salmonids were not commonly consumed by this assemblage of fishes (PDF file contains 36 pages.)

Distribution and relative abundance of pelagic nonsalmonid nekton Off Oregon and Washington, 1979-84

Fifteen fine-mesh (32-mm mesh) pelagic purse seine surveys were conducted between 1979 and 1984 off the Oregon and Washington coasts. Environmental conditions varied greatly among the years sampled, and even within years, due to variability in upwelling conditions and productivity and the effects of a strong El Nino from late 1982 to the middle of 1984. In the 843 sets made, a total of 115,891 specimens from 69 taxa was collected. Most individuals collected belonged to nine dominant taxa. Seasonal and interannual variations in the abundance and distribution patterns of these dominant taxa are presented in detail. A recurrent group analysis delineated four major groupings of nekton. (PDF file contains 91 pages.)

Using experiments and expert judgment to model catchability of Pacific rockfishes in trawl surveys, with application to bocaccio (Sebastes paucispinis) off British Columbia

The time series of abundance indices for many groundfish populations, as determined from trawl surveys, are often imprecise and short, causing stock assessment estimates of abundance to be imprecise. To improve precision, prior probability distributions (priors) have been developed for parameters in stock assessment models by using meta-analysis, expert judgment on catchability, and empirically based modeling. This article presents a synthetic approach for formulating priors for rockfish trawl survey catchability (qgross). A multivariate prior for qgross for different surveys is formulated by using 1) a correction factor for bias in estimating fish density between trawlable and untrawlable areas, 2) expert judgment on trawl net catchability, 3) observations from trawl survey experiments, and 4) data on the fraction of population biomass in each of the areas surveyed. The method is illustrated by using bocaccio (Sebastes paucipinis) in British Columbia. Results indicate that expert judgment can be updated markedly by observing the catch-rate ratio from different trawl gears in the same areas. The marginal priors for qgross are consistent with empirical estimates obtained by fitting a stock assessment model to the survey data under a noninformative prior for qgross. Despite high prior uncertainty (prior coefficients of variation ≥0.8) and high prior correlation between qgross, the prior for qgross still enhances the precision of key stock assessment quantities.