Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

Note on occurrence of Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) in Montana: a new state record

The parasitic wasp Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) was collected at 4 sites within a canyon reach of the Kootenai River in Lincoln County, Montana. This minute species has only recently been described, but it appears to have a large distribution throughout the United States and to be associated with upland and riparian forests. La avispa parasitaria Mymaromella pala Huber y Gibson (Hymenoptera: Mymarommatidae) se recolectó en cuatro sitios a lo largo de un cañón del Río Kootenai en Lincoln Co., MT. Hace poco que se describió esta especie diminuta, pero parece tener una distribución extensa en los EE.UU. y estar asociada con bosques altos y ribereños.     

Operationalising “Double-Loop” Learning in Service Organisations: A Systems Approach for Creating Knowledge

Learning organisation literature has widely discussed the connections between “double-loop” learning and its significance to organisational performance, but paying little attention to tools and systems that can operationalise “double-loop” learning in organisations. This paper investigates the impact of applying a systems approach for service operations design, expressed as the Vanguard Method (Seddon, Freedom from command and control: a better way to make the work work, 2003), in order to activate “double-loop” learning in service organisations. Two case studies were conducted in the banking mortgage operations and adults’ social care services in the UK, using the dimensions of the learning organisation questionnaire (DLOQ), semi-structured interviews, observations, and documents. The findings of the cross-case analysis support the link of applying the Vanguard Method with operationalising “double-loop” learning through three main factors, namely systematic-operations improvement, organisational capacity development, and outside-in mode of work; that are all embedded into the seven dimensions of the DLOQ. The value of this paper is the introduction of a service operations design tool that can activate “double-loop” learning performance in the fast changing knowledge era. It also provides an impetus for service organisations to creatively influence employees’ competencies to effectively improve internal systems.     

2004-based national population projections for the UK and constituent countries

The 2004-based national population projections, carried out by the Government Actuary in consultation with the Registrars General, show the population of the United Kingdom (UK) rising from 59.8 million in 2004, passing 60 million in 2005 and 65 million in 2023, to reach 67.0 million by 2031. In the longer-term, the projections suggest that the population will continue rising beyond 2031 but at a much lower rate of growth. The population will become older with the median age expected to rise from 38.6 years in 2004 to 42.9 years by 2031. With the current plans for a common state pension age of 65 for both sexes from 2020, the number of people of working age for every person of state pensionable age is projected to fall from 3.33 in 2004 to 2.62 by 2031.     

Habitat use of leatherside chub ( Gila copei ) in the presence of predatory brown trout ( Salmo trutta )

The objectives of this study were to (1) examine distribution and habitat use of leatherside chub ( Gila copei ) in a creek with high densities of predatory brown trout ( Salmo trutta ), and (2) compare study results with published accounts of leatherside chub habitat use in streams with few or no brown trout. A 14-km section of Diamond Fork Creek, Utah, was point-shocked to determine macrohabitat (main channel and lateral habitat) and microhabitat (current, depth, substrate, and cover) use of leatherside chug. At the macrohabitat level, leatherside chub were most common in lower reaches of Diamond Fork Creek where the channel was braided and lateral habitats (cutoff pools and backwaters) were abundant. Only a single leatherside chub was found in the main channel of Diamond Fork. Investigations in other systems lacking brown trout indicated that leatherside chub occupy main channel habitats. At the microhabitat level, we found significant positive associations between presence of leatherside chub and both habitat depth and silt. In addition, we found a significant negative association between presence of leatherside chub and number of brown trout. Our results suggest predation by brown trout may limit leatherside chub to lateral habitats that could provide refugia against predation. The introduction of brown trout to systems with little lateral habitat could have serious effects on persistence of resident leatherside chub populations.     

Winter food habits of cougars from northeastern Oregon

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} Sixty-four cougar ( Felis concolor ) stomachs and 41 intestinal tracts were examined for food items in northeastern Oregon from 1976 through 1979. Food items, in order of decreasing frequency, were mule deer ( Odocoileus hemionus ), North American elk ( Cervus elaphus ), porcupine ( Erethizon dorsatum ), snowshoe hare ( Lepus americanus ), and deer mouse ( Peromyscus maniculatus ).       

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans (jawless fish) and of immunoglobulin gene segments in gnathostomes (jawed vertebrates).