TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.     

ADAMTS17 mutation associated with primary lens luxation is widespread among breeds

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3-15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL.     

Teasing apart socially‐induced infertility in non‐reproductive female Damaraland mole‐rats,Fukomys damarensis (Rodentia: Bathyergidae)

The Damaraland mole‐rat is a subterranean mammal exhibiting extreme reproductive skew with a single reproductive female in each colony responsible for procreation. Non‐reproductive female colony members are physiologically suppressed while in the colony, exhibiting reduced concentrations of plasma luteinizing hormone (LH) and a decreased response of the pituitary, as measured by the release of bioactive LH, to an exogenous dose of gonadotrophin releasing hormone (GnRH). Removal of the reproductive female from the colony results in an elevation of LH and an enhanced response of the pituitary to a GnRH challenge in non‐reproductive females comparable to reproductive females, implying control of reproduction in these individuals by the reproductive female. The Damaraland mole‐rat is an ideal model for investigating the physiological and behavioral mechanisms that regulate the hypothalamo–pituitary–gonadal axis. In contrast, we know less about the control of reproduction at the level of the hypothalamus. The immunohistochemistry of the GnRH system of both reproductive and non‐reproductive female Damaraland mole‐rats has revealed no significant differences with respect to morphology, distribution or numbers of immunoreactive GnRH perikarya. We examined whether the endogenous opioid peptide beta‐endorphin was responsible for the inhibition of the release of the GnRH from the neurons indirectly by measuring LH concentrations in these non‐reproductive females following single, hourly and 8 hourly injections of the opioid antagonist naloxone. The results imply that the endogenous opioid peptide, beta‐endorphin, is not responsible for the inhibition of GnRH release from the perikarya in non‐reproductive females. Preliminary data examining the circulating levels of cortisol also do not support a role for circulating glucocorticoids. The possible role of kisspeptin is discussed.     

Structural characteristics of a low Arctic tundra ecosystem and the retreat of the Arctic fox

We conducted a large-scale, campaign-based survey in Finnmark, northern Norway to evaluate the proposition that declining Arctic fox populations at the southern margin of the Arctic tundra biome result from fundamental changes in the state of the ecosystem due to climatic warming. We utilized the fact that the decline of the Arctic fox in Finnmark has been spatially heterogeneous by contrasting ecosystem state variables between regions and landscape areas (within regions) with and without recent Arctic fox breeding.Within the region of Varanger peninsula, which has the highest number of recorded dens and the most recent breeding records of Arctic fox, we found patterns largely consistent with a previously proposed climate-induced, bottom-up trophic cascade that may exclude the Arctic fox from tundra. Landscape areas surrounding dens without recent Arctic breeding were here more productive than areas with recent breeding in terms of biomass of palatable and climate sensitive plants, the number of insectivorous passerines and predatory skuas. Even the frequency of unspecified fox scats was the highest in landscape areas where arctic fox breeding has ceased, consistent with an invasion of the competitively dominant red fox. The comparisons made at the regional level were not consistent with the results within the Varanger region, possibly due to different causal factors or to deficiencies in Arctic fox monitoring at a large spatial scale. Thus long-term studies and adequate monitoring schemes with a large-scale design needs to be initiated to better elucidate the link between climate, food web dynamics and their relations to Arctic and red foxes.     

Orthopedic conditions that affect the avian pelvic limb.

Birds are often presented to the veterinarian with injury or disease that affects their ability to use one or both legs. Although in wild birds traumatic injuries usually involve the wing, captive birds especially falconer's birds, are usually presented with injuries to their legs. This article focuses on conditions affecting practice: birds of prey, and injured wild birds. The birds are presented with lameness or loss of use of the leg. The conditions described can be initiated by injury or by disease affecting an area other than the leg, such as the kidney or spinal cord, or they can be toxic or metabolic.     

Efficacy of tulathromycin in the treatment and prevention of natural outbreaks of bovine respiratory disease in European cattle

The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2) of bovine respiratory disease (BRD) was evaluated on commercial farms in France, Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar percentages of animals showed sustained clinical improvement at day 14 (tulathromycin 83.3% versus florfenicol 81.0%) and had not relapsed by day 60 (tulathromycin 63.3% versus florfenicol 58.4%). In phase 2, healthy in-contact cattle were treated with tulathromycin (n = 492), tilmicosin (n = 494), or saline (n = 265) on day 0. Significantly more (P = .0001) tulathromycin-treated cattle remained healthy to day 14 (92.4%) than tilmicosin-treated (83.7%) or saline-treated (63.7%) cattle, and this was maintained through day 60 (tulathromycin 85.4% versus tilmicosin 75.1% and saline 56.2%). Tulathromycin was highly effective in the treatment and prevention of BRD.     

Follicular and hormonal dynamics during the estrous cycle in goats

Transrectal ultrasonography of ovaries was performed daily in 6 goats for 3 consecutive estrous cycles. Blood samples collected daily were measured for concentrations of FSH, inhibin A, and estradiol-17beta. Follicular and hormonal data were analyzed for associations between the follicular waves and hormonal concentrations. During the interovulatory intervals, follicular growth and regression occurred in a wave like pattern (2-5 waves), and the predominant patterns were three and four follicular waves. In addition, there was no significant difference among the diameters of dominant follicles during the growth phase of the follicular waves. The number of 3 mm follicles peaked on days 0, 7, and 11 in interovulatory intervals that had three follicular waves and on days -1, 5, 11, and 15 in those that had four follicular waves. Plasma concentrations of FSH increased around the day of follicular wave emergence and declined with the growth of follicles. Circulating FSH increased again concomitant with regression of dominant follicles in the anovulatory wave, whereas FSH levels remained low in the ovulatory wave. Inhibin A was negatively correlated with FSH, while it was positively correlated with estradiol-17beta, suggesting that inhibin A is a product of healthy growing follicles and that it contributes to the suppression of FSH secretion. In conclusion, the growth of ovarian follicles in goats exhibits a wave-like pattern, and follicular dominance is less apparent in goats. Moreover, inhibin A may be a key hormone for regulation of the follicular wave through suppression of FSH secretion in goats.