Conservation and management measures for large mobile sharks are more effective when information on migratory patterns and environmental cues are known. In the absence of long-term monitoring data or ...tracking programs, available information is based on occasional catch or sighting records from a variety of sources, usually constrained in space and time. This study demonstrates the utility of developing temporally explicit habitat suitability (HS) models to infer the migratory pattern of large mobile sharks. Bimonthly presence-only HS models (MaxEnt algorithm) were developed for the broadnose sevengill shark (Notorynchus cepedianus) in the southwest Atlantic based on an exhaustive collection of data records and ecologically relevant predictors. The six final models showed good predictive power and were evaluated with independent data. A migratory pattern characterized by two main displacements was inferred from the models. We show that HS models can be applied as a no-cost, desk-based alternative to infer broadscale movements of large mobile sharks. This methodology is relevant as an important first step toward informing management plans in data-poor and financially limited regions or regions under urgent conservation need.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Population-scale information on the spatial ecology of threatened mobile sharks is required to design more effective management measures. Using an exhaustive collection of presence-only records and ...relevant predictors, we applied temporally explicit environmental niche modelling to study habitat use by a school shark
Galeorhinus galeus
population in the Southwest Atlantic. As a complementary tool, we developed randomized habitat association curves to assess both the representation of data with biological information and possible intra-population variation in habitat use. Seasonal niche models supported a core area of distribution between southern Brazil and southern Argentina. Marginal seasonal variation in suitability at the northern and southern extremes of its distribution supported the hypothesis that the
G. galeus
population behaves to some degree as a niche shifter on an annual cycle. Habitat associations revealed regional bias in the collection of records with biological information, and suggested a complex intra-population segregation pattern between sexes and between maturity stages during the cold half of the year. Overall, results supported large-scale partial migrations (i.e. some individuals migrate while others remain resident) of the
G. galeus
population. This study demonstrates the significance of future regional efforts that focus on producing more and better databases to derive relevant information at a low cost for the management of threatened sharks and their relatives.
Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four ...independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.
Background. People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been ...associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. Methods. We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo, beta carotene (25 mg daily), vitamin C (1 g daily) and vitamin E (400 mg daily), or beta carotene plus vitamins C and E. In order to identity new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. Results. Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. Conclusions. The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.
One of the core courses in the undergraduate mechanical engineering curriculum has been completely redesigned. In the new numerical methods course, all assignments and learning experiences are built ...around a video/computer game. Students are given the task of writing computer programs to race a simulated car around a track. In doing so, students learn and implement numerical methods content. The design of the course, around a video game, is rooted in commonly accepted theories of how people learn. The article describes a study to assess the effectiveness of the video game-based course. Results show that students taking the game-based course, on average, spend roughly twice as much time, outside of class, on their course work. In a concept mapping exercise, students taking the game-based course demonstrate deeper learning compared to their counterparts taking traditional lecture/textbook-based numerical methods courses.
Abstract
The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial ...proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability.
We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster.
We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus.
In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment.
We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.
Fevga, Tesson, Carreras Mascaro, Courtin et al. identify homozygous PTPA variants co-segregating with parkinsonism and intellectual disability in two families. Both variants are associated with reduced PTPA levels and impaired activation of PP2A in vitro. PTPA knockdown in Drosophila induces levodopa-sensitive motor impairment.
Cellular quiescence, defined as reversible growth/proliferation arrest, is thought to represent a homogenous state induced by diverse anti-mitogenic signals. We used transcriptional profiling to ...characterize human diploid fibroblasts that exited the cell cycle after exposure to three independent signals--mitogen withdrawal, contact inhibition, and loss of adhesion. We show here that each signal caused regulation of a unique set of genes known to be important for cessation of growth and division. Therefore, contrary to expectation, cells enter different quiescent states that are determined by the initiating signal. However, underlying this diversity we discovered a set of genes whose specific expression in non-dividing cells was signal-independent, and therefore representative of quiescence per se, rather than the signal that induced it. This fibroblast "quiescence program" contained genes that enforced the non-dividing state, and ensured the reversibility of the cell cycle arrest. We further demonstrate that one mechanism by which the reversibility of quiescence is insured is the suppression of terminal differentiation. Expression of the quiescence program was not simply a downstream consequence of exit from the cell cycle, because key parts, including those involved in suppressing differentiation, were not recapitulated during the cell cycle arrest caused by direct inhibition of cyclin-dependent kinases. These studies form a basis for understanding the normal biology of cellular quiescence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recognition sites for microRNAs (miRNAs) have been reported to be located in the 3' untranslated regions of transcripts. In a computational screen for highly conserved motifs within coding regions, ...we found an excess of sequences conserved at the nucleotide level within coding regions in the human genome, the highest scoring of which are enriched for miRNA target sequences. To validate our results, we experimentally demonstrated that the let-7 miRNA directly targets the miRNA-processing enzyme Dicer within its coding sequence, thus establishing a mechanism for a miRNA/Dicer autoregulatory negative feedback loop. We also found computational evidence to suggest that miRNA target sites in coding regions and 3' UTRs may differ in mechanism. This work demonstrates that miRNAs can directly target transcripts within their coding region in animals, and it suggests that a complete search for the regulatory targets of miRNAs should be expanded to include genes with recognition sites within their coding regions. As more genomes are sequenced, the methodological approach that we used for identifying motifs with high sequence conservation will be increasingly valuable for detecting functional sequence motifs within coding regions.
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