Defects in the IFT-B Component IFT172 Cause Jeune and Mainzer-Saldino Syndromes in Humans.

Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A

Artificial intelligence (AI): multidisciplinary perspectives on emerging challenges, opportunities, and agenda for research and practice

As far back as the industrial revolution, great leaps in technical innovation succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision making engendering new opportunities for continued innovation. The impact of AI is significant, with industries ranging from: finance, retail, healthcare, manufacturing, supply chain and logistics all set to be disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: technological, business and management, science and technology, government and public sector. The research offers significant and timely insight to AI technology and its impact on the future of industry and society in general

Drug-sensitive ecto-ATPase in human leukocytes

An ecto-ATPase has been described in human leukocytes. The enzyme is present in both granulocytes and lymphocytes, exhibiting higher activity and substrate affinity in the latter cells, Km values ranged from 0.06 mM in lymphocytes to 0.3 mM in the unresolved leukocyte fraction. Enzymatic activity had a pH optimum in the physiological range, required Mg2+, and was insensitive toward ouabain and Ca2+. Potent inhibitors of ecto-ATPase were tricyclic antidepressants and substituted phenothiazines, to which the enzyme in lymphocytes was most susceptible. These drugs also decreased the phagocytic ability of leukocytes. However, while drug inhibition of the enzyme was reversible by washing, the effect on phagocytosis was not.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23163/1/0000088.pd

Immunohistochemical Localization of Prolactin Receptors Within the Equine Ovary

© 2015 Elsevier Inc. Prolactin (PRL) is hypothesized to stimulate follicular growth through a physiological action at the ovary. Immunohistochemistry was used to identify PRL receptors (PRLrs) within the equine ovary. Prolactin receptors were detected in anestrous (n = 3), winter cycling (n = 2), summer follicular (n = 3), and luteal phase (n = 3) ovaries. Prolactin receptors were detected in follicles of all stages, in corpus luteum and on oocytes. Staining intensity did not differ (P \u3e .05) between primordial and preantral follicles but was greater (P \u3c .001) in antral follicles than in primordial or preantral follicles. Greater PRLr staining (P \u3c .001) occurred in winter cycling primordial follicles (1.58 ± 0.09) than anestrous (0.67 ± 0.10) and summer luteal phase primordial follicles (1.16 ± 0.12; P \u3c .01) but not in primordial follicles during the summer follicular phase (P \u3e .05). Prolactin receptor staining in preantral follicles during anestrus was lower (P \u3c .05) than for all other reproductive states. Winter cycling and summer luteal phase preantral follicles stained most intensely, and both had greater PRLr staining than preantral follicles from anestrous ovaries (P \u3c .001) or summer follicular phase ovaries (P \u3c .001). Prolactin receptor staining of antral follicles was the most intense of all follicular sizes and did not vary (P \u3e .10) between reproductive states. Prolactin receptor staining was also detected in luteal tissue. In conclusion, PRLrs were detected in all stages of follicular growth with staining intensity highest in large antral follicles, indicating a possible mechanistic role for PRL during late stage follicular growth and perhaps ovulation