A developmental analysis of communication between mothers and infants with Down's syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68850/2/10.1177_027112148300300110.pd

A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression

Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma. PD-L1 is a co-inhibitory molecule whose expression on the surface of tumor cells is associated with worse prognosis in many tumors. Here we describe a splice variant (secPD-L1) that does not splice into the transmembrane domain, but instead produces a secreted form of PD-L1 that has a unique 18 amino acid tail containing a cysteine that allows it to homodimerize and more effectively inhibit lymphocyte function than monomeric soluble PD-L1. We show that recombinant secPD-L1 can dimerize and inhibit T-cell proliferation and IFN-gamma production in vitro. The secPD-L1 variant is expressed by malignant cells in vitro that also express high levels of full-length PD-L1. Transcriptomic analysis of gene expression across The Cancer Genome Atlas found the strongest association of secPD-L1 with full-length PD-L1, but also with subsets of immunologic genes, such as in myeloid-derived suppressor cells. Moreover, the splice variant is also expressed in normal tissues and within normal peripheral blood cells it is preferentially expressed in activated myeloid cells. This is the first report of a form of secreted PD-L1 that homodimerizes and is functionally active. SecPD-L1 may function as a paracrine negative immune regulator within the tumor, since secPD-L1 does not require a cell-to-cell interaction to mediate its inhibitory effect

Understanding morphological variation in the extant koala as a framework for identification of species boundaries in extinct koalas (Phascolarctidae; Marsupialia)

We document morphological variation (both geographical and sexual) in the dentition of the extant koala, Phascolarctos cinereus, in order to facilitate discrimination of species boundaries in extinct phascolarctids. Considerable variation is evident in dental structures previously used to diagnose several phascolarctid fossil species. Consistent patterns of morphological variation are not evident between sexes or geographic regions, with variation as great between samples as within them. Metric variation is evident between the sexes in upper molar dimensions with Victorian (southern) males significantly larger than Victorian females, although this is not reflected in lower molar dimensions or in the Queensland (northern) sample. Male koalas from southern populations generally display significantly larger molars than their northern counterparts; however this trend is not evident in female upper molar dimensions. In both males and females, some, but not all, lower molar dimensions are larger in southern populations than northern. In light of these results, a systematic revision of species of Litokoala suggests L. dicktedfordi' is a junior synonym of L. kutjamarpensis, and the poorly known L. thurmerae is regarded to be a nomen dubium. Further, we describe a partial cranium of a new species of koala from Early Miocene sediments in the Riversleigh World Heritage Area, northern Australia. Litokoala dicksmithi sp. nov. is the fifth koala species recorded from the diverse rainforest assemblages of Riversleigh and the third species referred to the Oligo-Miocene genus Litokoala. Aspects of cranial morphology, including a shortened robust rostrum and broad, irregular nasal aperture, confirm placement of Litokoala as sister taxon to the modern genus Phascolarctos. Relatively large orbits and small body size suggest the possibility that L. dicksmithi was nocturnal, had enhanced visual acuity, and was a more agile arboreal species than the relatively sedentary extant koala

The Role of Radioactivities in Astrophysics

I present both a history of radioactivity in astrophysics and an introduction to the major applications of radioactive abundances to astronomy

Transmissão transovariana de Babesia bovis em Boophilus microplus: obtenção de cepa de carrapato livre de Babesia spp. Babesia bovis transovarian transmission in Boophilus microplus: obtention of a Babesia free tick strain

O presente trabalho objetivou o estudo de parte do ciclo da Babesia bovis no seu hospedeiro invertebrado, o carrapato Boophilus microplus. Analisou-se a capacidade de infeccção e transmissão transovariana de B. bovis em partenóginas de B. microplus, alimentadas em bovinos portadores e enfermos por esse protozoário. No 18º dia após a infestação, coletaram-se partenóginas diretamente do corpo dos bovinos e teleóginas após o desprendimento natural, a partir do 21º dia. Todos os grupos foram incubados a 27ºC e umidade relativa superior a 70%. No 5º dia após o início da postura, realizou-se o exame de hemolinfa a fim de diagnosticar a infecção dos ínstares por B. bovis. A ausência de infecção detectada no exame de hemolinfa foi confirmada posteriormente com o teste biológico, revelando que partenóginas não transmitem B. bovis transovarianamente. Esses resultados oferecem uma técnica simplificada para a obtenção de cepas de carrapatos livres de B. bovis.<br>In this experiment part of the life cycle of Babesia bovis in its invertebrate host, the tick Boophilus microplus was studied. In order to evaluate the capacity of infection and transmission of B. bovis were collected semi-engorged females of B. microplus fed on carrier and ill bovines. In the 18th day after infestation, semi-engorged females were collected directly from bovine bodies and after 21st day engorged females dropped on the ground. All the collected groups were incubated at 27°C and relative humidity greater than 70%. At the 5th day of oviposition the diagnosis was made by direct examination of haemolymph smears. The biological test reveled that B. bovis transovarial transmission doesn't happer in semi-engorged females. The results offer a simple techique to obtain strains of ticks free of B. bovis