Heterozygosity and ethnic variation in Japanese platelet proteins

Sixty-two polypeptides visualized on silver-stained two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) preparations of platelets from 85 Japanese subjects, in total 5,252 spots, have been scored for genetic variation. Inherited variants of 11 of the polypeptides were recognized; the index of heterozygosity was 2.4%±0.2%. Thus far, 10 genetic polymorphisms identified by 2-D PAGE of plasma, erythrocytes, or platelets have been identified in both Japanese and Caucasian subjects. A comparison of allele frequencies reveals four significant ethnic differences. We also observed four polypeptides exhibiting a low frequency polymorphism in one group but not in the other, as well as three polymorphisms in Caucasians for which no counterpart polypeptide has thus far been recognized in the Japanese group and, vice versa, 11 such polymorphisms in Japanese. Although a similar comparison of 7 enzyme polymorphisms studied with one-dimensional electrophoresis (1-D E) in the same populations revealed a relatively higher number of significant ethnic differences, evidence is presented that this is due primarily to the greater number of 1-D E observations entering into the calculation. It is argued that this similarity in the frequency of ethnic differences among the polypeptides studied by 2-D PAGE and by 1-D E is further evidence that the proteins revealed by 2-D PAGE do not differ greatly in their response to the interplay of mutation, selection, and drift from those revealed by 1-D E studies of plasma proteins and erythrocyte enzymes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47621/1/439_2004_Article_BF00291224.pd

In Defence of Political Parties: A Symposium on Jonathan White and Lea Ypi’s The Meaning of Partisanship

A symposium on Jonathan White and Lea Ypi's The Meaning of Partisanship (Oxford University Press, 2016), with replies from the authors

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

Development of a new marker system for identifying the complex members of the low-molecular-weight glutenin subunit gene family in bread wheat (Triticum aestivum L.)

Low-molecular-weight glutenin subunits (LMW-GSs) play an important role in determining the bread-making quality of bread wheat. However, LMW-GSs display high polymorphic protein complexes encoded by multiple genes, and elucidating the complex LMW-GS gene family in bread wheat remains challenging. In the present study, using conventional polymerase chain reaction (PCR) with conserved primers and high-resolution capillary electrophoresis, we developed a new molecular marker system for identifying LMW-GS gene family members. Based on sequence alignment of 13 LMW-GS genes previously identified in the Chinese bread wheat variety Xiaoyan 54 and other genes available in GenBank, PCR primers were developed and assigned to conserved sequences spanning the length polymorphism regions of LMW-GS genes. After PCR amplification, 17 DNA fragments in Xiaoyan 54 were detected using capillary electrophoresis. In total, 13 fragments were identical to previously identified LMW-GS genes, and the other 4 were derived from unique LMW-GS genes by sequencing. This marker system was also used to identify LMW-GS genes in Chinese Spring and its group 1 nulli–tetrasomic lines. Among the 17 detected DNA fragments, 4 were located on chromosome 1A, 5 on 1B, and 8 on 1D. The results suggest that this marker system is useful for large-scale identification of LMW-GS genes in bread wheat varieties, and for the selection of desirable LMW-GS genes to improve the bread-making quality in wheat molecular breeding programmes

Neonatal Handling Affects Durably Bonding and Social Development

The neonatal period in humans and in most mammals is characterized by intense mother-young interactions favoring pair bonding and the adaptation of neonates to their new environment. However, in many post-delivery procedures, human babies commonly experience combined maternal separation and intense handling for about one hour post-birth. Currently, the effects of such disturbances on later attachment and on the development of newborns are still debated: clearly, further investigations are required. As animals present good models for controlled experimentation, we chose domestic horses to investigate this issue. Horses, like humans, are characterized by single births, long lactating periods and selective mother-infant bonds. Routine postnatal procedures for foals, as for human babies, also involve intense handling and maternal separation. In the present study, we monitored the behavior of foals from early stages of development to “adolescence”, in a normal ecological context (social groups with adults and peers). Experimental foals, separated from their mothers and handled for only 1 hour post-birth, were compared to control foals, left undisturbed after birth. Our results revealed short- and long-term effects of this unique neonatal experience on attachment and subsequent social competences. Thus, experimental foals presented patterns of insecure attachment to their mothers (strong dependence on their mothers, little play) and impaired social competences (social withdrawal, aggressiveness) at all ages. We discuss these results in terms of mother-young interactions, timing of interactions and relationships between bonding and subsequent social competences. Our results indicate that this ungulate species could become an interesting animal model. To our knowledge, this is the first clear demonstration that intervention just after birth affects bonding and subsequent social competences (at least until “adolescence”). It opens new research directions for studies on both humans and other animals

The Anatomy of Neighbour Relations

Relations between neighbours represent informal social relations that constitute a part of everyday life for virtually all individuals in contemporary urban societies. While aspects of neighbour relations have been studied in connection with research on local communities, gentrification, and neighbourhood effects, little research focusing specifically on interactions between neighbours has been conducted and theoretical reflection on the central concepts remains lacking. This article attempts to fill this research gap by developing a theoretical framework for the sociological understanding and investigation of neighbour relations. The research material used consists of previous studies on neighbour relations. The method for the task was analysis of concepts coupled with theoretical reasoning based on a review and a synthesis of relevant previous research. Familiar concepts like ‘neighbour’, ‘neighbouring’, and ‘neighbourliness’ are scrutinised, deconstructed, and redefined, noting that there are often two perspectives on each: the experiences of residents and those of outside observers. Various sociological aspects of neighbour relations are discussed, including neighbour relations as an acquaintance relation, neighbour relations as the basis of a community, and the cultural content of the neighbour role. A model of levels of neighbourly interaction is presented