Human NAD-dependent isocitrate dehydrogenase existing as the α2βγ heterotetramer, catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory β and γ subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing αβ and αγ heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that αβ and αγ alone have considerable basal activity but the full activity of α2βγ requires the assembly and cooperative function of both heterodimers. α2βγ and αγ can be activated by citrate or/and ADP, whereas αβ cannot. The binding of citrate or/and ADP decreases the S0.5,isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate α2βγ and αγ at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on αβ. Furthermore, the allosteric activation of α2βγ is through the γ subunit not the β subunit. These results demonstrate that the γ subunit plays regulatory role to activate the holoenzyme, and the β subunit the structural role to facilitate the assembly of the holoenzyme.

Sites like Facebook and Google now serve as de facto data brokers, aggregating data on users for the purpose of implementing powerful advertising platforms. Historically, these services allowed advertisers to select which users see their ads via targeting attributes. Recently, most advertising platforms have begun allowing advertisers to target users directly by uploading the personal information of the users who they wish to advertise to (e.g., their names, email addresses, phone numbers, etc.); these services are often known as custom audiences. Custom audiences effectively represent powerful linking mechanisms, allowing advertisers to leverage any PII (e.g., from customer data, public records, etc.) to target users. In this paper, we focus on Facebook's custom audience implementation and demonstrate attacks that allow an adversary to exploit the interface to infer users' PII as well as to infer their activity. Specifically, we show how the adversary can infer users' full phone numbers knowing just their email address, determine whether a particular user visited a website, and de-anonymize all the visitors to a website by inferring their phone numbers en masse. These attacks can be conducted without any interaction with the victim(s), cannot be detected by the victim(s), and do not require the adversary to spend money or actually place an ad. We propose a simple and effective fix to the attacks based on reworking the way Facebook de-duplicates uploaded information. Facebook's security team acknowledged the vulnerability and has put into place a fix that is a variant of the fix we propose. Overall, our results indicate that advertising platforms need to carefully consider the privacy implications of their interfaces.

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The sharing of personal data has emerged as a popular activity over online social networking sites like Facebook. As a result, the issue of online social network privacy has received significant attention in both the research literature and the mainstream media. Our overarching goal is to improve defaults and provide better tools for managing privacy, but we are limited by the fact that the full extent of the privacy problem remains unknown; there is little quantification of the incidence of incorrect privacy settings or the difficulty users face when managing their privacy.In this paper, we focus on measuring the disparity between the desired and actual privacy settings, quantifying the magnitude of the problem of managing privacy. We deploy a survey, implemented as a Facebook application, to 200 Facebook users recruited via Amazon Mechanical Turk. We find that 36% of content remains shared with the default privacy settings. We also find that, overall, privacy settings match users' expectations only 37% of the time, and when incorrect, almost always expose content to more users than expected. Finally, we explore how our results have potential to assist users in selecting appropriate privacy settings by examining the user-created friend lists. We find that these have significant correlation with the social network, suggesting that information from the social network may be helpful in implementing new tools for managing privacy.

Mammalian mitochondrial NAD-dependent isocitrate dehydrogenase (NAD-IDH) catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the tricarboxylic acid cycle. It exists as the α2βγ heterotetramer composed of the αβ and αγ heterodimers. Different from the αγ heterodimer that can be allosterically activated by CIT and ADP, the αβ heterodimer cannot be allosterically regulated by the activators; however, the molecular mechanism is unclear. We report here the crystal structures of the αβ heterodimer of human NAD-IDH with the α subunit in apo form and in Ca2+-bound, NAD-bound, and NADH-bound forms. Structural analyses and comparisons reveal that the αβ heterodimer has a similar yet more compact overall structure compared with the αγ heterodimer and contains a pseudo-allosteric site that is structurally different from the allosteric site. In particular, the β3-α3 and β12-α8 loops of the β subunit at the pseudo-allosteric site adopt significantly different conformations from those of the γ subunit at the allosteric site and hence impede the binding of the activators, explaining why the αβ heterodimer cannot be allosterically regulated by the activators. The structural data also show that NADH can compete with NAD to bind to the active site and inhibits the activity of the αβ heterodimer. These findings together with the biochemical data reveal the molecular basis for the function of the αβ heterodimer of human NAD-IDH.