This obviously results in a profound decrease of enzymatic GLA activity in plasma. Additionally, this effect seems to be irreversible. Once in contact with a neutral or basic pH environment D313Y remains inactive, even if transferred to optimal pH. The GLA substrate Gb3, also known as CD77, has been shown to act as a cell surface receptor in apoptotic signaling triggered not only by Shiga toxin and Shiga-like toxins, but also by Gb3/CD77 antibodies. If extracellular GLA activity is involved in inactivation of CD77 or its removal from the cellular surface, then a decrease of extracellular GLA activity could lead to an increased initiation of apoptosis. If so, the occurrence of abundant WML and the mild FD symptoms in D313Y carriers points to a higher susceptibility of neural tissues to this possible pathomechanism. From the clinical point of view, the most appropriate time to start evaluating and follow-up the neurological manifestations of D313Y carriers, or whether and when starting treatment with ERT, remains to be investigated and should be based on more clinical data. We, therefore, decided to perform a follow-up MRI within 6 months and started a symptomatic treatment of the neuropathic pain of the index patient with pregabaline. If the neuropathic pain does not respond to appropriate medication, ERT should be suggested, in particular with regard to the excellent ERT response on neuropathic pain in appropriate studies. In case of a significant increase of WML an effective anti-platelet agent such as clopidogrel should be considered as an appropriate therapeutic option. However, vaccinated women must still attend programs for early detection of CC since these vaccines only protect against certain virus types, and it is not yet known how long the immune protection against the target virus remains.In this study, we offer in vitro evidence for the physiologic function of an HIV-1 signature identified through computational analyses of acute and chronic envelope sequences undertaken by colleagues. They found histidine to be significantly enriched at the amino acid 12 position of transmitted founder envelopes in comparison to chronic envelopes, where this residue was more likely to mutate to an amino acid other than histidine. We have demonstrated that the presence of a histidine or similarly positively charged arginine at this position, in comparison to non-basic residues, is associated with higher envelope expression and virion incorporation levels, and may influence viral infectivity. Unfortunately, pathologists often disagree on sub-classification of renal neoplasms based on morphology alone, with discordance rates as high as 50% in the non-clear-cell histologies. This leads to reliance on immunohistochemistry, but immunohistochemistry and morphology are often at odds.