APOB gene signal peptide deletion polymorphism is not associated with infertility in Indian men

Apolipoprotein B (APOB) plays a key role in lipoprotein metabolism and plasma lipid transport. It has been shown that about two-thirds of male mice heterozygous for ApoB were infertile. Moreover, a 3-codon deletion polymorphism (rs11279109) in the signal peptide region of the APOB gene has been shown to be a risk factor for infertility in Slovenian men, but its association with infertility in Indian men has not been evaluated to date. Hence, in the present study, we have genotyped this polymorphism in 545 Indian men, including 294 infertile and 251 fertile men. Our results show that the distribution of this deletion polymorphism was consistent with the Hardy-Weinberg equilibrium in both infertile and fertile men. No statistically significant difference was observed in the distribution of the APOB signal peptide deletion polymorphism between infertile and fertile men (χ2=0.156, P=.925 for genotypes; χ2=0.015, P=.903 for alleles). Moreover, no significant difference was observed when infertile and fertile men were categorized on the basis of presence (D/D and D/W genotypes) or absence (W/W genotypes) of deletion (odds ratio, 0.955; 95% confidence interval, 0.644-01.418; P=.820). Our study concludes that the APOB gene deletion polymorphism is not a risk factor for the development of infertility in Indian men

When a Patch is Not Enough - HardFails: Software-Exploitable Hardware Bugs

In this paper, we take a deep dive into microarchitectural security from a hardware designer's perspective by reviewing the existing approaches to detect hardware vulnerabilities during the design phase. We show that a protection gap currently exists in practice that leaves chip designs vulnerable to software-based attacks. In particular, existing verification approaches fail to detect specific classes of vulnerabilities, which we call HardFails: these bugs evade detection by current verification techniques while being exploitable from software. We demonstrate such vulnerabilities in real-world SoCs using RISC-V to showcase and analyze concrete instantiations of HardFails. Patching these hardware bugs may not always be possible and can potentially result in a product recall. We base our findings on two extensive case studies: the recent Hack@DAC 2018 hardware security competition, where 54 independent teams of researchers competed world-wide over a period of 12 weeks to catch inserted security bugs in SoC RTL designs, and an in-depth systematic evaluation of state-of-the-art verification approaches. Our findings indicate that even combinations of techniques will miss high-impact bugs due to the large number of modules with complex interdependencies and fundamental limitations of current detection approaches. We also craft a real-world software attack that exploits one of the RTL bugs from Hack@DAC that evaded detection and discuss novel approaches to mitigate the growing problem of cross-layer bugs at design time

Novel variants in UBE2B gene and idiopathic male infertility

The UBE2B gene encodes ubiquitin-conjugating enzyme, which is involved in DNA repair. Ube2b knockout mice were found to be infertile because of structural abnormality of sperm. However, there is no genetic study on the role of the UBE2B gene in human fertility; therefore, the present investigation was designed to study genetic variations in the UBE2B gene and its role in human male infertility. Sequence analyses of the UBE2B gene in 530 infertile (350 azoospermic, 105 oligoasthenoteratozoospermic, and 75 oligoasthenozoospermic) and 300 fertile control men revealed the presence of 5 substitution single-nucleotide polymorphisms (SNPs) in 221 individuals (199 infertile [37.5%] and 22 fertile [7.3%] men). Of these, 2 (g.5197:T>G; g.9157:A>G) of the 5 substitutions were novel and observed only in infertile men. Distribution of haplotypes TA, TG, GA, and GG are not uniform between the patient and the control group of this study. Interestingly, our study suggests that the haplotype TG conferred significantly increased risk for male infertility (odds ratio=5.07, 95% CI=1.29-23.29, p=.007). In silico analysis of SNPs that were specific to infertile men predicted that these SNPs lead to defective splicing by destroying or creating the potential binding site of splicing factors or causing alteration in predicted regulatory sequences. In the light of the above, our study suggests that the UBE2B gene is associated with male infertility in Indian men, hence, providing evidence for additional genetic factors for male infertility

Sialyltransferases and Neuraminidases: Potential Targets for Cancer Treatment

Cancers are the leading cause of death, causing around 10 million deaths annually by 2020. The most common cancers are those affecting the breast, lungs, colon, and rectum. However, it has been noted that cancer metastasis is more lethal than just cancer incidence and accounts for more than 90% of cancer deaths. Thus, early detection and prevention of cancer metastasis have the capability to save millions of lives. Finding novel biomarkers and targets for screening, determination of prognosis, targeted therapies, etc., are ways of doing so. In this review, we propose various sialyltransferases and neuraminidases as potential therapeutic targets for the treatment of the most common cancers, along with a few rare ones, on the basis of existing experimental and in silico data. This compilation of available cancer studies aiming at sialyltransferases and neuraminidases will serve as a guide for scientists and researchers working on possible targets for various cancers and will also provide data about the existing drugs which inhibit the action of these enzymes

When a Patch is Not Enough - HardFails: Software-Exploitable Hardware Bugs

Modern computer systems are becoming faster, more efficient, and increasingly interconnected with each generation. Consequently, these platforms also grow more complex, with continuously new features introducing the possibility of new bugs. Hence, the semiconductor industry employs a combination of different verification techniques to ensure the security of System-on-Chip (SoC) designs during the development life cycle. However, a growing number of increasingly sophisticated attacks are starting to leverage cross-layer bugs by exploiting subtle interactions between hardware and software, as recently demonstrated through a series of real-world exploits with significant security impact that affected all major hardware vendors