Action of manganese on puberty

Manganese (Mn) is considered important for normal growth and reproduction. Because Mn can cross the blood brain barrier and accumulate in the hypothalamus, and because it has been suggested that infants and children are potentially more sensitive to Mn than adults, we wanted to determine the effects of Mn exposure on puberty-related hormones and the onset of puberty, and discern the site and mechanism of Mn action. We demonstrated that the central administration of manganese chloride (MnCl2) stimulated luteinizing hormone (LH) release in prepubertal rats. Incubation of medial basal hypothalamus (MBH) in vitro showed this effect was due to a Mn-induced stimulation of luteinizing hormone releasing hormone (LHRH). Further demonstration that this is a hypothalamic site of action was shown by in vivo blockade of LHRH receptors and the lack of a direct pituitary action of Mn to stimulate LH release in vitro. Chronic supplementation of low dose of MnCl2 caused elevated serum levels of LH, follicle stimulating hormone (FSH) and estradiol or testosterone. Importantly, Mn supplementation advanced the timing of puberty in both sexes. We investigated the mechanism by which Mn induces LHRH/LH release from the hypothalamus. Blocking the NMDA receptor, IGF1 receptor, or inhibiting nitric oxide synthase in vivo was ineffective in altering Mn-induced LH release. Dose-response, pharmacological blockade and nitrite assessments indicated that the lowest doses of Mn used stimulated LHRH release, but did not induce nitric oxide (NO) production, while only the highest dose of Mn stimulated NO. Conversely, a dose-dependent inhibition of Mn-induced LHRH release was observed in the presence of ODQ, a specific blocker of soluble guanylyl cyclase. Furthermore, Mn stimulated the release of cyclic GMP (cGMP) and LHRH from the same MBH, and a protein kinase G (PKG) inhibitor, KT5823, blocked Mn-induced LHRH release. Collectively, these data demonstrate that Mn can stimulate specific puberty-related hormones both acutely and chronically, and furthermore, suggest that low levels of Mn facilitate the normal onset of puberty. The principal action of Mn within the hypothalamus is to facilitate the activation of guanylyl cyclase, which subsequently stimulates the cGMP/PKG pathway resulting in the stimulation of prepubertal LHRH secretion

A Statistical Verification Method of Random Permutations for Hiding Countermeasure Against Side-Channel Attacks

As NIST is putting the final touches on the standardization of PQC (Post Quantum Cryptography) public key algorithms, it is a racing certainty that peskier cryptographic attacks undeterred by those new PQC algorithms will surface. Such a trend in turn will prompt more follow-up studies of attacks and countermeasures. As things stand, from the attackers' perspective, one viable form of attack that can be implemented thereupon is the so-called "side-channel attack". Two best-known countermeasures heralded to be durable against side-channel attacks are: "masking" and "hiding". In that dichotomous picture, of particular note are successful single-trace attacks on some of the NIST's PQC then-candidates, which worked to the detriment of the former: "masking". In this paper, we cast an eye over the latter: "hiding". Hiding proves to be durable against both side-channel attacks and another equally robust type of attacks called "fault injection attacks", and hence is deemed an auspicious countermeasure to be implemented. Mathematically, the hiding method is fundamentally based on random permutations. There has been a cornucopia of studies on generating random permutations. However, those are not tied to implementation of the hiding method. In this paper, we propose a reliable and efficient verification of permutation implementation, through employing Fisher-Yates' shuffling method. We introduce the concept of an n-th order permutation and explain how it can be used to verify that our implementation is more efficient than its previous-gen counterparts for hiding countermeasures.Comment: 29 pages, 6 figure

Novel Single-Trace ML Profiling Attacks on NIST 3 Round candidate Dilithium

Dilithium is a lattice-based digital signature, one of the finalist candidates in the NIST\u27s standardization process for post-quantum cryptography. In this paper, we propose a first side-channel attack on the process of signature generation of Dilithium. During the Dilithium signature generation process, we used NTT encryption single-trace for machine learning-based profiling attacks. In addition, it is possible to attack masked Dilithium using sparse multiplication. The proposed method is shown through experiments that all key values can be exposed 100% through a single-trace regardless of the optimization level