Does the Mother or Father Determine the Offspring Sex Ratio? Investigating the Relationship between Maternal Digit Ratio and Offspring Sex Ratio

Objective

In mammals, high parental testosterone levels present around the time of conception are thought to skew offspring sex ratio toward sons. The second to fourth digit ratio (digit ratio) is now widely accepted as a negative correlate of prenatal testosterone. Thus, we investigated the association between digit ratio and offspring sex ratio.

Methods

A total of 508 Korean patients (257 males and 251 females) less than 60 years old who had one or more offspring were prospectively enrolled. The lengths of the 2nd and 4th digits of the right hand were measured by a single investigator using a digital vernier calliper. Next, the patients’ lifetime offspring birth sex ratios were investigated.

Results

Maternal (rather than paternal) digit ratio was significantly associated with the number of sons (r = -0.153, p = 0.015), number of daughters (r = 0.130, p = 0.039), and offspring sex ratio (r = -0.171, p = 0.007). And, the maternal digit ratio was a significant factor for predicting offspring sex ratio (B = -1.620, p = 0.008) on multiple linear regression analysis. The female patients with a lower digit ratio (< 0.95) were found to have a higher offspring sex ratio (0.609 versus 0.521, p = 0.046) compared to those with a higher digit ratio (≥ 0.95). Furthermore, females in the low digit ratio group have a probability 1.138 greater of having sons than females in the high digit ratio group.

Conclusions

Maternal digit ratio was negatively associated with offspring sex ratio. Females with a lower digit ratio were more likely to have more male offspring compared to those with a higher digit ratio. Thus, our results suggest that the sex of offspring might be more influenced by maternal rather than paternal factors.     

Different Survival of Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma Patients by the Extent of Portal Vein Invasion and the Type of Extrahepatic Spread

Portal vein invasion (PVI) and extrahepatic spread (ES) are two tumor-related factors that define advanced stage in the Barcelona Clinic Liver Cancer (BCLC) staging system (BCLC stage C), and the recommended first line therapy in this stage is sorafenib. However, the extent of PVI and the type of ES may affect patient prognosis as well as treatment outcome. This study analyzed survival of BCLC stage C HCC patients in order to see whether sub-classification of BCLC stage C is necessary. A total of 582 treatment naïve, BCLC stage C HCC patients [age: 54.3 ± 10.8 years, males = 494 (84.9%), hepatitis B virus (458, 78.7%)], defined by PVI and/or ES, were analyzed. Extent of PVI was divided into none, type I-segmental/sectoral branches, type II-left and/or right portal vein, and type III-main portal vein trunk. Type of ES was divided into nodal and distant metastasis. The extent of PVI and type of ES were independent factors for survival. When patients were sub-classified according to the extent of PVI and type of ES, the median survival was significantly different [11.7 months, 5.7 months, 4.9 months and 2.3 months for C1 (PVI-O/I without distant ES), C2 (PVI-II/III without distant ES), C3 (PVI-0/I with distant ES), and C4 (PVI-II/III with distant ES), respectively, P = 0.01]. Patients’ survival was different according to the treatment modality in each sub-stage. Sub-classification of BCLC stage C according to the extent of PVI and type of ES resulted in a better prediction of survival. Also, different outcome was observed by treatment modalities in each sub-stage. Sub-classification of BCLC stage C is required to minimize heterogeneity within the same tumor stage, that will help better predict survival and to select optimal treatment strategies.     

The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses

Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca²⁺ concentration ([Ca²⁺]_i). The phosphorylation of signaling molecules and [Ca²⁺]_i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro.     

Src regulates the activity of SIRT2

SIRT2 is a mammalian member of the Sirtuin family of NAD⁺-dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. c-Src also showed the ability to regulate the deacetylation activity of SIRT2. Investigation on the phosphorylation of SIRT2 suggested that this was the method of c-Src-mediated SIRT2 regulation.     

An immunohistochemical study of the pancreatic endocrine cells of the ddN mouse

The regional distribution and frequency of the pancreatic endocrine cells in the ddN mouse were studied using specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP). In the pancreatic islets, most of insulin-immunoreactive (IR) cells were located in the central region, and glucagon-, somatostatin and hPP-IR cells were located in the peripheral region regardless of the lobe. In the splenic part, glucagon-IR cells were also located in the central regions, and more numerous somatostatin-IR cells were detected in the central regions as compared with the duo-denal part. hPP-IR cells were restricted to the peripheral regions in both lobes but more numerous cells were detected in the duodenal portion. In the exocrine parenchyma of the splenic lobe, only insulin- and glucagon-IR cells were detected but all four kinds of IR cells were observed in the duodenal portion. In addition, insulin and hPP-IR cells were also demonstrated in the pancreatic duct regions. In conclusion, some strain-dependent characteristic distributional patterns of pancreatic endocrine cells were found in the ddN mouse with somewhat different distributional patterns between the two pancreatic lobes.     

Early predictors of cardiac decompensation in experimental volume overload

The adaptation to chronic hypoxia confers long-lasting cardiac protection against acute ischemia–reperfusion injury. Protein kinase C (PKC) appears to play a role in the cardioprotective mechanism but the involvement of individual PKC isoforms remains unclear. The aim of this study was to examine the effects of chronic intermittent hypoxia (CIH; 7,000 m, 8 h/day) and acute administration of PKC-δ inhibitor (rottlerin, 0.3 mg/kg) on the expression and subcellular distribution of PKC-δ and PKC-ε in the left ventricular myocardium of adult male Wistar rats by Western blot and quantitative immunofluorescence microscopy. CIH decreased the total level of PKC-ε in homogenate without affecting the level of phosphorylated PKC-ε (Ser729). In contrast, CIH up-regulated the total level of PKC-δ as well as the level of phosphorylated PKC-δ (Ser643) in homogenate. Rottlerin partially reversed the hypoxia-induced increase in PKC-δ in the mitochondrial fraction. Immunofluorescent staining of ventricular cryo-sections revealed increased co-localization of PKC-δ with mitochondrial and sarcolemmal membranes in CIH hearts that was suppressed by rottlerin. The formation of nitrotyrosine as a marker of oxidative stress was enhanced in CIH myocardium, particularly in mitochondria. The expression of total oxidative phosphorylation complexes was slightly decreased by CIH mainly due to complex II decline. In conclusion, up-regulated PKC-δ in CIH hearts is mainly localized to mitochondrial and sarcolemmal membranes. The inhibitory effects of rottlerin on PKC-δ subcellular redistribution and cardioprotection (as shown previously) support the view that this isoform plays a role in the mechanism of CIH-induced ischemic tolerance.