Mechanisms of sex determination and X-chromosome dosage compensation

Abnormalities in chromosome number have the potential to disrupt the balance of gene expression and thereby decrease organismal fitness and viability. Such abnormalities occur in most solid tumors and also cause severe developmental defects and spontaneous abortions. In contrast to the imbalances in chromosome dose that cause pathologies, the difference in X-chromosome dose used to determine sexual fate across diverse species is well tolerated. Dosage compensation mechanisms have evolved in such species to balance X-chromosome gene expression between the sexes, allowing them to tolerate the difference in X-chromosome dose. This review analyzes the chromosome counting mechanism that tallies X-chromosome number to determine sex (XO male and XX hermaphrodite) in the nematode Caenorhabditis elegans and the associated dosage compensation mechanism that balances X-chromosome gene expression between the sexes. Dissecting the molecular mechanisms underlying X-chromosome counting has revealed how small quantitative differences in intracellular signals can be translated into dramatically different fates. Dissecting the process of X-chromosome dosage compensation has revealed the interplay between chromatin modification and chromosome structure in regulating gene expression over vast chromosomal territories.

Short-Time Changes of Intraocular Pressure and Biomechanics of the Anterior Segment of the Eye during Water Drinking Test in Patients with XEN GelStent

Purpose: Little is known about short-term changes in intraocular pressure (IOP) following minimally invasive glaucoma surgeries, such as post-XEN GelStent implantation. Although the importance of corneal biomechanics in glaucoma diagnostics has been reported, little work has been conducted on postoperative description of changes when the structure of the anterior segment is altered. The aim of presented study was to evaluate the changes in the biomechanical parameters of the anterior segment of the post-XEN GelStent implantation eyes. Patients and Methods: This investigator-initiated, open-label, prospective, single-center study recruited patients. Patients with primary open-angle glaucoma (POAG) after XEN GelStent implantation versus matched POAG controls (considered as control group/CG) treated pharmacologically were screened. Water loading was conducted using 10 mL of water per kilogram of body weight for ≤5 min. Goldmann applanation tonometry (GAT), corneal hysteresis (CH), and corneal resistance factor (CRF) were performed before water loading and after every 15 min up to 1 h. Results: The water drinking test (WDT) was positive in 3.7% (1 out of 27) of patients in the post-XEN group compared with 22.7% (5 out of 22) of patients in the control group (CG; p < 0.05). Mean fluctuations in GAT during the WDT were higher in the CG group (3.6 ± 2.5 mmHg vs. 2.9 ± 1.3 mmHg, p < 0.001). CRF and CH changed significantly only in the post-XEN group. The mean peak of CH and CRF occurred at 15 and 30 min of the test in the post-XEN group (p = 0.001). Conclusion: WDT is important to assess the ability of compensation mechanisms to reduce fluctuations in IOP after water upload. The relationship between biomechanics of the anterior segment and glaucoma may have substantial impact on surgical outcome evaluation.

Cysteine-Rich Secretory Proteins (CRISP) are Key Players in Mammalian Fertilization and Fertility

Mammalian fertilization is a complex process involving a series of successive sperm-egg interaction steps mediated by different molecules and mechanisms. Studies carried out during the past 30 years, using a group of proteins named CRISP (Cysteine-RIch Secretory Proteins), have significantly contributed to elucidating the molecular mechanisms underlying mammalian gamete interaction. The CRISP family is composed of four members (i.e., CRISP1-4) in mammals, mainly expressed in the male tract, present in spermatozoa and exhibiting Ca2+ channel regulatory abilities. Biochemical, molecular and genetic approaches show that each CRISP protein participates in more than one stage of gamete interaction (i.e., cumulus penetration, sperm-ZP binding, ZP penetration, gamete fusion) by either ligand-receptor interactions or the regulation of several capacitation-associated events (i.e., protein tyrosine phosphorylation, acrosome reaction, hyperactivation, etc.) likely through their ability to regulate different sperm ion channels. Moreover, deletion of different numbers and combination of Crisp genes leading to the generation of single, double, triple and quadruple knockout mice showed that CRISP proteins are essential for male fertility and are involved not only in gamete interaction but also in previous and subsequent steps such as sperm transport within the female tract and early embryo development. Collectively, these observations reveal that CRISP have evolved to perform redundant as well as specialized functions and are organized in functional modules within the family that work through independent pathways and contribute distinctly to fertility success. Redundancy and compensation mechanisms within protein families are particularly important for spermatozoa which are transcriptionally and translationally inactive cells carrying numerous protein families, emphasizing the importance of generating multiple knockout models to unmask the true functional relevance of family proteins. Considering the high sequence and functional homology between rodent and human CRISP proteins, these observations will contribute to a better understanding and diagnosis of human infertility as well as the development of new contraceptive options.

How did the Sarbanes–Oxley Act affect managerial incentives? Evidence from corporate acquisitions

We examine the impact of incentive compensation on the riskiness of acquisition decisions before and after the passage of the Sarbanes–Oxley Act (SOX). Before SOX, equity-based compensation was positively related to changes in risk around acquisition decisions, but this relationship weakened after the introduction of SOX. The drop in post-SOX acquisition-related risk stems from how managers respond to compensation-based incentives in the new regulatory environment. We show that executive stock options and pay-risk sensitivity drive post-SOX managerial responsiveness to risk-taking incentives. We also document a post-SOX value-enhancing effect on long-term stock-price performance and total factor productivity through these same incentive compensation mechanisms. The results are robust to selection bias, simultaneity, measurements of risk, and the definition of incentive compensation.

Organizational, Economic, and Strategic Aspects of Capitalization of Multipurpose Forest Industries

Introduction. The present article forecasts the organizational, economic, and strategic aspects of the multifunctional forestry capitalization in the Kemerovo region aka Kuzbass. The authors analyzed the current Russian laws in order to answer the following question: is multi-purpose forest utilization able to ensure the rights and interests of all its participants, while providing legal means to resolve various related issues? Study objects and methods. The research featured the legal norms in the field of forest, wildlife, and subsoil utilization. The authors assessed their ability to guarantee sustainable use of natural resources while protecting the rights and legitimate interests of forest users. The study was based on general standard methods of cognition and special legal methods. Results and discussion. Hunting is regulated by hunting sector agreements. The Forest Code and the Hunting Law of the Russian Federation do not prohibit or restrict other types of forest utilization of hunting grounds. Most Western European countries link land ownership to hunting rights, which makes landowners liable for damage caused by hunting and obliged to protect the local fauna. Conclusion. Russian legislation does not provide for direct conciliation and compensation mechanisms in cases a part of hunting ground is used for other purposes, e.g. mining. Russian legislation needs legal termination procedures for hunting sector agreements and compensation rules in case a land plot was seized from hunting providers for subsoil use.

Etiology, diagnosis, and treatment of iatrogenic spinal deformity

Background: Spinal fusion is a common procedure that provides spinal stability by connecting vertebral segments using a bone graft. Because the spinal alignment is fixed permanently after spinal fusion, a mal-aligned fusion can produce iatrogenic spinal deformity and imbalance with significant disability.Current Concepts: Failure to restore adequate segmental lordosis in lumbar spinal fusion is a common cause of iatrogenic spine deformity. Local and regional spinal deformities can affect the global alignment; accordingly, spinal imbalance can occur when the compensation mechanisms fail. Diagnosis and surgical planning should be made on a thorough analysis of global and spinopelvic parameters on the standing whole-spine radiographs. Surgical treatment includes neural decompression, spinal fusion, and deformity correction. Spinal osteotomy provides a favorable surgical outcome, although the complication rate is high.Discussion and Conclusion: Iatrogenic spine deformity is increasing due to the increased occurrence of spinal fusion surgery. To prevent iatrogenic spine deformity, the index fusion surgery should be performed based on a comprehensive analysis of spinopelvic alignment and balance.

Neuronal activity reorganization in motor cortex for successful locomotion after a lesion in the ventrolateral thalamus

Thalamic stroke leads to ataxia if the cerebellum-receiving ventrolateral thalamus (VL) is affected. The compensation mechanisms for this deficit are not well understood, particularly the roles that single neurons and specific neuronal subpopulations outside the thalamus play in recovery. The goal of this study was to clarify neuronal mechanisms of the motor cortex involved in mitigation of ataxia during locomotion when part of the VL is inactivated or lesioned. In freely ambulating cats, we recorded the activity of neurons in layer V of the motor cortex as the cats walked on a flat surface and horizontally placed ladder. We first reversibly inactivated approximately 10% of the VL unilaterally using glutamatergic transmission antagonist CNQX and analyzed how the activity of motor cortex reorganized to support successful locomotion. We next lesioned 50-75% of the VL bilaterally using kainic acid and analyzed how the activity of motor cortex reorganized when locomotion recovered. When a small part of the VL was inactivated, the discharge rates of motor cortex neurons decreased, but otherwise the activity was near normal, and the cats walked fairly well. Individual neurons retained their ability to respond to the demand for accuracy during ladder locomotion; however, most changed their response. When the VL was lesioned, the cat walked normally on the flat surface but was ataxic on the ladder for several days post-lesion. When ladder locomotion normalized, neuronal discharge rates on the ladder were normal, and the shoulder-related group was preferentially active during the stride's swing phase.