High Bone Mass Disorders : New Insights From Connecting the Clinic and the Bench

Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease-causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics can shape discovery of novel HBM genes and/or mechanisms in the future, through implementation of omics assessments in existing and future model systems. Finally, we address strategies to improve gene identification in unsolved HBM cases and highlight the importance for cross-laboratory collaborations encompassing multidisciplinary efforts to transfer knowledge generated at the bench to the clinic. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

High Bone Mass Disorders: New Insights from Connecting the Clinic and the Bench

Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease-causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics can shape discovery of novel HBM genes and/or mechanisms in the future, through implementation of omics assessments in existing and future model systems. Finally, we address strategies to improve gene identification in unsolved HBM cases and highlight the importance for cross-laboratory collaborations encompassing multidisciplinary efforts to transfer knowledge generated at the bench to the clinic.Acknowledgements: This publication is initiated upon work from the European Cooperation for Science and Technology (COST) Action GEMSTONE, supported by COST. COST is a funding agency for research and innovation networks. Our Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation (www.cost.eu). We therefore thank current and former members of the COST GEMSTONE Working Group 3 (https://cost-gemstone.eu/working-groups/wg3-monogenic-conditions-human-ko-models/) for discussions and support during manuscript preparation. All figures in this manuscript were created with BioRender.com

Carbon dioxide/brine wettability of porous sandstone versus solid quartz: An experimental and theoretical investigation

Hypothesis: Wettability plays an important role in underground geological storage of carbon dioxide because the fluid flow and distribution mechanism within porous media is controlled by this phenomenon. CO 2 pressure, temperature, brine composition, and mineral type have significant effects on wettability. Despite past research on this subject, the factors that control the wettability variation for CO 2 /water/minerals, particularly the effects of pores in the porous substrate on the contact angle at different pressures, temperatures, and salinities, as well as the physical processes involved are not fully understood. Experiments: We measured the contact angle of deionised water and brine/CO 2 /porous sandstone samples at different pressures, temperatures, and salinities. Then, we compared the results with those of pure quartz. Finally, we developed a physical model to explain the observed phenomena. Findings: The measured contact angle of sandstone was systematically greater than that of pure quartz because of the pores present in sandstone. Moreover, the effect of pressure and temperature on the contact angle of sandstone was similar to that of pure quartz. The results showed that the contact angle increases with increase in temperature and pressure and decreases with increase in salinity

Association of various reproductive rights, domestic violence and marital rape with depression among Pakistani women

<p>Abstract</p> <p>Background</p> <p>Depression among women is common in developing countries. Gender inequality can contribute to women's risk for depression. Lack of reproductive and sexual rights is an important marker of gender inequality and women do not have the freedom to express their reproductive and sexual needs in many parts of the world. Therefore we designed this study to determine the association of depression with lack of various reproductive rights and domestic violence among married women in Karachi, Pakistan.</p> <p>Methods</p> <p>A case-control study with 152 cases and 152 controls, which included women 15-48 years, recruited from two teaching hospitals from 1^stJune 2007 through 31^stAugust 2007. The SRQ was administered to all subjects. A cut off score of 8 was used to confirm cases of depression diagnosed by physicians, and to exclude cases of depression from the controls. Self-administered questionnaire was used to assess the risk factors.</p> <p>Results</p> <p>61% of the cases and 43% of the controls were ever abused by spouse and the frequency of marital rape was 33% in cases and 13% in controls. After adjusting for the effects of other variables in the model, less than 18 years of age at marriage (OR 2.00; 95% CI = 1.07, 3.7), decision for marriage by parents (OR 3.51; 95% CI = 1.67, 7.37), abuse by in laws (OR 4.91; 95% CI = 2.66, 9.06), ≤ 3 hours per day spent with husband (OR 2.33; 95% CI = 1.34, 4.08), frequency of intercourse ≤ 2 times per week (OR 1.85; 95% CI = 1.06, 3.22) and marital rape (OR 3.03; 95% CI = 1.50, 6.11) were associated with depression among women.</p> <p>Conclusion</p> <p>In our study depression in married women was associated with younger age at marriage, lack of autonomy in marriage decisions, marital rape and domestic abuse by in-laws. Efforts should be directed towards creating awareness about the reproductive and sexual rights of women in Pakistan. Physicians should be trained to screen and identify women who may be at risk for psychological distress as a result of denial of reproductive rights so that they can support positive mental health outcomes through individual, family or marital counseling.</p

The nature and fate of natural resins in the geosphere. XII. Investigation of C-ring aromatic diterpenoids in Raritan amber by pyrolysis-GC-matrix isolation FTIR-MS

Upper Cretaceous amber from the Raritan Formation (Sayerville, New Jersey) has been investigated by Pyrolysis-GC-MS and Pyrolysis-GC-matrix isolation FTIR-MS. Results establish the existence of two distinct forms of amber in this deposit. Both forms are Class Ib ambers, but they are unambiguously differentiated on the basis of their (intact) diterpenoid composition. The presence of callitrisate in both forms, and cupraene in samples designated form 1, strongly suggest that both derive from related-but-distinct species within the Cupressaceae. In addition to callitrisate, dehydroabietate and analogous 17-nor-, 16,17-dinor- and 15,16,17-trinor- analogues of these compounds are also observed. The distributions of these products in multiple samples suggest that they are the result of biological emplacement, rather than diagenetic modification of the parent compounds. This indicates that the distributions of diterpenes observed in these samples are representative of the original bioterpenoids and, hence, are useful for chemotaxonomic analyses

Mental Toughness and Individual Differences in Learning, Educational and Work Performance, Psychological Well-being, and Personality: A Systematic Review

Mental toughness (MT) is an umbrella term that entails positive psychological resources, which are crucial across a wide range of achievement contexts and in the domain of mental health. We systematically review empirical studies that explored the associations between the concept of MT and individual differences in learning, educational and work performance, psychological well-being, personality, and other psychological attributes. Studies that explored the genetic and environmental contributions to individual differences in MT are also reviewed. The findings suggest that MT is associated with various positive psychological traits, more efficient coping strategies and positive outcomes in education and mental health. Approximately 50% of the variation in MT can be accounted for by genetic factors. Furthermore, the associations between MT and psychological traits can be explained mainly by either common genetic or non-shared environmental factors. Taken together, our findings suggest a ‘mental toughness advantage’ with possible implications for developing interventions to facilitate achievement in a variety of settings

Osteochondral defects in the ankle: why painful?

Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage

Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System

Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain