Amorphous calcium carbonate enhances osteogenic differentiation and myotube formation of human bone marrow derived mesenchymal stem cells and primary skeletal muscle cells under microgravity conditions.

Astronauts are exposed to severely stressful physiological conditions due to microgravity and increased space radiation. Space environment affects every organ and cell in the body and the significant adverse effects of long-term weightlessness include muscle atrophy and deterioration of the skeleton (spaceflight osteopenia). Amorphous Calcium Carbonate (ACC) emerges as a promising candidate for prevention of these effects, owing to its unique physicochemical properties and its potential to address the intricately linked nature of bone-muscle crosstalk. Reported here are two studies carried out on the International Space Station (ISS). The first, performed in 2018 as a part of the Ramon-Spacelab project, was a preliminary experiment, in which stromal murine cells were differentiated into osteoblasts when ACC was added to the culture medium. A parallel experiment was done on Earth as a control. The second study was part of Axiom-1's Rakia project mission launched to the ISS on 2022 utilizing organ-on-a-chip methodology with a specially designed autonomous module. In this experiment, human bone-marrow derived mesenchymal stem cells (hBM-MSCs) and human primary muscle cells were cultured in the presence or absence of ACC, in duplicates. The results showed that ACC enhanced differentiation of human primary skeletal muscle cells into myotubes. Similarly, hBM-MSCs were differentiated significantly better into osteocytes in the presence of ACC leading to increased calcium deposits. The results, combined with previous data, support the use of ACC as an advantageous supplement for preventing muscle and bone deterioration in outer space conditions, facilitating extended extraterrestrial voyages and colonization.

Brook Rearrangement as Trigger for Dearomatization Reaction: Synthesis of Non-Aromatic N-Heterocycles.

The [1,2]-Brook rearrangement stands as a potent technique for constructing complex molecules. In this study, we showcase its power in the dearomatization of aromatic N-heterocycles. Through a concise four-step process that integrates lithiation, nucleophilic addition, Brook rearrangement and dearomatization reaction, we demonstrate a versatile strategy for generating diverse non-aromatic N-heterocycles which exhibit ambident reactivities. Various acyl silanes, halo-pyridines, and quinolines have been explored within this context. The synthetic utility of this methodology is demonstrated through the construction of complex architectures.

Amorphous Calcium Carbonate Shows Anti-Cancer Properties That are Attributed to Its Buffering Capacity.

AIM: Amorphous calcium carbonate (ACC) is a non-crystalline form of calcium carbonate, and it is composed of aggregated nano-size primary particles. Here, we evaluated its anti-cancer effect postulated relative to its buffering capabilities in lung cancer. METHODS: Tumors were evaluated in vivo using the Lewis lung carcinoma (LLC) mouse cell line and A549 human lung cancer carcinoma cell line. LLC and A549 cells were injected subcutaneously into the right hind leg of mice. Treatments (ACC, cisplatin, vehicle, and ACC with cisplatin, all given via daily IP injections) started once tumors reached a measurable size. Treatments were carried out for 14 days in the LLC model and for 22 and 24 days in the xenograft model (two experiments). LLC tumors were resected from ACC at the end of the study, and vehicle groups were evaluated for cathepsin B activity. Differential gene expression was carried out on A549 cells following 8 weeks of in vitro culture in the presence or absence of ACC in a culture medium. RESULTS: The ACC treatment decelerated tumor growth rates in both models. When tumor volumes were compared on the last day of each study, the ACC-treated animal tumor volume was reduced by 44.83% compared to vehicle-treated animals in the LLC model. In the xenograft model, the tumor volume was reduced by 51.6% in ACC-treated animals compared to vehicle-treated animals. A more substantial reduction of 74.75% occurred in the combined treatment of ACC and cisplatin compared to the vehicle (carried out only in the LLC model). Cathepsin B activity was significantly reduced in ACC-treated LLC tumors compared to control tumors. Differential gene expression results showed a shift towards anti-tumorigenic pathways in the ACC-treated A549 cells. CONCLUSION: This study supports the ACC anti-malignant buffering hypothesis by demonstrating decelerated tumor growth, reduced cathepsin B activity, and altered gene expressions to produce anti-cancerous effects.

Effect of Contact Lens Design on Objective Visual Acuity-Based Parameters in Pre-Presbyopic Patients in Photopic and Mesopic Lighting Conditions.

Presbyopia is often corrected by progressive soft contact lenses (CL), and the resulting visual acuity-based parameters can be affected by the lens design and pupil size under different lighting conditions. In this study, we examined the effect of CL design (spheric vs. aspheric) on objective parameters of visual acuity-based parameters under mesopic vs. photopic lighting conditions. In a prospective, double-blind study, pre-presbyopic and presbyopic patients were fitted with spheric (Dispo Silk; 8.6 base curve, 14.2 diameter) and aspheric (Dispo Aspheric; 8.4 base curve, 14.4 diameter) CLs. The low contrast (10%) and high contrast (100%) visual acuity (VA), amplitude of accommodation (AA) (push-away method, Diopters) and distance contrast sensitivity (CS) (FACT chart, cycles per degree (CPD)) were measured with both types of CLs under mesopic and photopic lighting conditions. The eye with the better visual acuity was tested and analyzed. Thirteen patients (age range: 38-45 years) were included. The mean CS was significantly better with spheric compared to aspheric lenses for low spatial frequencies (3 CPD: 81.69 ± 7.86, 67.62 ± 5.67, respectively; p < 0.05), though there was no significant difference for lower or higher spatial frequencies (1.5, 6, 12, 18 CPD). The low-contrast (10%) and high-contrast (100%) VAs were not different between the two lens designs. However, there were significant differences between near VA, distance low-contrast VA and AA obtained under mesopic (dim) vs. photopic (bright) conditions with the aspheric design correction modality. In conclusion, photopic lighting conditions improved both the visual acuity and measured amplitude of accommodation with both lens designs, though the amplitude of accommodation was significantly higher with aspheric lenses. However, contrast sensitivity demonstrated the superiority of the spheric lens at a 3 CPD spatial frequency. This suggests that the ideal lens differs from patient to patient, depending on the visual demands.

Adherence to referrals from preschool vision screening and identification of barriers for non-adherence in Israel.

CLINICAL RELEVANCE: Preschool vision screening is essential for the early detection and treatment of eye and vision problems. BACKGROUND: The rate of parental adherence to referrals for comprehensive examination was assessed and factors and potential barriers associated with adherence were identified. METHODS: In a prospective cohort study design, parents were offered to bring their 3-6 year old aged children to free-of-charge vision screening tests at community-based Mother Child Health Centers. Children with abnormal findings were referred to an ophthalmologist examination. Parents were interviewed three to six months after the referral to evaluate adherence and barriers. Barriers were organised into a conceptual framework of parental predisposing and health system factors. Adherence and barriers were assessed by sex, age, ethnic group and socio-economic-status. RESULTS: Altogether 1283 children (mean age 4.5 ± 0.6 years, 47.8% girls) were screened in the Jerusalem district, Israel. The ethnic groups, Jewish (ultra-Orthodox 51.4%, secular/religious 33.2%) and Arab (15.4%), were similar by age and sex, but not by socio-economic status. The overall referral rate was 23.0% (N = 295). Referral rate was not associated with demographic factors. Overall, 54.3% (N = 160) of parents adhered to the referral to bring the child for a full eye examination. Adherence did not differ with sex, ethnicity or socio-economic-status. Parents of 5-6-year-old children were significantly more likely to adhere than parents of younger children. Of parents who did not adhere, 79.3% were attributed to predisposing factors, 16.3% to system factors and 4.4% to other reasons. CONCLUSIONS: Only half the parents proceeded with the recommended full eye examination. Parents of older children were more likely to adhere to referral. In contrast with vaccinations provided by Mother Child Health Centers, adherence to vision screening did not vary based on ethnicity or socio-economic factors. Since most barriers were associated with predisposing factors of parents, interventions to improve adherence should include parental education.

Sulfonium cations as versatile strongly π-acidic ligands.

More than a century old, sulfonium cations are still intriguing species in the landscape of organic chemistry. On one hand they have found broad applications in organic synthesis and materials science, but on the other hand, while isoelectronic to the ubiquitous tertiary phosphine ligands, their own coordination chemistry has been neglected for the last three decades. Here we report the synthesis and full characterization of the first Rh(i) and Pt(ii) complexes of sulfonium. Moreover, for the first time, coordination of an aromatic sulfonium has been established. A thorough computational analysis of the exceptionally short S-Rh bonds obtained attests to the strongly π-accepting nature of sulfonium cations and places them among the best π-acceptor ligands available today. Our calculations also show that embedding within a pincer framework enhances their π-acidity even further. Therefore, in addition to the stability and modularity that these frameworks offer, our pincer complexes might open the way for sulfonium cations to become powerful tools in π-acid catalysis.

Grief and growth of bereaved siblings as related to attachment style and flexibility.

This study examined the relationship between attachment style, coping flexibility, military/non-military cause of death, levels of grief reactions and posttraumatic growth (PTG), in 150 bereaved adult siblings in Israel. Insecurely attached participants, 72% of the sample, reported more grief and less PTG than did securely attached ones. Highly avoidant individuals exhibited the least amount of PTG. Securely attached siblings were more flexible and flexibly coping participants reported less grief and higher PTG. Cause of death was not related to grief and PTG. Discussion of these findings yields conditions enabling PTG after a sibling loss.

Others' anger makes people work harder not smarter: the effect of observing anger and sarcasm on creative and analytic thinking.

The authors examine whether and how observing anger influences thinking processes and problem-solving ability. In 3 studies, the authors show that participants who listened to an angry customer were more successful in solving analytic problems, but less successful in solving creative problems compared with participants who listened to an emotionally neutral customer. In Studies 2 and 3, the authors further show that observing anger communicated through sarcasm enhances complex thinking and solving of creative problems. Prevention orientation is argued to be the latent variable that mediated the effect of observing anger on complex thinking. The present findings help reconcile inconsistent findings in previous research, promote theory about the effects of observing anger and sarcasm, and contribute to understanding the effects of anger in the workplace.

Metabolic buffering exerted by macromolecular crowding on DNA-DNA interactions: origin and physiological significance.

Crowding, which characterizes the interior of all living cells, has been shown to dramatically affect biochemical processes, leading to stabilization of compact morphologies, enhanced macromolecular associations, and altered reaction rates. Due to the crowding-mediated shift in binding equilibria toward association, crowding agents were proposed to act as a metabolic buffer, significantly extending the range of intracellular conditions under which interactions occur. Crowding may, however, impose a liability because, by greatly and generally enhancing macromolecular association, it can lead to irreversible interactions. To better understand the physical determinants and physiological consequences of crowding-mediated buffering, we studied the effects of crowding, or excluded volume, on DNA structures. Results obtained from isothermal titration calorimetry (ITC) and UV melting experiments indicate that crowding-induced effects are marginal under conditions that a priori favor association of DNA strands but become progressively larger when conditions deteriorate. As such, crowding exerts "genuine" buffering activity. Unexpectedly, crowding-mediated effects are found to include enthalpy terms that favorably contribute to association processes. We propose that these enthalpy terms and preferential stabilization derive from a reconfiguration of DNA hydration that occurs in dense DNA-rich phases obtained in crowded environments.

Unique condensation patterns of triplex DNA: physical aspects and physiological implications.

Triple-stranded DNA structures can be formed in living cells, either by native DNA sequences or following the application of antigene strategies, in which triplex-forming oligonucleotides are targeted to the nucleus. Recent studies imply that triplex motifs may play a role in DNA transcription, recombination and condensation processes in vivo. Here we show that very short triple-stranded DNA motifs, but not double-stranded segments of a comparable length, self-assemble into highly condensed and ordered structures. The condensation process, studied by circular dichroism and polarized-light microscopy, occurs under conditions that mimic cellular environments in terms of ionic strength, ionic composition and crowding. We argue that the unique tendency of triplex DNA structures to self-assemble, a priori unexpected in light of the very short length and the large charge density of these motifs, reflects the presence of strong attractive interactions that result from enhanced ion correlations. The results provide, as such, a direct experimental link between charge density, attractive interactions between like-charge polymers and DNA packaging. Moreover, the observations strongly support the notion that triple-stranded DNA motifs may be involved in the regulation of chromosome organization in living cells.