Immune Checkpoint Molecules in Reproductive Immunology

Immune checkpoint molecules, like CTLA-4, TIM-3, PD-1, are negative regulators of immune responses to avoid immune injury. Checkpoint regulators are thought to actively participate in the immune defense of infections, prevention of autoimmunity, transplantation, and tumor immune evasion. Maternal-fetal immunotolerance represents a real immunological challenge for the immune system of the mother: beside acceptance of the semiallogeneic fetus, the maternal immune system has to be prepared for immune defense mostly against infections. In this particular situation, the role of immune checkpoint molecules could be of special interest. In this review, we describe current knowledge on the role of immune checkpoint molecules in reproductive immunology

The Role of Type I and Type II NKT Cells in Materno-Fetal Immunity

NKT cells represent a small but significant immune cell population as being a part of and bridging innate and adaptive immunity. Their ability to exert strong immune responses via cytotoxicity and cytokine secretion makes them significant immune effectors. Since pregnancy requires unconventional maternal immunity with a tolerogenic phenotype, investigation of the possible role of NKT cells in materno-fetal immune tolerance mechanisms is of particular importance. This review aims to summarize and organize the findings of previous studies in this field. Data and information about NKT cells from mice and humans will be presented, focusing on NKT cells characteristics during normal pregnancy in the periphery and at the materno-fetal interface and their possible involvement in female reproductive failure and pregnancy complications with an immunological background

Phenomenological Analysis of Mothers' Perspectives on Relactation in Abdya Regency, Indonesia

The provision of Breast Milk (BM) holds significant implications in the global context, supporting optimal infant health and development. This study employs phenomenological analysis to gain deeper insights into mothers' perspectives and experiences regarding relaxation and restarting breastfeeding after cessation. This method allows for an in-depth exploration of the various facets involving mothers' endeavours to reinstate exclusive breastfeeding practices. The study refers to a global framework encompassing diverse sources, including previous international research, policy documents regarding breastfeeding practices, and qualitative studies from various regions. By amalgamating these perspectives, the research aims to identify common patterns and variations in mothers' views and experiences of relaxation. The findings reveal prominent themes encompassing various crucial aspects. First, a profound comprehension of the multifaceted benefits of exclusive breastfeeding emerges, not only as a source of nutrition but also as a determinant of health, growth, and the emotional bond between mother and infant. Second, family and immediate environment support, including the roles of husbands, mothers-in-law, and other relatives, significantly impact the achievement of successful relactation. Third, guidance and directions provided by healthcare professionals, particularly village midwives and health practitioners, offer essential guidance and understanding for mothers throughout the relactation process.Furthermore, the study portrays certain mothers' personalised and creative approaches while navigating the relactation process. These encompass utilising specific foods and natural elements and sourcing information from various avenues, including the experiences of fellow mothers and official guidelines. In the context of psychological impacts, the study presents an overview of the challenges and sentiments experienced by mothers during relactation, as well as the pivotal role of the emotional bond with the infant in mitigating stress and pressure. Through this phenomenological analysis, the research provides a richer understanding of mothers' viewpoints and experiences in the practice of global-scale relactation. These findings have implications for enhancing societal understanding, family support, and improved healthcare interventions to facilitate and advocate for exclusive breastfeeding practices through relactation. Thus, the study contributes to the global discourse on the significance of Breast Milk in promoting infant health and well-being worldwide

Forest Bathing Always Makes Sense: Blood Pressure-Lowering and Immune System-Balancing Effects in Late Spring and Winter in Central Europe

Various formats of forest bathing have been receiving increasing attention owing to their perspectives in health promotion and the treatment of chronic lifestyle diseases. The majority of field studies are still being conducted in the Far Eastern region, and they often make psychological assessments mainly in the green season. In our pretest–posttest field experiment, twelve healthy, working-age volunteers participated in a 2-h leisurely forest walking program, first in the green season (May) and then in the winter season (January), in the Mecsek Hills, next to Pécs, Hungary. Systolic blood pressure decreased after the trips both in late spring and in the winter. Based on changes in the expressions of CD69, an early activation marker, NKG2D, a major recognition receptor, perforin, granzyme B, and TIM-3, an inhibitory immune checkpoint molecule, on CD8+ cytotoxic T, NK, NKdim, NKbright, and NKT cells, we detected the stimulation of NKbright cells and activation of all examined immune cell subsets in the green season. In the winter, a slight activating and an interesting balancing effect regarding TIM-3 could be observed considering our finding that basal (pretest) TIM-3 expression by NK cells was significantly lower in the winter. Our work expands the knowledge on and potentials of forest medicine

A comprehensive assessment of anthropogenic and natural sources and sinks of Australasia\u27s carbon budget

Regional carbon budget assessments attribute and track changes in carbon sources and sinks and support the development and monitoring the efficacy of climate policies. We present a comprehensive assessment of the natural and anthropogenic carbon (C-CO2) fluxes for Australasia as a whole, as well as for Australia and New Zealand individually, for the period from 2010 to 2019, using two approaches: bottom-up methods that integrate flux estimates from land-surface models, data-driven models, and inventory estimates; and top-down atmospheric inversions based on satellite and in situ measurements. Our bottom-up decadal assessment suggests that Australasia\u27s net carbon balance was close to carbon neutral (−0.4 ± 77.0 TgC yr−1). However, substantial uncertainties remain in this estimate, primarily driven by the large spread between our regional terrestrial biosphere simulations and predictions from global ecosystem models. Within Australasia, Australia was a net source of 38.2 ± 75.8 TgC yr−1, and New Zealand was a net CO2 sink of −38.6 ± 13.4 TgC yr−1. The top-down approach using atmospheric CO2 inversions indicates that fluxes derived from the latest satellite retrievals are consistent within the range of uncertainties with Australia\u27s bottom-up budget. For New Zealand, the best agreement was found with a national scale flux inversion estimate based on in situ measurements, which provide better constrained of fluxes than satellite flux inversions. This study marks an important step toward a more comprehensive understanding of the net CO2 balance in both countries, facilitating the improvement of carbon accounting approaches and strategies to reduce emissions

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe