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Machine Learning Ensemble Investigates Age in the Transcriptomic Response to Spaceflight in Murine Mammary Tissue: Observational Study

2026-01-14T13:45:09-05:00

Background: Spaceflight presents unique environmental stressors, such as microgravity and radiation, that significantly affect biological systems at the molecular, cellular, and organismal levels. Astronauts face an increased risk of developing cancer due to exposure to ionizing radiation and other spaceflight-related factors. Age plays a crucial role in the body’s response to the cellular stresses that lead to cancer, with younger organisms generally exhibiting more efficient response mechanisms than older ones. The vast majority of research investigating breast cancer risk from spaceflight uses cell lines exposed to simulated radiation and microgravity, but cell lines cannot capture the combinatorial response expressed across tissues, organs, and systems to real radiation and microgravity in space. Objective: The primary objective of this in silico observational study is to characterize the molecular response to spaceflight of in vivo murine mammary tissue. We use an ensemble of linear binary classifiers to identify the molecular biomarkers enriched in this response using mice flown on the International Space Station. The secondary objective is to determine if age plays a role in this response. Methods: The NASA Open Science Data Repository (OSDR) has curated transcriptomic data obtained from 10 BALB/cAnNTac female mice flown on the International Space Station and 33 control mice kept on earth (OSD-511). In this observational study focused on two age groups (old/young), we utilized an ensemble of four machine learning binary classifiers with linear decision boundaries (logistic regression, support vector machine, stochastic gradient descent, and single-layer perceptron) to analyze gene expression profiles to predict age (old vs young) and condition (spaceflight vs ground control). Using the genes our ensemble identified as most predictive, we performed pathway enrichment analysis to investigate the molecular pathways involved in spaceflight-related health risks, particularly in the context of breast cancer. Results: The pathway enrichment analyses revealed age-differentiated responses to spaceflight (false discovery rate–adjusted q-values < .05). Among the 10 mice flown in space, younger mice exhibited significantly enriched pathways related to lipid metabolism and inflammatory stress signaling. All spaceflown mice demonstrated evidence of adaptation in retinoid metabolism and Peroxisome proliferator-activated receptor (PPAR) signaling in response to microgravity and radiation relative to their 33 ground control counterparts. Conclusions: Spaceflight-induced breast cancer risk manifests through distinct age-specific mechanisms: younger individuals face risk through maladaptive metabolic hyperactivity and oxidative cycling; while older individuals are vulnerable due to impaired stress responses and accumulated metabolic dysfunction. Both age groups ultimately face elevated carcinogenic potential through different but converging pathways. These findings highlight the critical role of age in modulating the response to spaceflight-induced stress and suggest that these molecular pathways may contribute to differential outcomes in tissue homeostasis, metabolic disorders, and breast cancer susceptibility.

Authors’ Response to Peer Reviews of “Machine Learning Ensemble Investigates Age in the Transcriptomic Response to Spaceflight in Murine Mammary Tissue: Observational Study”

2026-01-14T13:45:09-05:00

This is the author(s)' response to peer review reports related to "Machine Learning Ensemble Investigates Age in the Transcriptomic Response to Spaceflight in Murine Mammary Tissue: An Observational Study"

Peer Review of “Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study”

2026-01-08T15:45:07-05:00

This is a peer review report related to "Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study"

Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study

2026-01-08T15:45:07-05:00

Background: Lettuce (Lactuca sativa L.) is an economically important leafy vegetable that is cultivated worldwide. Advances in plant biotechnology have enabled the development of transgenic and transplastomic lettuce lines with specific agronomic traits that produce pharmaceutical proteins and biological compounds. Plant regeneration efficiency is a critical and highly cultivar-dependent step in plant genetic transformation. No morphological markers have been identified that predict the regeneration ability or cytokinin requirement in lettuce cultivars, hindering the establishment of efficient regeneration systems. Objective: This study aimed to optimize the direct shoot regeneration efficiency in leaf lettuce cultivars and identify a morphological trait that predicts the optimal cytokinin concentration for each cultivar. Methods: The direct shoot regeneration of two cultivars (Chima-sanchi and Chirimen-chisya) was tested on media containing various concentrations of the cytokinin, 6-benzylaminopurine (BAP). Four additional cultivars with different seed coat colors were analyzed to determine the relationship between seed coat color and the optimal BAP concentration. Statistical significance was evaluated using Student’s t-test, with significance set at P<.01. Results: The highest regeneration efficiencies in Chima-sanchi (80.5 ± 3.0%; 103 of 128 explants) and Chirimen-chisya (50.0 ± 4.4%; 64 of 128 explants) were 0.05 and 0.5 mg/L BAP, respectively. Therefore, the optimal BAP concentration significantly differed between the cultivars (P<.01). The seed coat color and the optimal BAP concentration required for efficient direct shoot regeneration were strongly correlated among the six cultivars. Conclusions: Seed coat color is a useful morphological marker for predicting the optimal BAP concentration required for efficient direct shoot regeneration in leaf lettuce cultivars. These findings contribute to optimizing lettuce shoot regeneration systems for specific cultivars.

Peer Review of “Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study”

2026-01-08T15:45:07-05:00

This is a peer review report related to "Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study"

Authors’ Response to Peer Reviews of “Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study”

2026-01-08T15:45:07-05:00

This is the author(s)' response to peer review reports related to "Relationship Between Seed Coat Color and Cytokinin Concentration in Efficiently Regenerating Leaf Lettuce Shoots: In Vitro Experimental Study"

Authors’ Response to Peer Reviews of “Population Interaction in the Jōmon Society via 3D Data of Human Crania: Geometric Morphometric Study”

2025-11-12T14:15:04-05:00

This is the author(s)' response to peer review reports related to "Population interaction in the Jōmon society via three-dimensional data of human crania: Geometric morphometric study"

Population Interaction in the Jōmon Society via 3D Data of Human Crania: Geometric Morphometric Study

2025-11-12T14:15:04-05:00

Background: Anthropologists have extensively discussed the population history in the Jōmon period of the Japanese archipelago (14,000 to 800 cal BC, incipient), when people engaged mainly in hunting and gathering. Some have supported the notion of relative uniformity within the Jōmon population, which could be sustained by widespread population interactions, although others have claimed that spatiotemporal differences may exist to some extent. Objective: The aim of the present study is to examine the morphological variations within and between regional populations to investigate the population interactions in the period. Methods: The present study employs geometric morphometrics of larger samples of three-dimensional data of Jōmon human crania (N = 363, including 146 females, 215 males and two unknown-sex individuals) from 97 sites than previous studies. Results: The results show that morphological variations are more pronounced within individual populations especially in the principal component one, relating to the facial width, degree of prognathism, and location of occipital areas, in contrast to the relatively smaller variations observed between different phases and geographical regions. Conclusions: This observation is consistent with the possibility that the population interactions of the Jōmon people had been widespread and continuous, and which has an important implication for their resilience against severe climate changes at that time: The relative stability of the Jōmon society might be sustained by their frequent interactions with various populations, as suggested by insights from relevant archaeological, ethnographic, and genetic research.

Peer Review of “Population Interaction in the Jōmon Society via 3D Data of Human Crania: Geometric Morphometric Study”

2025-11-12T14:15:04-05:00

This is a peer review report related to "Population interaction in the Jōmon society via three-dimensional data of human crania: Geometric morphometric study"

Peer Review of “Population Interaction in the Jōmon Society via 3D Data of Human Crania: Geometric Morphometric Study”

2025-11-12T14:15:04-05:00

This is a peer review report related to "Population interaction in the Jōmon society via three-dimensional data of human crania: Geometric morphometric study"