The O-GlcNAc transferase (OGT) is an essential enzyme that mediates protein O-GlcNAcylation, a unique form of posttranslational modification of many nuclear and cytosolic proteins. Recent studies observed increased OGT and O-GlcNAcylation levels in a broad range of human cancer tissues compared to adjacent normal tissues, indicating a universal effect of OGT in promoting tumorigenesis. Here, we show that OGT is essential for tumor growth in immunocompetent mice by repressing the cyclic GMP-AMP synthase (cGAS)-dependent DNA sensing pathway. We found that deletion of OGT (Ogt-/-) caused a marked reduction in tumor growth in both syngeneic mice tumor models and a genetic mice colorectal cancer (CRC) model induced by mutation of the Apc gene (Apcmin). Pharmacological inhibition or genetic deletion of OGT induced a robust genomic instability (GIN), leading to cGAS-dependent production of the type I interferon (IFN-I) and IFN-stimulated genes (ISGs). As a result, deletion of Cgas or Sting from Ogt-/- cancer cells restored tumor growth, and this correlated with impaired CD8+ T-cell-mediated antitumor immunity. Mechanistically, we found that OGT-dependent cleavage of host cell factor C1 (HCF-1) is required for the avoidance of GIN and IFN-I production in tumors. In summary, our results identify OGT-mediated genomic stability and activate cGAS-STING pathway as an important tumor-cell-intrinsic mechanism to repress antitumor immunity.

Timely goal-oriented behavior is essential for survival and is shaped by experience. In this paper, a multileveled approach was employed, ranging from the polymorphic level through thermodynamic molecular, cellular, intracellular, extracellular, non-neuronal organelles and electrophysiological waves, attesting for signal variability. By adopting Boltzmann's theorem as a thermodynamic conceptualization of brain work, we found deviations from excitation-inhibition balance and wave decoupling, leading to wider signal variability in affective disorders compared to healthy individuals. Recent evidence shows that the overriding on-off design of clock genes paces the accuracy of the multilevel parallel sequencing clocks and that the accuracy of the time-to-action is more crucial for healthy behavioral reactions than their rapidity or delays. In affective disorders, the multilevel clocks run free and lack accuracy of responsivity to environmentally triggered time-to-action as the clock genes are not able to rescue mitochondria organelles from oxidative stress to produce environmentally-triggered energy that is required for the accurate time-to-action and maintenance of the thermodynamic equilibrium. This maintenance, in turn, is dependent on clock gene transcription of electron transporters, leading to higher signal variability and less signal accuracy in affective disorders. From a Boltzmannian thermodynamic and energy-production perspective, the option of reversibility to a healthier time-toaction, reducing entropy is implied. We employed logic gates to show deviations from healthy levelwise communication and the reversed conditions through compensations implying the role of nonneural cells and the extracellular matrix in return to excitation-inhibition balance and accuracy in the time-to-action signaling.

Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.

Digital manufacturing (DM) is actively adopted to the production lifecycles of a variety of critical industries, and this rapid growth has resulted in exponential increase of 3D computer-aided design (CAD) models. Unfortunately, counterfeiting of intellectual property becomes a prominent threat as many 3D designs are accessible online, combined with the proliferation of cheap consumer 3D printers that enable malicious actors to produce non-authentic parts. State-of-the-art techniques to secure manufacturing processes mostly rely on watermarking, which embeds hidden information inside CAD models to prove ownership and authenticity. Nevertheless, such techniques tamper with the model itself, while existing attacks allow removing such watermarks altogether. To address these shortcomings, we integrate signal processing and cryptographic techniques and describe a tailored solution for CAD model ownership and supply chain management. Our approach generates unique identifiers for 3D designs using frequency-domain transforms and employs non-fungible tokens (NFTs) that persist on public distributed ledgers. Our NFTs are implemented on the Ethereum blockchain using smart contracts and their functionality is twofold: (a) authenticate the owner of a CAD model, and (b) enable ownership transfer. To validate our technique, we deployed our smart contract on Ethereum's proof-of-work Ropsten network and demonstrated the applicability of our methodology.

Landing with poor knee sagittal plane biomechanics has been identified as a risk factor for Anterior Cruciate Ligament (ACL) injury. However, it is unclear if the horizontal hop test battery reflects knee function and biomechanics. To investigate the correlation between clinical limb symmetry index (LSI) and landing and propulsion knee biomechanics during the hop test battery using markerless motion capture. Cross-sectional biomechanics laboratory study. Forty-two participants with and without knee surgery (age 28.0 ± 8.0 years) performed the hop test battery which consisted of a single hop for distance, crossover hop, triple hop, and 6-m timed hop in the order listed. Eight high speed cameras were used to collect simultaneous 3D motion data and Theia 3D (Theia Markerless Inc.) was used to generate 3D body model files. Lower limb joint kinematics were calculated in Visual3D. Correlation (Spearman's ρ) was computed between clinical LSI and symmetry in peak and initial contact (IC) knee flexion angle during propulsion and landing phases of each movement. In the single hop, clinical LSI showed positive correlation with kinematic LSI at peak landing (ρ= 0.39, p=0.011), but no correlation at peak propulsion (ρ= -0.03, p=0.851). In the crossover hop, non-significant correlations were found in both propulsion and landing. In the triple hop, positive correlation was found at peak propulsion (ρ= 0.38, p=0.027), peak landing (ρ= 0.48 - 0.66, p<0.001), and last landing IC (ρ= 0.45, p=0.009). In the timed hop, peak propulsion showed positive correlation (ρ= 0.51, p=0.003). Single hop and triple hop distance symmetry reflected landing biomechanical symmetry better than propulsion symmetry. Poor scores on the hop test battery reflect asymmetrical knee landing biomechanics, emphasizing the importance of continuing to use the hop test battery as part of clinical decision making. 3b.

Understanding social determinants of health (SDOH) that may be risk factors for childhood obesity is important to developing targeted interventions to prevent obesity. Prior studies have examined these risk factors, mostly examining obesity as a static outcome variable. We extracted EHR data from 2012-2019 for a children's health system that includes 2 hospitals and wide network of outpatient clinics spanning 5 East Coast states in the US. Using data-driven and algorithmic clustering, we have identified distinct BMI-percentile classification groups in children from 0 to 7 years of age. We used two separate algorithmic clustering methods to confirm the robustness of the identified clusters. We used multinomial logistic regression to examine the associations between clusters and 27 neighborhood SDOHs and compared positive and negative SDOH characteristics separately. From the cohort of 36,910 children, five BMI-percentile classification groups emerged: always having obesity (n=429; 1.16%), overweight most of the time (n=15,006; 40.65%), increasing BMI-percentile (n=9,060; 24.54%), decreasing BMI-percentile (n=5,058; 13.70%), and always normal weight (n=7,357; 19.89%). Compared to children in the decreasing BMI-percentile and always normal weight groups, children in the other three groups were more likely to live in neighborhoods with higher poverty, unemployment, crowded households, single-parent households, and lower preschool enrollment. Neighborhood-level SDOH factors have significant associations with children's BMI-percentile classification and changes in classification. This highlights the need to develop tailored obesity interventions for different groups to address the barriers faced by communities that can impact the weight and health of children living within them. This study demonstrates the association between longitudinal BMI-percentile patterns and SDOH in early childhood. Five distinct clusters with different BMI-percentile trajectories are found and a strong association between these clusters and SDOH is observed. Our findings highlight the importance of targeted prevention and treatment interventions based on children's SDOH.

Functional interactions between the prefrontal cortex and hippocampus, as revealed by strong oscillatory synchronization in the theta (6–11 Hz) frequency range, correlate with memory-guided decision-making. However, the degree to which this form of long-range synchronization influences memory-guided choice remains unclear. We developed a brain-machine interface that initiated task trials based on the magnitude of prefrontal-hippocampal theta synchronization, then measured choice outcomes. Trials initiated based on strong prefrontal-hippocampal theta synchrony were more likely to be correct compared to control trials on both working memory-dependent and -independent tasks. Prefrontal-thalamic neural interactions increased with prefrontal-hippocampal synchrony and optogenetic activation of the ventral midline thalamus primarily entrained prefrontal theta rhythms, but dynamically modulated synchrony. Together, our results show that prefrontal-hippocampal theta synchronization leads to a higher probability of a correct choice and strengthens prefrontal-thalamic dialogue. Our findings reveal new insights into the neural circuit dynamics underlying memory-guided choices and highlight a promising technique to potentiate cognitive processes or behavior via brain-machine interfacing.

Functional interactions between the prefrontal cortex and hippocampus, as revealed by strong oscillatory synchronization in the theta (6-11 Hz) frequency range, correlate with memory-guided decision-making. However, the degree to which this form of long-range synchronization influences memory-guided choice remains unclear. We developed a brain-machine interface that initiated task trials based on the magnitude of prefrontal-hippocampal theta synchronization, then measured choice outcomes. Trials initiated based on strong prefrontal-hippocampal theta synchrony were more likely to be correct compared to control trials on both working memory-dependent and -independent tasks. Prefrontal-thalamic neural interactions increased with prefrontal-hippocampal synchrony and optogenetic activation of the ventral midline thalamus primarily entrained prefrontal theta rhythms, but dynamically modulated synchrony. Together, our results show that prefrontal-hippocampal theta synchronization leads to a higher probability of a correct choice and strengthens prefrontal-thalamic dialogue. Our findings reveal new insights into the neural circuit dynamics underlying memory-guided choices and highlight a promising technique to potentiate cognitive processes or behavior via brain-machine interfacing.

Wood Ducks (Aix sponsa) are secondary cavity nesters that use natural cavities and artificial nest boxes, the latter of which has been attributed to the recovery of populations across the southeastern US. Continual use of these boxes results in a buildup of bacteria, parasites, and other pathogens. To avoid the accumulation of these deleterious organisms, best management practices include the occasional removal of old nesting material (i.e., wood shavings) and replacement with fresh wood shavings. No studies have been performed on the effects of shaving material on nest box selection, nest success, and bacterial growth. We monitored 142 and 111 nest boxes in Florida and Georgia, USA, respectively, and filled a random sample with aspen or cedar shavings. We then swabbed the surface of 144 and 150 eggs during 2020 and 2021, respectively, to screen for culturable bacteria. We detected no effect of shaving type on nest box selection, nest success, or egg surface bacterial growth. We found 3-8 bacterial colony types (1-123 colony-forming units [CFU]/box) and 1-8 bacterial colony types (3-382 CFU/box) among the Georgia and Florida samples, respectively. We detected no effect from shaving type on Wood Duck reproduction or bacterial growth in the sampled nest boxes. We concluded that both shaving types are suitable nesting materials for box-nesting Wood Duck populations and the continued use of either would be a reasonable decision for managers.

Abstract Experimental research in behavioral economics focuses on consumer behaviors. Similar experimental research on profit-maximizing producers is rare. In three field experiments involving commercial agricultural producers in the United States, we detect evidence of anchoring in competitive auctions for conservation contracts related to nutrient and pest management that were worth, on average, nearly $9,000. In these auctions, the value of the starting cost-share bid was randomized to be either 0% or 100%. When the starting value was 100%, final bids were 46% higher, on average. We find weak evidence that experience with conservation contracts may modestly attenuate the anchoring effect.