bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similarities Between Somatosensory Cortical Responses Induced via Natural Touch and Microstimulation in the Ventral Posterior Lateral Thalamus in Macaques
Authors: Francis Joseph Thachil , Rozenboym Anna , von Kraus Lee , Xu Shaohua , Chhatbar Pratik , Semework Mulugeta , Hawley Emerson , Chapin John 
Published: November 2021

ABSTRACTLost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what MiSt will produce a given neural response and possibly a more natural “sensation.” To date, our optimization has been conducted in the rodent model and simulations. Here we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we MiSt in the VPL of macaques with a somatosensory system more like humans. We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL thalamus. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt towards producing a somatosensory neuroprosthesis in humans.
Acoustic and postural displays in a miniature and transparent teleost fish, Danionella dracula
Authors: Tatarsky Rose L. , Guo Zilin , Campbell Sarah C. , Kim Helena , Fang Wenxuan , Perelmuter Jonathan T. , Schuppe Eric R. , Reeve Hudson K. , Bass Andrew H. 
Published: November 2021

ABSTRACTAcoustic communication is widespread across vertebrates, including among fishes. We report robust acoustic displays during aggressive interactions for a laboratory colony of Danionella dracula, a relatively recently discovered miniature and transparent species of teleost fish closely related to zebrafish (Danio rerio). Males produce bursts of pulsatile, click-like sounds and a distinct postural display, extension of a hypertrophied lower jaw, during aggressive but not courtship interactions. Females lack a hypertrophied lower jaw and show no evidence of sound production or jaw extension in such contexts. Novel pairs of size-matched or -mismatched males were combined in resident-intruder assays where sound production and jaw extension could be linked to individuals. Resident males produce significantly more sound pulses and extend their jaw more often than intruders in both dyad contexts, and relatively larger males are significantly more sonic and exhibit more jaw extensions in size-mismatched pairs. The majority of highest sound producers in both contexts also show increased jaw extension during periods of heightened sonic activity. These studies firmly establish D. dracula as a sound-producing species that modulates both acoustic and postural displays during aggressive interactions based on either residency or body size, providing a foundation for further investigating the role of multimodal displays in a new model clade for neurogenomic studies of aggression, courtship, and other social interactions.
Real-time motion monitoring improves functional MRI data quality in infants
Authors: D’Andrea Carolina Badke , Kenley Jeanette K. , Montez David F. , Mirro Amy E. , Miller Ryland L. , Earl Eric A. , Koller Jonathan M. , Sung Sooyeon , Yacoub Essa , Elison Jed T. , Fair Damien A. , Dosenbach Nico U.F. , Rogers Cynthia , Smyser Christopher D. , Greene Deanna J. 
Published: November 2021

AbstractImaging the infant brain with MRI has improved our understanding of early stages of neurodevelopment. However, head motion during MRI acquisition is detrimental to both functional and structural MRI scan quality. Though infants are commonly scanned while asleep, they commonly exhibit motion during scanning, causing data loss. Our group has shown that providing MRI technicians with real-time motion estimates via Framewise Integrated Real-Time MRI Monitoring (FIRMM) software helps obtain high-quality, low motion fMRI data. By estimating head motion in real time and displaying motion metrics to the MR technician during an fMRI scan, FIRMM can improve scanning efficiency. Hence, we compared average framewise displacement (FD), a proxy for head motion, and the amount of usable fMRI data (FD ≤ 0.2mm) in infants scanned with (n = 407) and without FIRMM (n = 295). Using a mixed-effects model, we found that the addition of FIRMM to current state-of-the-art infant scanning protocols significantly increased the amount of usable fMRI data acquired per infant, demonstrating its value for research and clinical infant neuroimaging.
Deep learning methods for designing proteins scaffolding functional sites
Authors: Wang Jue , Lisanza Sidney , Juergens David , Tischer Doug , Anishchenko Ivan , Baek Minkyung , Watson Joseph L. , Chun Jung Ho , Milles Lukas F. , Dauparas Justas , Expòsit Marc , Yang Wei , Saragovi Amijai , Ovchinnikov Sergey , Baker David 
Published: November 2021

AbstractCurrent approaches to de novo design of proteins harboring a desired binding or catalytic motif require pre-specification of an overall fold or secondary structure composition, and hence considerable trial and error can be required to identify protein structures capable of scaffolding an arbitrary functional site. Here we describe two complementary approaches to the general functional site design problem that employ the RosettaFold and AlphaFold neural networks which map input sequences to predicted structures. In the first “constrained hallucination” approach, we carry out gradient descent in sequence space to optimize a loss function which simultaneously rewards recapitulation of the desired functional site and the ideality of the surrounding scaffold, supplemented with problem-specific interaction terms, to design candidate immunogens presenting epitopes recognized by neutralizing antibodies, receptor traps for escape-resistant viral inhibition, metalloproteins and enzymes, and target binding proteins with designed interfaces expanding around known binding motifs. In the second “missing information recovery” approach, we start from the desired functional site and jointly fill in the missing sequence and structure information needed to complete the protein in a single forward pass through an updated RoseTTAFold trained to recover sequence from structure in addition to structure from sequence. We show that the two approaches have considerable synergy, and AlphaFold2 structure prediction calculations suggest that the approaches can accurately generate proteins containing a very wide array of functional sites.
Individual exploration and selective social learning: Balancing exploration-exploitation trade-offs in collective foraging
Authors: Garg Ketika , Kello Christopher T. , Smaldino Paul E. 
Published: November 2021

AbstractSearch requires balancing exploring for more options and exploiting the ones previously found. Individuals foraging in a group face another trade-off: whether to engage in social learning to exploit the solutions found by others or to solitarily search for unexplored solutions. Social learning can better exploit learned information and decrease the costs of finding new resources, but excessive social learning can lead to over-exploitation and too little exploration for new solutions. We study how these two trade-offs interact to influence search efficiency in a model of collective foraging under conditions of varying resource abundance, resource density, and group size. We modeled individual search strategies as Lévy walks, where a power-law exponent (µ) controlled the trade-off between exploitative and explorative movements in individual search. We modulated the trade-off between individual search and social learning using a selectivity parameter that determined how agents responded to social cues in terms of distance and likely opportunity costs. Our results show that social learning is favored in rich and clustered environments, but also that the benefits of exploiting social information are maximized by engaging in high levels of individual exploration. We show that selective use of social information can modulate the disadvantages of excessive social learning, especially in larger groups and when individual exploration is limited. Finally, we found that the optimal combination of individual exploration and social learning gave rise to trajectories withµ ≈2 and provide support for the general optimality of such patterns in search. Our work sheds light on the interplay between individual search and social learning, and has broader implications for collective search and problem-solving.
Epigenetic regulation of translation repression in ferroptosis, and a role of Alternative splicing and tRNA methylation
Authors: Rashad Sherif , Saigusa Daisuke , Zhou Yuan , Zhang Liyin , Tominaga Teiji , Niizuma Kuniyasu 
Published: November 2021

AbstractFerroptosis is a non-apoptotic cell death mechanism characterized by the production of lipid peroxides. Ferroptosis plays important roles in many diseases such as cancer and neurodegenerative diseases. While many effectors in the ferroptosis pathway have been mapped, its epigenetic and epitranscriptional regulatory processes are not yet fully understood. Ferroptosis can be induced via system xCT inhibition (Class I) or GPX4 inhibition (Class II). Previous works have revealed important differences in cellular response to Class I and Class II ferroptosis inducers. Importantly, blocking mRNA transcription or translation appears to protect cells against Class I ferroptosis inducing agents but not Class II. Understanding these subtle differences is important in understanding ferroptosis as well as in developing therapeutics based on ferroptosis for various diseases. In this work, we examined the impact of blocking transcription (via Actinomycin D) or translation (via Cycloheximide) on Erastin (Class I) or RSL3 (Class II) induced ferroptosis. Blocking transcription or translation protected cells against Erastin but was detrimental against RSL3. Cycloheximide led to increased levels of GSH alone or when co-treated with Erastin and the activation of the reverse transsulfuration pathway. RNA sequencing analysis revealed an important and unexplored role of Alternative splicing (AS) in regulating ferroptosis stress response and mRNA translation repression. Our results indicated that translation repression is protective against Erastin but detrimental against RSL3. We tested this theory in Alkbh1 overexpressing glioma cells. Alkbh1 demethylates tRNA and represses translation and is associated with worse outcome in glioma patients. Our results showed that Alkbh1 overexpression protected glioma cells against Erastin but was detrimental against RSL3.
Serum from COVID-19 patients early in the pandemic shows limited evidence of cross-neutralization against variants of concern
Authors: Griffin Amanda J. , O’Donnell Kyle L. , Shifflett Kyle , Lavik John-Paul , Russell Patrick M. , Zimmerman Michelle K. , Relich Ryan F. , Marzi Andrea 
Published: November 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 isolate had detectable but limited neutralizing antibodies against newly circulating SARS-CoV-2 variants of concern. This study highlights the potential of re-infection for recovered COVID-19 patients.
Myocarditis After mRNA-1273 Vaccination: A Population-Based Analysis of 151 Million Vaccine Recipients Worldwide
Authors: Straus Walter , Urdaneta Veronica , Esposito Daina B. , Mansi James A. , Rodriguez Cesar Sanz , Burton Paul , Vega José M. 
Published: November 2021

ABSTRACTBackgroundGrowing evidence indicates a causal relationship between SARS-CoV-2 infection and myocarditis. Post-authorization safety data have also identified myocarditis as a rare safety event following mRNA COVID-19 vaccination, most notably among younger adult males and after dose 2. To further evaluate the potential risk after vaccination, we queried the Moderna global safety database to assess the occurrence of myocarditis/myopericarditis among mRNA-1273 vaccine recipients worldwide since first international Emergency Use Authorization issuance.MethodsReports of myocarditis/myopericarditis entered into the Moderna global safety database from December 18, 2020 to September 30, 2021 were reviewed and classified based on the Brighton Collaboration case definition. The cumulative observed occurrence of myocarditis/myopericarditis was assessed by calculating the reported rate after any known dose of mRNA-1273 according to age and sex. This reporting rate was compared to a population-based incidence rate (US military) to calculate observed-to-expected rate ratios (RR).ResultsThrough September 30, 2021, a total of 1,439 cases of myocarditis/myopericarditis among approximately 151.1 million mRNA-1273 vaccine recipients were reported to the Moderna global safety database. The overall reporting rate among all vaccine recipients was 0.95 cases per 100,000 vaccine recipients, which was lower than the expected rate from the reference population (2.12 cases per 100,000 vaccine recipients; RR [95% CI]: 0.45 [0.42–0.48]). When stratified by sex and age, observed rates were highest for males aged ≤39 years, particularly those aged 18–24 years (7.40 cases per 100,000 vaccine recipients), which was higher than expected (RR [95% CI]: 3.49 [2.88–4.22]). For males and females aged <18 years, the rate ratio for myocarditis was 1.05 (95% CI, 0.52–2.13) and 0.21 (95% CI, 0.04–0.94), respectively. When considering only cases occurring within 7 days after vaccination, the observed rate was highest for males aged 18–24 years after dose 2 (4.9 cases per 100,000 doses administered).ConclusionMyocarditis/myopericarditis accounted for 0.4% of adverse events reported to the Moderna global safety database after mRNA-1273 vaccination; rates were higher than expected in males aged 18–24 years, with most occurring by 7 days after dose 2, but were not higher than expected for the overall population of vaccine recipients and were lower than that observed in individuals infected with SARS-CoV-2.
The primacy of meeting public university students’ essential needs during the COVID-19 pandemic: a new higher education priority
Authors: Manze Meredith , Lattanzio Anna , Larsen Jenna , Keegan Julia , Freudenberg Nick , Jones Heidi E. 
Published: November 2021

AbstractObjectivesWe investigated the holistic experiences of university students during the pandemic.Participants38 students in a public university system in New York City (NYC) purposively selected from neighborhoods highly affected by the pandemic based on level of self-reported impactMethodsWe conducted virtual in-depth interviews from May to August 2021 and analyzed data using thematic coding and constant comparison techniques informed by grounded theory.ResultsFinancial and social support systems, such as governmental and school resources, were critical to addressing essential needs and allowing students to persist. For those whose essential needs were met, faculty members’ flexibility and students’ experience with online learning were central to their academic success.ConclusionsInstitutions of higher education should strengthen financial and social support systems to meet students’ essential needs. Academic policies to bolster online pedagogy and faculty’s flexibility can facilitate student retention and completion.
Abolishing the prelamin A ZMPSTE24 cleavage site leads to progeroid phenotypes with near-normal longevity in mice
Authors: Wang Yuexia , Shiladardi Khurts , Hsu Trunee , Odinammadu Kamsi O. , Maruyama Takamitsu , Wu Wei , Lin Chyuan-Sheng , Damoci Christopher B. , Spear Eric D. , Shin Ji-Yeon , Hsu Wei , Michaelis Susan , Worman Howard J. 
Published: November 2021

AbstractPrelamin A is a farnesylated precursor of lamin A, a nuclear lamina protein. Accumulation of the farnesylated prelamin A variant progerin, with an internal deletion including its processing site, causes Hutchinson-Gilford progeria syndrome. Loss of function mutations inZMPSTE24, which encodes the prelamin A processing enzyme, lead to accumulation of full-length farnesylated prelamin A and cause related progeroid disorders. Some data suggest that prelamin A also accumulates with physiological aging.Zmpste24-/-mice die young, at ~20 weeks. Because ZMPSTE24 has functions in addition to prelamin A processing, we generated a mouse model to examine effects solely due to the presence of permanently farnesylated prelamin A. These mice have an L648R amino acid substitution in prelamin A that blocks ZMPSTE24-catalyzed processing to lamin A. TheLmnaL648R/L648Rmice express only prelamin and no mature protein. Notably, nearly all survive to 65-70 weeks, with approximately 40% of male and 75% of femaleLmnaL648R/L648Rmice having near-normal lifespans of 90 weeks (almost 2 years). Starting at ~10 weeks of age, LmnaL648R/L648Rmice of both sexes have lower body masses and body fat than controls. By ~20-30 weeks of age, they exhibit detectable cranial, mandibular and dental defects similar to those observed inZmpste24-/-mice, and have decreased vertebral bone density compared to age- and sex-matched controls. Cultured embryonic fibroblasts fromLmnaL648R/L648Rmice have aberrant nuclear morphology that is reversible by treatment with a protein farnesyltransferase inhibitor. These novel mice provide a robust model to study the effects of farnesylated prelamin A during physiological aging.
Regulating peroxisome-ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β
Authors: Kors Suzan , Hacker Christian , Bolton Chloe , Maier Renate , Reimann Lena , Kitchener Emily J.A. , Warscheid Bettina , Costello Joseph L. , Schrader Michael 
Published: November 2021

AbstractPeroxisomes and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism. They form membrane contacts through interaction of the peroxisomal membrane protein ACBD5 [acyl-coenzyme A-binding domain protein 5] and the ER-resident protein VAPB [vesicle-associated membrane protein-associated protein B]. ACBD5 binds to the major sperm protein domain of VAPB via its FFAT-like [two phenylalanines (FF) in an acidic tract] motif. However, molecular mechanisms, which regulate formation of these membrane contact sites, are unknown. Here, we reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation. We show that ACBD5-VAPB binding is phosphatase-sensitive and identify phosphorylation sites in the flanking regions and core of the FFAT-like motif, which alter interaction with VAPB and thus, peroxisome-ER contact sites differently. Moreover, we demonstrate that GSK3β [glycogen synthase kinase-3 beta] regulates this interaction. Our findings reveal for the first time a molecular mechanism for the regulation of peroxisome-ER contacts in mammalian cells and expand the current model of FFAT motifs and VAP interaction.SUMMARYKors et al. reveal that peroxisome-ER associations via the ACBD5-VAPB tether are regulated by phosphorylation and GSK3β in mammalian cells. Phosphorylation sites in the FFAT-like motif of ACBD5 affect the binding to VAPB and thus, peroxisome-ER contact sites, differently.
Preclinical studies for plant-based oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice with transgenic tobacco seeds expressing human GAA (tobrhGAA)
Authors: Martiniuk Frank , Mack Adra , Martiniuk Justin , Miller Shoreh , Voronin Gregory O. , Reimer David , Rossi Nancy , Bird Leslie Sheppard , Saleh Sussan , Gupta Ruby , Nigro Mariel , Meinke Peter , Schoser Benedikt , Wu Feng , Kambitsis Angelo , Arvanitopoulos John , Arvanitopoulos Elena , Tchou-Wong Kam-Meng 
Published: November 2021

ABSTRACTGenetic deficiency of acid α-glucosidase (GAA) results in glycogen storage disease type II (GSDII) or Pompe disease (PD) encompassing at least four clinical subtypes of varying severity (infantile; childhood, juvenile and late onset). Our objective is to develop an innovative and affordable approach for enzyme replacement therapy (ERT) via oral administration (Oral-ERT) to maintain a sustained, therapeutic level of enzyme on a daily basis to improve efficacy of treatment and quality of life for people living with Pompe disease. A consensus at a 2019 US Acid Maltase Deficiency (AMDA) conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment of Pompe disease. Tobacco seeds contain the metabolic machinery that is more compatible with mammalian glycosylation-phosphorylation and processing. Previously, we have shown that a lysate from transgenic tobacco seeds expressing human GAA (tobrhGAA) was enzymatically active and can correct enzyme deficiency in cultured PD cells and in adult lymphocytes of Pompe patients and in vivo in disease-relevant tissues in GAA knockout (KO) mice when administered IP.We have extended these pre-clinical studies in PD knockout (KO) mice with ground tobrhGAA seeds that supports proof-of-concept for Oral-ERT for future clinical trials. Briefly in GAA KO mice, Oral-ERT with ground tobrhGAA seeds showed significant reversal of fore-limb and hind-limb muscle weakness, increased motor coordination/balance/strength and mobility, improved spontaneous learning, increased GAA baseline activity in tissues, reduced glycogen in tissues and negible serum titers to GAA. Pharmacokinetics showed maximum serum GAA concentration (Cs) at 8-10 hr and peak urine excretion at 10-12 hr. The tobrhGAA was taken up in PD fibroblast, lymphoid and myoblast cells. Enzyme kinetics compared favorably or superior to placental hGAA, plus alglucosidase alfa or other rhGAAs for Km, Vmax, pH optima, thermal heat stability and IC50 for inhibitors. The tobrhGAA in seeds was extremely stable stored for 15 years at room temperature. NGS-genome sequencing of the tobrhGAA and wild-type plants and RNA expression profiles was performed and will be posted on our website. Thus, Oral-ERT with ground tobrhGAA seeds is an innovative approach that overcomes some of the challenges of alglucosidase alfa-ERT and provides a more effective, safe and significantly less expensive treatment.