The Vancouver Canucks take on the Calgary Flames on Tuesday night.

The Pittsburgh Penguins traded Lars Eller to the Washington Capitals for two draft picks after a blowout loss dropped them to 6-9-2 on the season.

Timo Meier scored the go-ahead goal late in the second period, Jacob Markstrom made 33 saves and the New Jersey Devils snapped Florida’s seven-game winning streak by beating the Panthers 4-1 on Tuesday night.

Washington sent a 2025 fifth-round pick and a 2027 third-round pick to Pittsburgh on Tuesday for Eller.

Nearly 17 million children lack high-speed internet at home that's considered crucial to their ability to participate in remote learning during the pandemic, according to a new study.

Nothing has changed at the top of the second 2024 College Football Playoff rankings.

Nov. 12—PULLMAN — After two rounds of rankings, Washington State is still on the outside looking in on the College Football Playoff. That's the word from the second round of CFP rankings, which placed WSU at No. 18 in Tuesday's reveal show on ESPN, up three spots from last week. The Cougars (8-1) are six spots out of the 12-team field, which is expanding for the first time this season. New ...

We're now eleven weeks into the college football season and that means we have an idea of where Ohio State when it comes to the landscape of the 2024 season. The Buckeyes beat Penn State on the road two weeks ago to boost its resumé and remain right

Caroline Fenton & Jason Fitz react to the second edition of the 2024 College Football Playoff Rankings, discuss Heisman pretenders vs. contenders and preview the biggest matchups of Week 12.

Many schools that have recently opened their doors are already seeing COVID-19 cases among students and staff. Should that shake the confidence of other school leaders who are planning to reopen?

A West Virginia official turns up the heat on financial disclosure for the state’s beleaguered schools, and ruffles feathers in the process.

Governors in several natural resource-dependent states said recently they will have to continue to cut public education funding because prices for oil and coal have not rebounded.

Marie Pino, who taught generations of children in her Navajo community, died at 67. She had lost one of her sons, a school basketball coach, to coronavirus-related illness just weeks before; her husband, an emergency medical coordinator and pastor, died of the illness shortly after she did.

A collection of short news stories from the last week.

Confusion reigns when it comes to finding and reporting data on school-related coronavirus infections. That's a problem for school leaders weighing shutdowns.

Purdue women's basketball suffered its first defeat of the season on Sunday night as No. 6 Notre Dame came into Mackey Arena and handed the Boilermakers a 102-58 loss. The Boilermakers have now lost nine straight games to the Fighting Irish, since taking a 14-5 lead in the series back in 2005. The in-state rivalry was halted, playing just once between 2012 and 2023, but the Fighting Irish resumed their success over the Boilermakers in each of the last two seasons.

Hannah Hidalgo scored 11 of her 28 points in the first 7-plus minutes and No. 6 Notre Dame led by double figures for more than 35 minutes Sunday night as the Fighting Irish beat Purdue 102-58 for their 10th consecutive win over the Boilermakers. Notre Dame (2-0) has a 15-14 lead in its all-time series with Purdue. Olivia Miles added 17 points and Sonia Citron scored 14.

South Carolina a unanimous No. in women's AP Top 25 after 2 wins to open repeat bid; Stanford, Oregon crack rankings.

The Gamecocks earned a hard-fought six-point win over Michigan in Las Vegas to open the season and beat then-No. 9 North Carolina State on Sunday by 14. The two victories made the defending champions a unanimous choice from the 31-member national media panel. In the preseason poll, No. 2 UConn got two first-place votes and No. 3 USC one.

Three stars from Iowa women's basketball's 71-52 victory vs. Virginia Tech.

Per GoBearcats:University of Cincinnati star forward Jillian Hayes has been named Big 12 Player of the Week, the conference announced on Monday. She becomes the first Bearcat to win a weekly Big 12 women's basketball honor in program history.

Nov. 11—Class 3A preseason No. 1 Greensburg opened the season Friday with an 81-23 victory over Jac-Cen-Del. The Lady Pirates opened the scoring with a steal and layup by Mylie Wilkison. After buckets by Clarie Larrison, Mary Harmon, Wilkison and Leah West, the Lady Pirates led 10-0. JCD got on the board with a 3-pointer by Brooklyn Simon. It was all Greensburg from there in the first quarter. ...

Janiah Barker had 18 points and 11 rebounds, Lauren Betts had 17 points and 12 rebounds and the No. 5 UCLA women rolled past Pepperdine 91-54 on Tuesday. The Bruins (3-0) started the game with an 18-0 run. Ornela Muca, who led Pepperdine (1-2) with 20 points, made a 3-pointer to stop the run.

Chance Gray scored 14 of her career-high 31 points in the third quarter and she tied a program-best with nine 3-pointers to help No. 12 Ohio State beat Charlotte 94-53 on Tuesday night. Gray finished 9 of 14 from 3-point range to top her previous best of six makes. Gray scored 11 points in the first half after making all three of her 3-pointers to help Ohio State build a 43-17 lead.

Alexis Markowski scored 22 points, Natalie Potts had a double-double and No. 21 Nebraska cruised to an 84-58 win over Southern on Tuesday night. Potts had 17 points and 12 rebounds, eight on the offensive end, for the Cornhuskers (3-0). Alberte Rimdal added 12 points.

JuJu Watkins had 21 points, nine assists and six steals to help No. 3 Southern California trounce Cal State Northridge 124-39 on Tuesday night. The Trojans (3-0) had six players in double figures, including Kiki Iriafen with 15 points and Kayleigh Heckel with 14 points off the bench. All 13 Trojans who played scored.

Xinying Guo
Oct 23, 2024; 44:e0727242024-e0727242024
Cellular

Elena Neumann
Oct 9, 2024; 44:e0591242024-e0591242024
Systems/Circuits

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

Bradley Voytek
Sep 23, 2015; 35:13257-13265
BehavioralSystemsCognitive

Matthew F. Glasser
Aug 10, 2011; 31:11597-11616
BehavioralSystemsCognitive

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

GABAergic neurons and GABA_A receptors (GABA_ARs) are critical elements of almost all neuronal circuits. Most GABA_ARs of the CNS are heteropentameric ion channels composed of two α, two β, and one subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABA_ARs. Most GABA_AR classifications rely on the heterogeneity of the α subunit (α1–α6) included in the receptor complex. Heterogeneity of the subunits (1–3), which mediate synaptic clustering of GABA_ARs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because 2 subunits greatly outnumber the other subunits in most brain regions. Here, we have investigated a potential role of non-2 GABA_ARs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides 2 subunits, 1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global 2 subunit deletion, which is lethal, spinal cord-specific loss of 2 subunits was well tolerated. GABA_AR clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of 1 subunits that support the synaptic clustering of GABA_ARs in this site. They further suggest that 1 containing GABA_ARs contribute to the spinal control of nociceptive information flow.

Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive. In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA damage–inducing agent generates DNA damage in postmitotic HCs but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA damage–induced cell death and hearing loss.

Perivascular mural cells including vascular smooth cells (VSMCs) and pericytes are integral components of the vascular system. In the central nervous system (CNS), pericytes are also indispensable for the blood–brain barrier (BBB), blood–spinal cord barrier, and blood–retinal barrier and play key roles in maintaining cerebrovascular and neuronal functions. However, the functional specifications of pericytes between CNS and peripheral organs have not been resolved at the genetic and molecular levels. Hence, the generation of reliable CNS pericyte-specific models and genetic tools remains very challenging. Here, we report a new CNS pericyte marker in mice. This putative cation-transporting ATPase 13A5 (Atp13a5) marker was identified through single-cell transcriptomics, based on its specificity to brain pericytes. We further generated a knock-in model with both tdTomato reporter and Cre recombinase. Using this model to trace the distribution of Atp13a5-positive pericytes in mice, we found that the tdTomato reporter reliably labels the CNS pericytes, including the ones in spinal cord and retina but not peripheral organs. Interestingly, brain pericytes are likely shaped by the developing neural environment, as Atp13a5-positive pericytes start to appear around murine embryonic day 15 (E15) and expand along the cerebrovasculature. Thus, Atp13a5 is a specific marker of CNS pericyte lineage, and this Atp13a5-based model is a reliable tool to explore the heterogeneity of pericytes and BBB functions in health and diseases.

The brain's extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows a net-like structure around a subset of neurons, a ring-like structure at the nodes of Ranvier, and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to hyaluronan proteoglycan link protein 1, which links hyaluronan and proteoglycans. Expression or application of the probe in primary rat neuronal cultures enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in mouse brains of either sex reveals detailed ECM architectures around excitatory neurons and developmentally regulated dendritic ECM. Our study uncovers extensive structural features of the brain's ECM, suggesting diverse roles in regulating neuronal plasticity.

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

The precise regulation of Ca²⁺ signals plays a crucial role in the physiological functions of neurons. Here, we investigated the rapid effect of glucocorticoids on Ca²⁺ signals in cultured hippocampal neurons from both female and male rats. In cultured hippocampal neurons, glucocorticoids inhibited the spontaneous somatic Ca²⁺ spikes generated by Kv2.1-organized Ca²⁺ microdomains. Furthermore, glucocorticoids rapidly reduced the cell surface expressions of Kv2.1 and Ca_V1.2 channels in hippocampal neurons. In HEK293 cells transfected with Kv2.1 alone, glucocorticoids significantly reduced the surface expression of Kv2.1 with little effect on K⁺ currents. In HEK293 cells transfected with Ca_V1.2 alone, glucocorticoids inhibited Ca_V1.2 currents but had no effect on the cell surface expression of Ca_V1.2. Notably, in the presence of wild-type Kv2.1, glucocorticoids caused a decrease in the surface expression of Ca_V1.2 channels in HEK293 cells. However, this effect was not observed in the presence of nonclustering Kv2.1S586A mutant channels. Live-cell imaging showed that glucocorticoids rapidly decreased Kv2.1 clusters on the plasma membrane. Correspondingly, Western blot results indicated a significant increase in the cytoplasmic level of Kv2.1, suggesting the endocytosis of Kv2.1 clusters. Glucocorticoids rapidly decreased the intracellular cAMP concentration and the phosphorylation level of PKA in hippocampal neurons. The PKA inhibitor H89 mimicked the effect of glucocorticoids on Kv2.1, while the PKA agonist forskolin abrogated the effect. In conclusion, glucocorticoids rapidly suppress Ca_V1.2-mediated Ca²⁺ signals in hippocampal neurons by promoting the endocytosis of Kv2.1 channel clusters through reducing PKA activity.

A new book reveals striking images from six decades of the beloved Wildlife Photographer of the Year competition

A new book from the Smithsonian’s National Museum of African American History and Culture shows the images and impacts of athletes on and off the playing field

5 December 2014, Rome – At the closure of the FAO Council held today, the [...]

The 2016-17 Programme of Work and Budget will consolidate the existing actions within the Medium Term Plan and the Strategic Framework, emphasizing areas to reflect recent trends and developments, with [...]

Bogotá- Latin America and the Caribbean is at a decisive juncture in its history. Thanks to its advancements in social, economic, and production-based terms, the region is on its way to [...]

Over 100 professional vacancies are in the process of being released and opened for applications. They cover mainly technical areas of work in headquarters and regional offices.

In addition, global calls [...]

Mr Chairman,

I wish to convey, through you, to the Committee on Fisheries, the considered views of the FAO Secretariat on the item on the proposed Fisheries University.  

So far, the [...]