Wofford forward Chevez Goodwin, who averaged 11.9 points and 6.2 rebounds last season, is the latest graduate transfer to join USC's basketball team.

L.A. Times Rams beat reporter Gary Klein recalls covering the 2005 BCS national championship game between USC and Texas, which is considered one of the greatest games ever played.

The COVID-19 pandemic has scrambled plans for college football. USC coach Clay Helton said the Trojans would need about four weeks of preparation before the start of fall camp.

Abdul-Malik and Munir McClain, who play football at USC, are living a new normal during the pandemic. It's virtual classrooms and virtual lessons from coaches.

Tayler Katoa was ecstatic when USC coach Clay Helton supported his Mormon mission, but the linebacker always wondered if the Trojans would welcome him back.

Long Beach State center Joshua Morgan will become the fourth basketball player to transfer to USC since the end of the season.

USC's football staff continued its run of recruiting success with the commitment from safety Anthony Beavers Jr., a four-star prospect from Narbonne High.

USC quarterback JT Daniels will enter the transfer portal, the school announced. Daniels started as a freshman in 2018 and missed most of last season with a knee injury.

USC received a commitment Friday from St. John Bosco offensive lineman Maximus Gibbs as the Trojans continued a momentous run on the recruiting trail.

Pasadena Muir four-star defensive back Calen Bullock, who also plays wide receiver, became the third player in four days to commit to the Trojans.

USC offensive tackle Austin Jackson has long envisioned being drafted by the NFL. Even during the coronavirus epidemic, he's ready to hear his name called.

USC wide receiver Michael Pittman Jr. was selected by the Indianapolis Colts with the second pick of the second round in the NFL draft.

USC's lead in all-time NFL draft picks is down to one over Notre Dame after only two Trojans, Michael Pittman Jr. and Austin Jackson, were selected.

Which school has the most No. 1 NFL draft picks of all-time? This is where the rivalry between USC and Notre Dame flares up once again.

USC sophomore guard Elijah Weaver entered the NCAA's transfer portal on Tuesday, saying goodbye to the Trojans in an Instagram post.

USC athletic director Mike Bohn and coaches Clay Helton and Andy Enfield are giving back a combined $1 million in salary to help the school during the coronavirus pandemic.

Johnny Nansen, a victim of USC's recent purge of defensive assistant coaches under Clay Helton, has found a landing spot across town with the Trojans' archrival.

A seven-game win streak and a first-place standing has brought a lot of attention to UCLA's basketball team. But the Bruins' focus on their game against USC on Saturday.

USC tries to stay optimistic in its underdog role at the Pac-12 tournament with the likes of UCLA and Oregon hovering in front of the Trojans.

USC has played pretty good basketball for most of the season, but will Trojans be rewarded with a good showing Saturday against a hot UCLA team?

UCLA's Michaela Onyenwere had 26 points and 15 rebounds and led a fourth-quarter comeback in the Bruins' victory over the Trojans in Las Vegas.

Jonah Mathews hits a three-pointer with one second left to lift USC to a stunning, 54-52 victory over crosstown rival UCLA on Saturday.

'To end it this way, you can't really ask for anything else,' USC's Jonah Mathews said of his game-winning three-pointer against UCLA on Senior Day.

Holocaust survivor Rachmil 'Ralph' Hakman spent three years at Auschwitz-Birkenau as a teen. He then spent decades teaching others about the atrocities.

USC officials said they learned Tuesday that some online Zoom classes had been "disrupted by people who used racist and vile language."

USC admission rates rose significantly for fall 2020 as the coronavirus outbreak deepens uncertainty over students' college plans.

A former admissions official at USC will plead guilty to helping graduate students from China gain acceptance to the school by submitting doctored transcripts and fraudulent recommendation letters.

A lawsuit announced Tuesday seeks refunds for students who, as a result of the coronavirus closures, lost out on in-person instruction, housing, meals and other elements of campus life and were not paid back tuition and fees.

NFL lineman Matt Kalil, who was an All-American at USC, has paid $3.812 million for a gated estate in Pasadena.

Dodge offers two outrageous muscle cars — Hellcat iterations of its Charger and Challenger — that capture the magic of the 1960s horsepower wars.

Indy residents just getting acquainted with Portillo's Chicago-style hotdogs will get to try another new delicacy starting Tuesday: lemon cake

Cycling in Tuscany, Italy

TheAmateur Traveler talks to Mary Jo Manzanares about 4 of her favorite hill towns in southern Tuscany: Contignano , Montalcino, Montepulciano and Pienza. Experience the food, the wine and the slower pace of some of these hill towns.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

Alma L. Burlingame
Apr 1, 2020; 19:571-571
Editorial

Infants born to mothers with obesity have a greater risk for childhood obesity and metabolic diseases; however, the underlying biological mechanisms remain poorly understood. We used a Japanese macaque model to investigate whether maternal obesity combined with a western-style diet (WSD) impairs offspring muscle insulin action. Adult females were fed a control or WSD prior to and during pregnancy through lactation, and offspring subsequently weaned to a control or WSD. Muscle glucose uptake and signaling were measured ex vivo in fetal (n=5-8/group) and juvenile offspring (n=8/group). In vivo signaling was evaluated after an insulin bolus just prior to weaning (n=4-5/group). Maternal WSD reduced insulin-stimulated glucose uptake and impaired insulin signaling at the level of Akt phosphorylation in fetal muscle. In juvenile offspring, insulin-stimulated glucose uptake was similarly reduced by both maternal and post-weaning WSD and corresponded to modest reductions in insulin-stimulated Akt phosphorylation relative to controls. We conclude that maternal WSD leads to a persistent decrease in offspring muscle insulin-stimulated glucose uptake even in the absence of increased offspring adiposity or markers of systemic insulin resistance. Switching offspring to a healthy diet did not reverse the effects of maternal WSD on muscle insulin action suggesting earlier interventions may be warranted.

Mandeep Bajaj
Nov 1, 2005; 54:3148-3153
Metabolism

Christer S. Andreassen
Mar 1, 2006; 55:806-812
Complications

Marlou L. Dirks
Oct 1, 2016; 65:2862-2875
Metabolism

DE Kelley
May 1, 2000; 49:677-683
Articles

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications

D A Pan
Jun 1, 1997; 46:983-988
Original Article

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications

Ralph A DeFronzo
Jun 1, 1988; 37:667-687
Lilly Lecture 1987

David E. Kelley
Oct 1, 2002; 51:2944-2950
Metabolism and Signal Transduction

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine," signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.