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UCSF JOURNAL CLUB

 

Thu
30
Apr

UCSF Journal Club

Taylor LaFlam
Science Editor

STRUCTURAL BIOLOGY: Structure of the TRPA1 ion channel suggests regulatory mechanisms. Paulsen, C.E., et al. (Julius, D.). Nature. 2015. Epub ahead of print. 

Various ion channels in sensory neurons play an important role in reacting to noxious chemicals and other painful stimuli. In addition, they can have side benefits; for example, the receptor TRPA1 lets us appreciate the bite of wasabi in our Japanese food.

However, TRPA1 also plays an important role in some neurogenic inflammation, and better understanding it could aid development of new treatments. Here, the Julius group has determined the structure of TRPA1 using single-particle electron cryo-microscopy, an alternative to traditional X-ray crystallography. 

Wed
15
Apr

UCSF Journal Club

Taylor LaFlam
Science Editor

DEVELOPMENTAL BIOLOGY: Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription. Koh, F.M., et al. (Ramalho-Santos, M.). PNAS. 2015. Epub ahead of print.

The long-lasting hematopoietic stem cells that occupy the bone marrow and proliferate and differentiate into new blood cells throughout life arise from endothelium in the embryo. Much is unknown about how this endothelial-to-hematopoietic transition is controlled.

Here the Ramalho-Santos lab reports that the chromatin-remodeling protein Chd1 is essential for this process. Deletion of the Chd1 gene in endothelium leads to anemia and death of the mouse embryo fifteen days after conception. Interestingly, when the gene is deleted hematopoietic cells, the mice survive.

Thu
02
Apr

UCSF Journal Club

By Taylor LaFlam
Science Editor

CARDIOLOGY & CELL BIOLOGY: Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency. Theodoris, C.V., et al. (Srivastava, D.). Cell. 2015. 160(6):1072-1086

Sometimes both copies of a given gene can be severely mutated, and the body can compensate just fine. At other times, however, even having one perfectly good copy isn’t enough.

Severe mutations in just one allele of NOTCH1 cause abnormal aortic valve development, leading to valve calcification and damage. Here, Theodoris and colleagues report mechanisms by which decreased NOTCH1 dosage leads to disrupted cell biology.

Wed
18
Mar

UCSF Journal Club

By Taylor LaFlam
Science Editor

CELL BIOLOGY: Early telomerase inactivation accelerates aging independently of telomere length. Xie, Z., et al. (Blackburn, E.H.) Cell. 2015. 160(5):928-939.

Telomeres, repetitive DNA sequences at the end of chromosomes, are essential for DNA protection. Loss of the telomerase enzyme leads to gradual shortening of telomeres—after each cell division—leading, eventually, to a DNA damage response and loss of the ability to keep proliferating.

Previous research has only described the consequences of telomerase inactivity after many cell divisions. This paper from the Blackburn lab, however, presents evidence that deletion of telomerase leads to negative effects long before telomeres substantially shorten.

Thu
05
Mar
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UCSF Journal Club

By Taylor LaFlam
Science Editor

 

NEUROSCIENCE: RIM-binding protein links synaptic homeostasis to the stabilization and replenishment of high release probability vesicles. Müller, M., Genç, Ö., and Davis, G.W. Neuron. 2015. Epub ahead of print

Control of muscles requires many levels of careful regulation, including at the synapse between the muscle-innervating nerve and the muscle fiber. The nerve ending responds to changes in sensitivity of the muscle by tuning its own release of neurotransmitters.

Previous research has found the mechanism for this self-tuning involves both adjustments in calcium influx and the size of the readily releasable pool of vesicles. Whether, and how, these two processes were co-regulated was unclear, but in this paper the authors find a unifying element.

Wed
18
Feb
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UCSF Journal Club: Recent research

By Taylor LaFlam
Science Editor

MICROBIOLOGY: Use of 16S rRNA gene for identification of a broad range of clinically relevant bacterial pathogens. Srinivasan, R., et al. (Lynch, S.V.). PLoS One. 2015. 10(2):e0117617.

Definitive diagnosis of infectious diseases frequently rests on growing a culture of the offending organism—this can be a time-consuming process and not all bacteria can be successfully cultured.

Mon
02
Feb
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UCSF Journal Club: Recent research by UCSF scientists

By Taylor LaFlam
Science Editor

IMMUNOLOGY: A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity. Duong, B.H., et al. (Ma, A.). Immunity. 2015. 42(1):55-67.

The production of certain inflammatory molecules, including interleukin-1β (IL-1β), requires the activity of large protein complexes called inflammasomes. Aberrant activation of inflammasomes has been linked to several diseases in which the immune system acts against the body.

Here, Duong and colleagues add to the field’s growing understanding of how these inflammasomes are normally controlled. They show that the protein A20, already well known in immunology for its role as a negative regulator of an important signaling pathway, is required for normal regulation of a particular inflammasome.

Tue
20
Jan
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UCSF Journal Club: Recent research by UCSF scientists

By Taylor LaFlam
Science Editor

NEUROSCIENCE: An estrogen-responsive module in the ventromedial hypothalamus selectively drives sex-specific activity in females. Correa, S.M., et al. (Ingraham, H.A.). Cell Rep. 2015. 10(1):62-74

Efforts to identify intrinsic, biological causes for differences in the behaviors typical of men and women (or boys and girls) must also carefully consider the role of culture. In mice, you can feel a lot safer about just pinning it on the biology.

Previous research has found that estrogen-receptor-alpha neurons in part of the ventromedial hypothalamus in the brain are essential for multiple sex-specific behaviors. Here, the authors found evidence that different subsets of these neurons control different behaviors.

Tue
06
Jan
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UCSF Journal Club: Recent research by UCSF scientists

By Taylor LaFlam
Science Editor

PHYSIOLOGY: Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Vaughan, A.E., et al. (Chapman, H.A.). Nature. 2014 Dec 24. Epub ahead of print.

In some organs, tissue growth and regrowth is driven by proliferation of an already mature cell; in other settings, it is driven by proliferation of progenitor cells, followed by maturation. Current models of lung epithelial regeneration argue for the first case, in which expanding mature cells support recovery.

However, in this paper, the Chapman lab identified a new, rare progenitor cell present in the normal lung. They found that these cells, which are quiescent under normal conditions, allow epithelial recovery in mice after lung injury from influenza infection or the chemical bleomycin.

Sun
07
Dec
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UCSF Journal Club: Recent research by UCSF scientists

By Taylor LaFlam
Science Editor

NEUROSCIENCE: Radial glia required PDGFD-PDGFRβ signaling in human but not mouse neocortex. Lui, J.H., et al. (Oldham). Nature. 2014. 515(7526):264-268.

How did humans evolve their particular mental abilities? What genetic changes make us distinct from other animals? A recent paper by Lui and colleagues provides a small step toward the answers to those questions.

Humans have a relatively much larger neocortex than mice. This larger neocortex has been hypothesized to be due to more proliferation by radial glia. Here, the authors compared the gene expression of radial glia in human and mouse and found production of the growth factor PDGFD only in human.