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If you are hard-wired to the EMU network on campus, the AD (Active Directory) "Z" drive should automatically map when you log into your computer. If you are wireless or off-campus, you must have the AnyConnect VPN client installed on your computer.

Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate [PI(4)P] on trans-Golgi network (TGN) vesicles were recruited to mitochondria-ER contact sites and could drive mitochondrial division downstream of Drp1. The loss of the small guanosine triphosphatase ADP-ribosylation factor 1 (Arf1) or its effector, phosphatidylinositol 4-kinase III [PI(4)KIII], in different mammalian cell lines prevented PI(4)P generation and led to a hyperfused and branched mitochondrial network marked with extended mitochondrial constriction sites. Thus, recruitment of TGN-PI(4)P-containing vesicles at mitochondria-ER contact sites may trigger final events leading to mitochondrial scission.

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Mitochondria cannot be generated de novo; they must grow, replicate their genome, and divide in order to be inherited by each daughter cell during mitosis. Mitochondrial division is a structural challenge that requires the substantial remodelling of membrane morphology1,2,3. Although division factors differ across organisms, the need for multiple constriction steps and a dynamin-related protein (Drp1, Dnm1 in yeast) has been conserved4,5,6. In mammalian cells, mitochondrial division has been shown to proceed with at least two sequential constriction steps: the endoplasmic reticulum and actin must first collaborate to generate constrictions suitable for Drp1 assembly on the mitochondrial outer membrane; Drp1 then further constricts membranes until mitochondrial fission occurs2,7,8,9. In vitro experiments, however, indicate that Drp1 does not have the dynamic range to complete membrane fission7. In contrast to Drp1, the neuron-specific classical dynamin dynamin-1 (Dyn1) has been shown to assemble on narrower lipid profiles and facilitate spontaneous membrane fission upon GTP hydrolysis10,11. Here we report that the ubiquitously expressed classical dynamin-2 (Dyn2) is a fundamental component of the mitochondrial division machinery. A combination of live-cell and electron microscopy in three different mammalian cell lines reveals that Dyn2 works in concert with Drp1 to orchestrate sequential constriction events that build up to division. Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.

Sk-Mel2 cells endogenously expressing Dyn2-GFP (green) were transfected with mCh-Drp1 (red) and mito-BFP (gray). Time-lapsed images were captured every 5 sec. Line-scan analysis was conducted at each time-point to show the localization of division factors to a constriction that is about to undergo division, as well as, the continuity of the inner mitochondria membrane until membrane fission occurs. This video is represented in Fig. 2a,b. (MOV 26 kb)

COS-7 cells were transfected with Dyn2-mNeon (green), mCh-Drp1 (red) and mito-BFP (gray). Time-lapsed images were captured every 5 sec. Line-scan analysis was conducted at each time-point to show the localization of division factors to a constriction that is about to undergo division, as well as, the continuity of the inner mitochondria membrane until membrane fission occurs. This video is represented in ED Fig. 4a-c. (MOV 30 kb)

PtK1 cells were transfected with Dyn2-mNeon (green), mCh-Drp1 (red) and mito-BFP (gray). Time-lapsed images were captured every 5 sec. Line-scan analysis was conducted at each time-point to show the localization of division factors to a constriction that is about to undergo division, as well as, the continuity of the inner mitochondria membrane until membrane fission occurs. This video is represented in Fig. 2c,d. (MOV 45 kb)

COS-7 cells were transfected with Scrambled siRNA, and plasmids encoding mCh-Drp1 (cyan) and mito-BFP (red). Cells were treated with 10 M BAPTA-AM for 5 minutes followed by live-cell imaging. Time-lapsed images were captured every 5 sec. Line-scan analysis was conducted at each time-point to show the localization of Drp1 to a constriction that is about to undergo division, as well as, the continuity of the inner mitochondria membrane until membrane fission occurs. Drp1 puncta can be observed accumulating at the mitochondrial constriction leading up to division. Upon division, Drp1 puncta splits into two puncta that remain co-localized to the ends of each newly created mitochondrion. This video is represented in Fig. 3d. (MOV 81 kb)

COS-7 cells were transfected with Dyn2 siRNA, and plasmids encoding mCh-Drp1 (cyan) and mito-BFP (red). Cells were treated with 10 M BAPTA-AM for 5 minutes followed by live-cell imaging. Time-lapsed images were captured every 5 sec. Line-scan analysis was conducted at each time-point to show the localization of Drp1 to a constriction that is about to undergo division, as well as, the continuity of the inner mitochondria membrane until membrane fission occurs. The constriction exhibits the dynamics of a division event without the final act of membrane fission. Drp1 puncta separates into two distinct puncta, which coincides with an increase in the width of constriction. The separation of Drp1 puncta and the super-constriction region are transient because the both collapse in a fail division attempt. This video is represented in Fig. 3e. (MOV 114 kb)

New Hampshire does not issue learner's permits; however, a person learning to drive (regardless of the State they reside in) is permitted to drive under certain conditions. Persons whose driving privileges are currently suspended or revoked in NH or any other State, may not practice driving. For the purpose of learning to drive a car, a person who does not possess a valid driver license may practice driving on New Hampshire roadways as long as the below conditions are met:

The adult accompanying the person who is learning to drive must sit in the front seat of the vehicle and must hold a current, valid driver license. The accompanying adult shall be liable for any motor vehicle violation committed by the unlicensed driver. For more information regarding this law, please see RSA 263:25.

Participating in an approved Driver Education program is fundamental to the process of learning to drive a motor vehicle. It is recommended that any person who is learning to drive for the first time take a New Hampshire Approved Driver Education Program. Driver Education is required for anyone under the age of 18, and for non-US citizens temporarily residing in New Hampshire who do not have previous driving experience.

Currently, Delaware has more than 250,000 drivers over the age of 60. With the fastest growing aging population in the United States, Delaware can not afford to ignore the needs of seniors. That is why Delaware is doing more for senior drivers, striving to keep you on the road as long as possible with safety to yourself and others.

Whether you are a senior, family member, or concerned friend, by viewing this website you are taking advantage of an important opportunity to make the roads of Delaware a safer place to drive. Please browse this site for helpful tips and other great resources. From the DMV and our partners, we wish you many years of safe driving!

Exit the freeway at Highway 78 and drive East approximately seven miles. Exit Highway 78 at Melrose Drive and turn right. Proceed approximately 1/4 mile to County Complex Way. Turn right into the parking lot.

Kathy Gould, Ph.D., professor of Cell and Developmental Biology, and colleagues have now identified a direct target of SIN signaling: the formin protein Cdc12, which localizes to the cell middle and is essential for actin assembly in the CR. They report in the Oct. 1 issue of Genes & Development that the SIN protein kinase Sid2 phosphorylates Cdc12. They show that elimination of this modification leads to persistent Cdc12 clustering, which compromises CR assembly and stability leading to defects in cell division.

In order to purchase a parking permit, you must provide a current and valid license plate number for the vehicle that will be displaying the permit. This information will help the parking division serve you better and prevent you from receiving parking tickets if your permit isn't being displayed correctly.

Ever wish you could split your disk drive in two? Maybe you want to encrypt a portion of your drive for sensitive files, or perhaps you want to dual-boot Windows 11 alongside Windows 10. It's actually easy to do, and all the necessary tools are built right into Windows.

This process is called partitioning, and your drive is probably partitioned out of the box. The majority of the drive is occupied by the C: partition, but most PCs also have a small "Recovery" partition that can help repair your system if something goes wrong.

Partitioning your drive seems convenient, but it isn't always the ideal solution to your problem. If you want to encrypt files, for example, it may be easier to create a virtual disk with a program like VeraCrypt. However, by creating a partition, you can use Windows' built-in BitLocker to encrypt an entire partition and avoid using third-party software.

Before partitioning your drive, back up your data. Messing with partitions always carries a small risk that you'll erase the wrong thing and lose some files, so don't start this process before backing up the drive. Windows allows you to create a backup image file, an external recovery drive, or a restore point you can return to if something goes wrong. There are also many third-party backup services we recommend. 17dc91bb1f