Inwardly rectifying K+ (Kir) channels allow K+ to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are ...

Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles

Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology.

Pathophysiology of Migraine: A Disorder of Sensory Processing

Proteins. Structures and molecular properties, T.E. Creighton. W. H. Freeman and Company, New York (1984), 515, $36.95

Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective.

We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia). By analysis of linkage we localize the putative causative gene to a 2.5-Mb segment of chromosome 1q23.2-23.3. Direct DNA sequencing of KCNJ10, which encodes an inwardly rectifying K(+) channel, identifies previously unidentified missense or nonsense mutations on both alleles in all affected subjects. These mutations alter highly conserved amino acids and are absent among control chromosomes. Many of these mutations have been shown to cause loss of function in related K(+) channels. These findings demonstrate that loss-of-function mutations in KCNJ10 cause this syndrome, which we name SeSAME. KCNJ10 is expressed in glia in the brain and spinal cord, where it is believed to take up K(+) released by neuronal repolarization, in cochlea, where it is involved in the generation of endolymph, and on the basolateral membrane in the distal nephron. We propose that KCNJ10 is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for K(+) recycling across the basolateral membrane to enable normal activity of the Na(+)-K(+)-ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for KCNJ10 show a related phenotype with seizures, ataxia, and hearing loss, further supporting KCNJ10's role in this syndrome. These findings define a unique human syndrome, and establish the essential role of basolateral K(+) channels in renal electrolyte homeostasis.

https://www.pnas.org/content/pnas/106/14/5842.full.pdf

Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10

The recent global COVID-19 pandemic has had profound economic and social impacts on the world. It has highlighted an urgent need to strengthen existing international biosecurity governance mechanisms to prevent the misuse and malicious abuse of life science research and maintain international biological arms control norms. Biologists are at the front line of biotechnology development and are key to maintaining biosecurity awareness and moral self-discipline. As an important first step, biologists need to actively participate in the formulation and implementation of relevant biosecurity policies and measures to ensure their effectiveness and sustainability. Furthermore, efforts should be made to advocate for and promote the establishment of an ethical code of conduct for biologists to share safety responsibilities for global biosecurity. To maximize the impact of this ethical code of conduct, an effective approach to implementing codes of conduct for biologists at both national and international levels should be established under the framework of the Biological and Toxin Weapons Convention (BTWC).

Building and implementing a multi-level system of ethical code for biologists under the Biological and Toxin Weapons Convention (BTWC) of the United Nations

/pdf/act-now-to-close-chemical-weapons-loophole-47eha9ngz5.pdf

Act now to close chemical-weapons loophole.

Preserving the norm against chemical weapons: A civil society initiative for the 2018 4th review conference of the chemical weapons convention

In this report, we identify some of the key technical and political challenges currently facing the broader Chemical and Biological Weapon (CBW) regime- with a particular emphasis on major forthcoming diplomatic meetings. Most significantly the Ninth Review Conference of the Biological and Toxins Weapons Convention (1972) (BTWC) which will take place in 2022 and preparations for the Fifth Review Conference of the Chemical Weapons Convention (1993) (CWC), expected in 2023. This report is an output of an ongoing project, designed to stimulate thinking and discussion about these issues, within relevant stakeholder communities. The report provides an introduction to this issue area for the general reader before surveying key issues and developing a series of practical policy suggestions for further consideration.

Lijun Shang

Papers

Building and implementing a multi-level system of ethical code for biologists under the Biological and Toxin Weapons Convention (BTWC) of the United Nations

Act now to close chemical-weapons loophole.

Preserving the norm against chemical weapons: A civil society initiative for the 2018 4th review conference of the chemical weapons convention

Meeting the Challenges of Chemical and Biological Weapons: Strengthening the Chemical and Biological Disarmament and Non-proliferation Regimes

Melanocortin receptor-4 mediates the anorectic effect induced by the nucleus tractus solitarius injection of glucagon-like Peptide-2 in fasted rats.