CaMKII binds both substrates and activators at the active site.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a signaling protein required for long-term memory. When activated by Ca2+/CaM, it sustains activity even after the Ca2+ dissipates. In addition to the well-known autophosphorylation-mediated mechanism, interaction with specific binding partners also persistently activates CaMKII. A long-standing model invokes two distinct S and T sites. If an interactor binds at the T-site, then it will preclude autoinhibition and allow substrates to be phosphorylated at the S site. Here, we specifically test this model with X-ray crystallography, molecular dynamics simulations, and biochemistry. Our data are inconsistent with this model. Co-crystal structures of four different activators or substrates show that they all bind to a single continuous site across the kinase domain. We propose a mechanistic model where persistent CaMKII activity is facilitated by high-affinity binding partners that kinetically compete with autoinhibition by the regulatory segment to allow substrate phosphorylation.

Weddell seals produce ultrasonic vocalizations.

Seals (phocids) are generally not thought to produce vocalizations having ultrasonic fundamental frequencies (≥20 kHz), although previous studies could have been biased by sampling limitations. This study characterizes common, yet, previously undescribed, ultrasonic Weddell seal (Leptonychotes weddellii) vocalizations. The vocalizations were identified in more than one year (2017-2018) of broadband acoustic data obtained by a continuously recording underwater observatory in McMurdo Sound, Antarctica. Nine recurrent call types were identified that were composed of single or multiple vocal elements whose fundamental frequencies spanned the ultrasonic range to nearly 50 kHz. Eleven vocal elements had ultrasonic center frequencies (≥20 kHz), including chirps, whistles, and trills, with two elements at >30 kHz. Six elements had fundamental frequencies always >21 kHz. The fundamental frequency of one repetitive U-shaped whistle element reached 44.2 kHz and descending chirps (≥3.6 ms duration) commenced at ≤49.8 kHz. The source amplitude of one fully ultrasonic chirp element (29.5 kHz center frequency) was 137 dB re 1 µPa-m. Harmonics of some vocalizations exceeded 200 kHz. Ultrasonic vocalizations occurred throughout the year with the usage of repetitive ultrasonic chirp-based calls appearing to dominate in winter darkness. The functional significance of these high-frequency vocalizations is unknown.

School Closure Decisions Made by Local Health Department Officials During the 2009 H1N1 Influenza Outbreak.

OBJECTIVES: The goal of this study was to gain insights into the decision-making processes used by California public health officials during real-time crises. The decision-making processes used by California public health officials during the 2009 H1N1 influenza pandemic were examined by a survey research team from the University of California Berkeley. METHODS: The survey was administered to local public health officials in California. Guidelines published by the Centers for Disease Control and Prevention had recommended school closure, and local public health officials had to decide whether to follow these recommendations. Chi-squared tests were used to make comparisons in the descriptive statistics. RESULTS: The response rate from local public health departments was 79%. A total of 73% of respondents were involved in the decision-making process. Respondents stated whether they used or did not use 15 ethical, logistical, and political preselected criteria. They expressed interest in receiving checklists and additional training in decision-making. CONCLUSIONS: Public health decision-makers do not appear to have a standard process for crisis decision-making and would benefit from having an organized decision-making model. The survey showed that ethical, logistical, and political criteria were considered but were not prioritized in any meaningful way. A new decision-making tool kit for public health decision-makers plus implementation training is warranted.