Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans

All terrestrial animals must find a proper level of moisture to ensure their health and survival. The cellular-molecular basis for sensing humidity is unknown in most animals, however. We used the model nematode Caenorhabditis elegans to uncover a mechanism for sensing humidity. We found that whereas C. elegans showed no obvious preference for humidity levels under standard culture conditions, worms displayed a strong preference after pairing starvation with different humidity levels, orienting to gradients as shallow as 0.03% relative humidity per millimeter. Cell-specific ablation and rescue experiments demonstrate that orientation to humidity in C. elegans requires the obligatory combination of distinct mechanosensitive and thermosensitive pathways. The mechanosensitive pathway requires a conserved DEG/ENaC/ASIC mechanoreceptor complex in the FLP neuron pair. Because humidity levels influence the hydration of the worm’s cuticle, our results suggest that FLP may convey humidity information by reporting the degree that subcuticular dendritic sensory branches of FLP neurons are stretched by hydration. The thermosensitive pathway requires cGMP-gated channels in the AFD neuron pair. Because humidity levels affect evaporative cooling, AFD may convey humidity information by reporting thermal flux. Thus, humidity sensation arises as a metamodality in C. elegans that requires the integration of parallel mechanosensory and thermosensory pathways. This hygrosensation strategy, first proposed by Thunberg more than 100 y ago, may be conserved because the underlying pathways have cellular and molecular equivalents across a wide range of species, including insects and humans.Moisture is essential for life. As such, many animals have adapted different behavioral mechanisms to migrate toward their preferred moisture level (hygrotaxis) (1–6). For instance, Drosophila avoid high humidity that impedes flight, whereas green frogs orient toward high humidity to maintain hydration (5, 6). Animals also sense moisture levels to determine important information about their environment; for example, moths detect humidity levels around flowers to deduce which ones might be damaged and contain less nectar (7). These behaviors are often critical to keep an animal within its niche and regulate essential processes such as growth and reproduction. Thus, it is surprising that the molecular basis for how different humidity levels are detected and encoded by the nervous system (hygrosensation) remains unknown in most animals.The search for humidity receptors has achieved the most progress in insects. For instance, distinct sets of hygrosensitive neurons have been found in dome-shaped organs on the antenna of the giant cockroach (8). One set activates with moist air, and the other set responds to dry air. Similar moist and dry receptive neurons have been detected in the branched arista subsegment of the antennae in adult Drosophila (9). Removal of the arista or deletion of any one of three TRP channels expressed in the arista prevents hygrotaxis (5, 9). These TRP channels represent tantalizing candidates for moisture receptors because different TRP channels were required for activity of moist or dry neuronal responses (9). Whether these TRP channels contribute to hygrosensation in other animals remains to be seen, however.Humidity also can be detected by animals that lack branched organs or hair that changes shape with hydration. In 1905, Thunberg (10) proposed that humidity may be perceived in humans as the synthesis of mechanical distension associated with changes in skin hydration, along with temperature signals from the rate of evaporative cooling. This old idea might apply to other animals as well; for instance, the hygrosensitive organs in cockroach and Drosophila also house thermosensitive neurons (8, 11). Whether paired thermosensitive neurons are required for hygrosensation in insects or, for that matter, whether any animal (including humans) senses humidity via this mechanism, remains unknown.To gain information about the neuromolecular basis for hygrosensation, we studied how the free-living nematode Caenorhabditis elegans responds to humidity gradients. This model has been used to successfully elucidate neuronal mechanisms and molecules critical for diverse sensory pathways (12–14). We expected C. elegans to be sensitive to humidity because its small volume (∼3.8 × 10⁶ μm³) and hydrostatic skeleton make it vulnerable to desiccation and overhydration, which are often lethal to this tiny (∼1 mm) worm (15). Although C. elegans does not feature an arista-like appendage, its completely described nervous system of 302 neurons conveniently limits the search for candidate hygroreceptive neurons. Here we report that C. elegans appears to use a strategy for hygrosensation first predicted by Thunberg (10) that combines dual mechanosensory and thermosensory pathways.     

Clinical bond failure rates of adhesive precoated self-ligating brackets using a self-etching primer

Objective:To comparatively assess the failure rate of adhesive precoated (APC) self-ligating metal brackets bonded with two different enamel surface preparation techniques: self-etching primer (SEP) and conventional two-step etch and primer method (CM).Materials and Methods:Fifty-seven patients with complete permanent dentition were included in this study. A total of 1140 APC self-ligating brackets (3M Unitek, Monrovia, Calif) were bonded using a split-mouth design. For each patient, SEP (Transbond Plus SEP, 3M Unitek) and CM (37% phosphoric acid) were used in alternate quadrants. All brackets were bonded by the same investigator after pumicing and rinsing of all of the teeth. The number, site, and date of first-time bracket failures were monitored throughout orthodontic treatment (mean, 22 months). The survival rates of the brackets were estimated by Kaplan-Meier and log-rank tests (P < .05). The adhesive remnant index was used to determine the bond failure interface.Results:The bond failure rates were 2.97% and 2.18% for the CM and SEP, respectively. No statistically significant difference in failure rates was found between the groups. The bond failure sites were predominantly at the enamel-adhesive interface in both groups.Conclusion:This long-term in vivo study showed that the combined use of SEP and the APC bracket system can be used effectively for bonding brackets after pumicing the enamel surfaces in clinical orthodontics.     

Has Omicron Changed the Evolution of the Pandemic?

BackgroundVariants of the SARS-CoV-2 virus carry differential risks to public health. The Omicron (B.1.1.529) variant, first identified in Botswana on November 11, 2021, has spread globally faster than any previous variant of concern. Understanding the transmissibility of Omicron is vital in the development of public health policy.ObjectiveThe aim of this study is to compare SARS-CoV-2 outbreaks driven by Omicron to those driven by prior variants of concern in terms of both the speed and magnitude of an outbreak.MethodsWe analyzed trends in outbreaks by variant of concern with validated surveillance metrics in several southern African countries. The region offers an ideal setting for a natural experiment given that most outbreaks thus far have been driven primarily by a single variant at a time. With a daily longitudinal data set of new infections, total vaccinations, and cumulative infections in countries in sub-Saharan Africa, we estimated how the emergence of Omicron has altered the trajectory of SARS-CoV-2 outbreaks. We used the Arellano-Bond method to estimate regression coefficients from a dynamic panel model, in which new infections are a function of infections yesterday and last week. We controlled for vaccinations and prior infections in the population. To test whether Omicron has changed the average trajectory of a SARS-CoV-2 outbreak, we included an interaction between an indicator variable for the emergence of Omicron and lagged infections.ResultsThe observed Omicron outbreaks in this study reach the outbreak threshold within 5-10 days after first detection, whereas other variants of concern have taken at least 14 days and up to as many as 35 days. The Omicron outbreaks also reach peak rates of new cases that are roughly 1.5-2 times those of prior variants of concern. Dynamic panel regression estimates confirm Omicron has created a statistically significant shift in viral spread.ConclusionsThe transmissibility of Omicron is markedly higher than prior variants of concern. At the population level, the Omicron outbreaks occurred more quickly and with larger magnitude, despite substantial increases in vaccinations and prior infections, which should have otherwise reduced susceptibility to new infections. Unless public health policies are substantially altered, Omicron outbreaks in other countries are likely to occur with little warning.