Annals of the New York Academy of Sciences最新文献

Studying the detailed biomechanics of flying animals requires accurate three-dimensional coordinates for key anatomical landmarks. Traditionally, this relies on manually digitizing animal videos, a labor-intensive task that scales poorly with increasing framerates and numbers of cameras. Here, we present a workflow that combines deep learning–powered automatic digitization with filtering and correction of mislabeled points using quality metrics from deep learning and 3D reconstruction. We tested our workflow using a particularly challenging scenario: bat flight. First, we documented four bats flying steadily in a 2 m³ wind tunnel test section. Wing kinematic parameters resulting from manually digitizing bats with markers applied to anatomical landmarks were not significantly different from those resulting from applying our workflow to the same bats without markers for five out of six parameters. Second, we compared coordinates from manual digitization against those yielded via our workflow for bats flying freely in a 344 m³ enclosure. Average distance between coordinates from our workflow and those from manual digitization was less than a millimeter larger than the average human-to-human coordinate distance. The improved efficiency of our workflow has the potential to increase the scalability of studies on animal flight biomechanics.

Halfmask air-purifying respirators are used by millions of workers to reduce inhaling air contaminants, both chemical (e.g., asbestos, styrene) and biological (e.g., SARS-CoV-2, Mycobacterium tuberculosis). In 2006, the federal Occupational Safety and Health Administration (OSHA) promulgated a standard that gave halfmask respirators an assigned protection factor (APF) of 10. This signified that OSHA assumes a fit-tested and trained wearer will experience a 10% maximum total inward leakage of contaminated air into the facepiece. To derive APF = 10, OSHA analyzed data from 16 workplace studies of the efficacy of halfmask respirators worn against particulate contaminants. In this commentary, I contend that, in considering the data, OSHA made several errors that overstated halfmask respirator efficacy. The errors were (i) failing to properly account for within-wearer and between-wearer variability in respirator efficacy; (ii) ignoring the effect of particle deposition in the respiratory tract; (iii) aggregating unbalanced data within and between studies, and effectively double-counting the data in some studies; and (iv) ignoring the effect that particle size exerts in penetrating respirator facepiece leak paths. The net result is that OSHA's APF = 10 can lead to excessive toxicant exposure for many workers.

A considerable proportion of women subjectively perceive a detriment to their cognitive capacity during pregnancy, with decreased memory functions being the most frequently self-reported concerns. However, objective investigation of these perceived cognitive deficits has yielded inconsistent results. This study focused on memory functions during late pregnancy using multiple tasks designed to assess various memory indices, for example, working memory, learning rate, immediate recall, proactive and retroactive interference, delayed recall, retrieval efficiency, visuospatial constructional ability, recognition, and executive function. Additionally, sustained attention and inhibitory control were examined using a combined recognition stop-signal task. Electrophysiological brain activity during this task was recorded using a 128-channel electroencephalographic-event-related potential system. Salivary cortisol levels were assessed both prior to and following the experimental session. In contrast to the widely held belief, results demonstrated that women in late pregnancy did not exhibit a decline in their performance across the various memory tests. In terms of accuracy, there was not a single task in which poorer performance was found for pregnant women. The quality of memory performance was comparable, and in some cases even superior, among women in the pregnancy group. On the stop-signal task, pregnant women exhibited significantly better performance, and their electrophysiological data revealed greater centrally distributed P300 amplitude to “stop” signs, which may signify an enhanced neural efficiency in the domains of inhibitory executive control. Endocrine results revealed that pregnant women exhibited significantly lower levels of salivary cortisol, suggesting an attenuation of hypothalamic−pituitary−adrenocortical axis activity, which may contribute to the optimization of fetal development and growth.

Hippocampal pyramidal neuronal activity has been previously studied using conventional patch clamp in isolated cells and brain slices. We here introduce the loose patch clamping study of voltage-activated currents from in situ pyramidal neurons in murine cornus ammonis 1 hippocampal coronal slices. Depolarizing pulses of 15-ms duration elicited early transient inward, followed by transient and prolonged outward currents in the readily identifiable junctional region between the stratum pyramidalis (SP) and oriens (SO) containing pyramidal cell somas and initial segments. These resembled pyramidal cell currents previously recorded using conventional patch clamp. Shortening the depolarizing pulses to >1–2 ms continued to evoke transient currents; hyperpolarizing pulses to varying voltages evoked decays whose time constants could be shortened to <1 ms, clarifying the speed of clamping in this experimental system. The inward and outward currents had distinct pharmacological characteristics and voltage-dependent inactivation and recovery from inactivation. Comparative recordings from the SP, known to contain pyramidal cell somas, demonstrated similar current properties. Recordings from the SO and stratum radiatum demonstrated smaller inward and outward current magnitudes and reduced transient outward currents, consistent with previous conventional patch clamp results from their different interneuron types. The loose patch clamp method is thus useful for in situ studies of neurons in hippocampal brain slices.

The tight junction protein claudin-7 is essential for tight junction function and intestinal homeostasis. Cldn7 deletion in mice leads to an inflammatory bowel disease-like phenotype exhibiting severe intestinal epithelial damage, weight loss, inflammation, mucosal ulcerations, and epithelial hyperplasia. Claudin-7 has also been shown to be involved in cancer metastasis and invasion. Here, we test our hypothesis that claudin-7 plays an important role in regulating colonic intestinal stem cell function. Conditional knockout of Cldn7 in the colon led to impaired epithelial cell differentiation, hyperproliferative epithelium, a decrease in active stem cells, and dramatically altered gene expression profiles. In 3D colonoid culture, claudin-7–deficient crypts were unable to survive and form spheroids, emphasizing the importance of claudin-7 in stem cell survival. Inhibition of the Hippo pathway or activation of Notch signaling partially rescued the defective stem cell behavior. Concurrent Notch activation and Hippo inhibition resulted in restored colonoid survival, growth, and differentiation to the level comparable to those of wild-type derived crypts. In this study, we highlight the essential role of claudin-7 in regulating Notch and Hippo signaling–dependent colonic stem cell functions, including survival, self-renewal, and differentiation. These new findings may shed light on potential avenues to explore for drug development in colorectal cancer.

Mycobacterium tuberculosis remains the most common infectious killer worldwide despite decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) pandemic will require innovation in drug discovery. In this review, we provide a brief overview of the two main approaches to discovering new TB drugs—phenotypic screens and target-based drug discovery—and outline some of the limitations of each method. We then explore recent advances in genetic tools that aim to overcome some of these limitations. In particular, we highlight a novel metric to prioritize essential targets, termed vulnerability. Stratifying targets based on their vulnerability presents new opportunities for future target-based drug discovery campaigns.

The detrimental effect of math anxiety on math performance is thought to be mediated by executive functions. Previous studies have primarily focused on trait-math anxiety rather than state-math anxiety and have typically examined a single executive function rather than comprehensively evaluating all of them. Here, we used a structural equation modeling approach to concurrently determine the potential mediating roles of different executive functions (i.e., inhibition, switching, and updating) in the relationships between both state- and trait-math anxiety and math performance. A battery of computer-based tasks and questionnaires were administered to 205 university students. Two relevant results emerged. First, confirmatory factor analysis suggests that math anxiety encompassed both trait and state dimensions and, although they share substantial variance, trait-math anxiety predicted math performance over and above state-math anxiety. Second, working memory updating was the only executive function that mediated the relationship between math anxiety and math performance; neither inhibition nor switching played mediating roles. This calls into question whether some general proposals about the relationship between anxiety and executive functions can be extended specifically to math anxiety. We also raise the possibility that working memory updating or general cognitive difficulties might precede individual differences in math anxiety.

Loss of a loved one is a painful event that substantially elevates the risk for physical and mental illness and impaired daily function. Socially monogamous prairie voles are laboratory-amenable rodents that form life-long pair bonds and exhibit distress upon partner separation, mirroring phenotypes seen in humans. These attributes make voles an excellent model for studying the biology of loss. In this review, we highlight parallels between humans and prairie voles, focusing on reward system engagement during pair bonding and loss. As yearning is a unique feature that differentiates loss from other negative mental states, we posit a model in which the homeostatic reward mechanisms that help to maintain bonds are disrupted upon loss, resulting in yearning and other negative impacts. Finally, we synthesize studies in humans and voles that delineate the remodeling of reward systems during loss adaptation. The stalling of these processes likely contributes to prolonged grief disorder, a diagnosis recently added to the Diagnostic and Statistical Manual for Psychiatry.

In 2023, the Keystone Symposia held the first international scientific conference convening research leaders investigating the pathology of post-acute sequelae of COVID-19 (PASC) or Long COVID, a growing and urgent public health priority. In this report, we present insights from the talks and workshops presented during this meeting and highlight key themes regarding what researchers have discovered regarding the underlying biology of PASC and directions toward future treatment. Several themes have emerged in the biology, with inflammation and other immune alterations being the most common focus, potentially related to viral persistence, latent virus reactivation, and/or tissue damage and dysfunction, especially of the endothelium, nervous system, and mitochondria. In order to develop safe and effective treatments for people with PASC, critical next steps should focus on the replication of major findings regarding potential mechanisms, disentangling pathogenic mechanisms from downstream effects, development of cellular and animal models, mechanism-focused randomized, placebo-controlled trials, and closer collaboration between people with lived experience, scientists, and other stakeholders. Ultimately, by learning from other post-infectious syndromes, the knowledge gained may help not only those with PASC/Long COVID, but also those with other post-infectious syndromes.