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The April 25, 2015 Mw 7.9 Gorkha earthquake in Nepal was characterized by a peak slip of several meters and persisting aftershocks. We report here that, in addition, a dense seismic swarm initiated abruptly in August 2017 at the western edge of the afterslip region, below the high Himalchuli-Manaslu range culminating at 8156 m, a region seismically inactive during the past 35 years. Over 6500 events were recorded by the Nepal National Seismological Network with local magnitude ranging between 1.8 and 3.7 until November 2017. This swarm was reactivated between April and July 2018, with about 10 times less events than in 2017, and in 2019 with only sporadic events. The relocation of swarm earthquakes using proximal temporary stations ascertains a shallow depth of hypocenters between the surface and 20 km depth in the High Himalayan Crystalline slab. This swarm reveals an intriguing localized interplay between orogenic collapse and stress adjustments, involving possibly CO2-rich fluid migration, more likely post-seismic slip and seasonal enhancements.

Enhancers drive the gene expression patterns required for virtually every process in metazoans. We propose that enhancer length and transcription factor (TF) binding site composition—the number and identity of TF binding sites—reflect the complexity of the enhancer's regulatory task. In development, we define regulatory task complexity as the number of fates specified in a set of cells at once. We hypothesize that enhancers with more complex regulatory tasks will be longer, with more, but less specific, TF binding sites. Larger numbers of binding sites can be arranged in more ways, allowing enhancers to drive many distinct expression patterns, and therefore cell fates, using a finite number of TF inputs. We compare ~100 enhancers patterning the more complex anterior-posterior (AP) axis and the simpler dorsal-ventral (DV) axis in Drosophila and find that the AP enhancers are longer with more, but less specific binding sites than the (DV) enhancers. Using a set of ~3,500 enhancers, we find enhancer length and TF binding site number again increase with increasing regulatory task complexity. Therefore, to be broadly applicable, computational tools to study enhancers must account for differences in regulatory task.

The blood-brain barrier (BBB) is located at the interface between the vascular system and the brain parenchyma, and is responsible for communication with systemic circulation and peripheral tissues. During life, the BBB can be subjected to a wide range of perturbations or stresses that may be endogenous or exogenous, pathological or therapeutic, or intended or unintended. The risk factors for many diseases of the brain are multifactorial and involve perturbations that may occur simultaneously (e.g., two-hit model for Alzheimer’s disease) and result in different outcomes. Therefore, it is important to understand the influence of individual perturbations on BBB function in isolation. Here we review the effects of eight perturbations: mechanical forces, temperature, electromagnetic radiation, hypoxia, endogenous factors, exogenous factors, chemical factors, and pathogens. While some perturbations may result in acute or chronic BBB disruption, many are also exploited for diagnostic or therapeutic purposes. The resultant outcome on BBB function depends on the dose (or magnitude) and duration of the perturbation. Homeostasis may be restored by self-repair, for example, via processes such as proliferation of affected cells or angiogenesis to create new vasculature. Transient or sustained BBB dysfunction may result in acute or pathological symptoms, for example, microhemorrhages or hypoperfusion. In more extreme cases, perturbations may lead to cytotoxicity and cell death, for example, through exposure to cytotoxic plaques.

The composition and abundance of microorganisms in the gastrointestinal tract of cows are complex and extensive, and they play a crucial role in regulating nutrient digestion, absorption, maintaining digestive tract stability, and promoting the production and health of the host. The fermentation carried out by these microorganisms in the gastrointestinal tract is fundamental to the health and productivity of cows. Rumen microorganisms produce the majority of enzymes required to break down feed substrates, such as cellulose, protein, lipids, and other plant materials, through fermentation. This process provides energy metabolism substrates that satisfy approximately 70% of the host’s energy requirements for physiological activities. Gut microorganisms primarily decompose cellulose that is difficult to digest in the rumen, thereby providing heat and energy to the hosts. Additionally, they have an impact on host health and productivity through their role in immune function. Understanding the composition and function of the cow gut microbiota can help regulate dairy cattle breeding traits and improve their health status. As a result, it has become a popular research topic in dairy cattle breeding. This article provides a review of the composition, structure, physiological characteristics, and physiological effects of the cow gut microbiota, serving as a theoretical foundation for future studies that aim to utilize the gut microbiota for dairy cattle breeding or improving production traits. It may also serve as a reference for research on gut microbiota of other ruminants.

Prophylactic HIV vaccines must elicit antibodies (Abs) against the virus envelope glycoproteins (Env) to effectively prevent HIV infection. We investigated a vaccine platform that utilizes immune complexes made of Env proteins gp120 and monoclonal Abs (mAbs) against different gp120 epitopes. We previously observed alterations in V3 antigenicity upon formation of certain gp120/mAb complexes and demonstrated the ability of these complexes to modulate the elicitation of V3 Ab responses. However, the effects on the V1V2 domain, an important target for Abs that correlate with vaccine-induced protection against HIV, have not been studied, nor have immune complex vaccines made with non-B subtype Env. This study compared subtypes B (JRFL) and CRF_01.AE (A244) Env gp120 proteins in complex with selected gp120-specific mAbs. Allosteric and antigenic changes were detected on these immune complexes, indicating that gp120/mAb interaction induces alterations on the Env surface that may modify the Env immunogenic properties. To evaluate this idea, mice were immunized with gp120/mAb complexes or their uncomplexed gp120 counterparts. The overall serum IgG titers elicited against gp120 were comparable, but a marked skewing toward V1V2 or V3 was evident and dependent on the gp120 strain and the specificity of the mAb used to form the complexes. Compared with uncomplexed gp120JRFL, gp120JRFL complexed with CD4bs or V1V2 mAbs, but not with C2 or V3 mAbs, elicited V3 Abs of greater titers and breadth, and Abs more capable of neutralizing tier 1 virus. Epitope mapping revealed a shift to a more conserved site in the V3 crown. However, the complexes did not enhance V1V2 Ab response, and the elicited V1V2 Abs were not cross-reactive. This profile contrasts with Ab responses to gp120A244/mAb complexes. Notably, gp120A244/mAb complexes induced higher levels of V1V2 Abs with some cross-reactivity, while also stimulating weak or strain-specific V3 Abs. Sera from gp120A244/mAb complex-immunized animals displayed no measurable virus neutralization but did mediate Ab-dependent cellular phagocytosis, albeit at levels similar to that induced by gp120A244 alone. These data indicate the potential utility of immune complexes as vaccines to shape Ab responses toward or away from Env sites of interest.