In the Supplementary Information, you'll find a summary of Professor Evelyn Hu's interview.

Early Pleistocene hominin fossils rarely exhibit butchery marks discernible by identification. In the Turkana region of Kenya, our taphonomic study of published hominin fossils uncovered potential cut marks on KNM-ER 741, a ~145-million-year-old proximal left tibia shaft, originating from the Okote Member of the Koobi Fora Formation. A Nanovea white-light confocal profilometer scanned a dental impression of the marks. This led to the creation of 3-D models, which were then meticulously measured and compared against an actualistic database of 898 individual tooth, butchery, and trample marks generated via controlled experimentation. Experimental reproductions align with the multiple ancient cut marks observed in this comparison. To the extent of our knowledge, these are the first and, to date, the only cut marks identified on a postcranial fossil of an early Pleistocene hominin.

The tragic impact of cancer is often magnified by the widespread nature of metastasis, leading to numerous fatalities. Although the molecular makeup of neuroblastoma (NB), a pediatric tumor, has been identified at the primary site, the bone marrow (BM), where NB metastasizes, is characterized by a significant lack of molecular understanding. Single-cell transcriptomic and epigenomic profiling was performed on bone marrow aspirates from 11 individuals, each possessing one of three major neuroblastoma subtypes. The results were contrasted with five age-matched, metastasis-free controls, before thorough single-cell analysis of tissue diversity and intercellular relationships. These analyses were complemented by functional validations. We demonstrate that the cellular adaptability of neuroblastoma (NB) tumor cells persists during metastasis, and the composition of tumor cells is contingent upon the specific NB subtype. Monocytes within the bone marrow microenvironment are targeted by NB cell signaling, specifically through the pathways of macrophage migration inhibitory factor and midkine. These monocytes exhibit both M1 and M2 features, displaying both pro- and anti-inflammatory responses, and expressing tumor-promoting factors similar to tumor-associated macrophages. The pathways and interactions discovered in our research provide a framework for therapeutic approaches that address tumor-microenvironment interplays.

Dysfunction within the inner hair cells, ribbon synapses, spiral ganglion neurons, and the auditory nerve contributes to the hearing impairment known as auditory neuropathy spectrum disorder (ANSD). Approximately one in seven thousand newborns displays abnormal auditory nerve function, contributing to a substantial portion—10% to 14%—of children's permanent hearing loss. Though we have previously established a correlation between the AIFM1 c.1265G>A variation and ANSD, the intricate mechanism responsible for this association involving AIFM1 remains poorly defined. Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) via the nucleofection method, leveraging episomal plasmids. The patient's induced pluripotent stem cells (iPSCs) were modified with CRISPR/Cas9 technology to produce isogenic iPSCs carrying corrected genes. Further differentiation of these iPSCs into neurons was achieved using neural stem cells (NSCs). An investigation into the pathogenic mechanism was undertaken within these neurons. The AIFM1 c.1265G>A variant, present in patient cells (PBMCs, iPSCs, and neurons), induced a novel splicing alteration (c.1267-1305del), producing AIF proteins with p.R422Q and p.423-435del mutations, which subsequently hindered AIF dimerization. Impaired AIF dimerization subsequently caused a reduction in the interaction affinity between AIF and the coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4). On one side, the import of ETC complex subunits into mitochondria was impeded, causing a subsequent rise in ADP/ATP ratio and an increase in reactive oxygen species levels. Differently, the binding of MICU1 to MICU2 was hampered, contributing to a calcium overload in the cells. mCa2+ activated calpain, which then cleaved AIF, resulting in its nuclear transport and ultimately causing caspase-independent apoptosis. Interestingly, the repair of the AIFM1 variant profoundly restored the structural integrity and function of AIF, ultimately advancing the physiological well-being of patient-specific induced pluripotent stem cell-derived neurons. This study's findings indicate that the AIFM1 variant plays a pivotal role in the molecular basis of ANSD. mCa2+ overload, a consequence of mitochondrial dysfunction, plays a substantial part in AIFM1-related ANSD. The elucidation of ANSD's mechanisms, as revealed by our research, may unlock the development of new therapies.

By interacting with exoskeletons, human behavior modification is attainable, which is applicable to physical rehabilitation or skill enhancement. Although robotic design and control have seen substantial progress, their use in human training programs is still restricted. Foremost impediments to designing such training paradigms involve accurately predicting the effects of human-exoskeleton interaction and choosing the right interactive controls to influence human behavior. We present, in this article, a technique for demonstrating changes in human behavior when using an exoskeleton, and associating these changes with expert performance related to the task's objective. We analyze how human-exoskeleton interactions during learning influence the joint coordinations of the robot, which are also termed kinematic coordination behaviors. Kinematic coordination behaviors are showcased within two task domains, with three human-subject studies as evidence. Participants learning new tasks within the exoskeleton setting demonstrate consistent coordinated movements, elevating their skill to use these coordination patterns for better results, and ultimately converging towards analogous coordinated approaches to a specific task across participants. From a broad perspective, we pinpoint specialized joint coordinations, employed by various experts, for a particular task objective. Quantifying these coordinations involves observing expert performances; the resemblance to these coordinations serves as a metric for novice learning throughout training. Expert coordinations observed can be further applied in designing adaptive robot interactions to teach a participant expert behaviors.

The persistent quest for high solar-to-hydrogen (STH) efficiency, coupled with enduring durability, using inexpensive and scalable photo-absorbers, remains a significant hurdle. The conductive adhesive barrier (CAB) detailed here, through its design and construction, efficiently translates more than 99% of photoelectric power to chemical reactions. Photoelectrochemical cells based on halide perovskites, facilitated by the CAB, showcase record efficiencies in solar-to-hydrogen conversion with two distinct designs. HG106 A co-planar photocathode-photoanode architecture, the first, displayed an STH efficiency of 134% and a t60 of 163 hours, a figure solely constrained by the hygroscopic hole transport layer within the n-i-p device. Airborne microbiome A monolithic stacked silicon-perovskite tandem solar cell, in its second design, achieved a peak short-circuit current efficiency of 208% and continuously functioned for 102 hours under AM 15G illumination, before a 60% decline in its power output was observed. These advancements promise efficient, durable, and inexpensive solar-powered water-splitting technology equipped with multifunctional barriers.

Cellular signaling pathways feature the serine/threonine kinase AKT as a core component and central regulator. The development of a variety of human diseases is often underpinned by aberrant AKT activation, however, the exact manner in which different patterns of AKT-dependent phosphorylation influence downstream signalling and ensuing phenotypes is still largely unknown. Utilizing a systems-level analysis which combines optogenetics, mass spectrometry-based phosphoproteomics, and bioinformatics, we explore how diverse Akt1 stimulation intensities, durations, and patterns dictate distinct temporal phosphorylation profiles in vascular endothelial cells. Light-stimulated phosphorylation at approximately 35,000 sites across multiple conditions allows us to identify signaling pathways activated by Akt1. We also explore how Akt1 signalling integrates with growth factor signalling in endothelial cells. Our research also groups kinase substrates that are preferentially activated by pulsating, temporary, and continuous Akt1 signals. We identify a list of phosphorylation sites exhibiting covariation with Akt1 phosphorylation across diverse experimental conditions, thus categorizing them as potential Akt1 substrates. Future research on AKT signaling and its dynamic behavior can utilize our comprehensive dataset.

Posterior lingual glands are grouped under the designations of Weber and von Ebner glands. Glycans are integral to the intricate workings of salivary glands. While glycan distribution illuminates functional variations, the developing rat posterior lingual glands remain shrouded in uncertainty. This study's focus was on investigating the relationship between posterior lingual gland maturation and activity in rats, employing a histochemical analysis involving lectins that bind to sugar moieties. Aging Biology Serous cells in adult rats were observed in association with Arachis hypogaea (PNA), Glycine maximus (SBA), and Triticum vulgaris (WGA), whereas Dolichos biflorus (DBA) was found alongside mucous cells. During the early developmental phases of both Weber's and von Ebner's glands, all four lectins were associated with serous cells. Subsequently, as development progressed, DBA lectin became absent from serous cells, appearing exclusively in mucous cells. Development in its initial phase shows Gal (13)>Gal (14)>Gal, GalNAc>Gal>GalNAc, NeuAc>(GalNAc)2-3>>>GlcNAc, and GalNAc(13) expression. Yet, GalNAc(13) is downregulated in serous cells and appears exclusively in mucous cells in a mature state.