bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances and Challenges in Zone 2 Flexor Tendon Repairs
Authors: Wimbiscus Mae , Sullivan Lauren , Lee Justin , Vinson Ariel , Torres-Guzman Ricardo A. , Stehr Justin , Bhandari Laxminarayan
Published: November 2024

Flexor zone 2 is the area between the A1 pulley at the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at A4 pulley. Termed “no man's land,” primary repair at zone 2 had notoriously high rate of complications such as adhesions, contractures, and tendon rupture. Improved understanding of tendon healing, stronger suture materials, novel operative techniques, judicious pulley venting, and early active rehabilitation have helped improve outcomes. This review examines current methodologies and postoperative considerations for zone 2 flexor tendon repair.
Management of Distal Radius Rim Fractures—Technical Pearls
Authors: Shi Tiffany , Sullivan Lauren , Qazi Uzair , Bhandari P. Laxminarayan
Published: November 2024

Distal radius fractures are common and vary based on their fracture pattern. Fractures distal to the watershed line are called rim fractures or marginal fractures. In addition to challenges already faced when treating distal radius fractures at other sites, rim fractures pose particular challenges in proper identification, reduction, and stabilization. This article reviews this specific subset of distal radius fractures and its management.
Vanderbilt University Rehabilitation Approach to Zone 2 Tendon Repairs in the Hand
Authors: Stehr Justin , Wimbiscus Mae , Sullivan Lauren E. , Torres-Guzman Ricardo A. , Bhandari Panambur
Published: November 2024

Zone 2 of the hand, which stretches from the region between the A1 pulley at the distal palmar crease to the insertion of the FDS tendon at the end of the A4 pulley, is notable for its high complication rate following surgery. Many of these complications, such as adhesions, contractures, and tendon rupture, can be avoided through adequate rehabilitation. We document the rehabilitation protocol at Vanderbilt University Medical center, which is characterized by 4 phases. An initial postoperative phase emphasizes shielding the flexor tendons with little motion, a second phase focuses on an orthosis to keep the metacarpophalangeal joints flexed at 45 degrees, a third phase focuses on strengthening exercises, and a fourth phase that focuses on transitioning to normal activities without restriction.
Craniosynostosis
Authors: Sullivan Lauren E. , Li Ruoying , Tong Victoria S. , Jagasia Puja , Bonfield Christopher M. , Golinko Michael S. , Pontell Matthew E.
Published: November 2024

Craniosynostosis is characterized by the premature fusion of one or more cranial sutures, which can lead to abnormal skull shape and restricted skull growth. Although most cases are present in isolation, some are associated with genetic syndromes, such as Pfeiffer, Muenke, Couzon, Apert, and others, which increases the complexity of care. Today, a spectrum of surgical options to treat craniosynostosis are available and range from traditional open cranial vault remodeling to newer and less invasive suturectomy-based techniques. Which procedure is offered to a patient depends on not only the specific synostosis pattern but also factors such as patient age, the need for additional procedures or interventions, and evidence of elevated intracranial pressure. Thorough consultations with families to discuss achievable goals for cosmesis and function are essential in providing optimal care to each impacted child.
Radial Longitudinal Deficiency
Authors: Bhat Anil K. , Pai G Mithun
Published: November 2024

Radial longitudinal deficiency (RLD) is a multidimensional congenital hand difference encompassing skeletal, musculotendinous, and joint components. Managing RLD remains challenging, with numerous surgical procedures over the past century failing to achieve a stable, mobile, growing wrist without recurrence of the deformity. This review investigates new therapeutic approaches for RLD, delving into genetic, embryological, and histological aspects, including proximal muscle involvement and causes of recurrence.

A notable association between RLD and preaxial polydactyly, linked to aberrations in the Sonic Hedgehog signaling pathway, is highlighted, suggesting a common embryonic origin. Experimental evidence indicates that ectopic Sonic Hedgehog signaling can result in radial aplasia and preaxial polydactyly. Histopathological studies revealed significant muscle abnormalities in RLD, contributing to deformities and recurrences.

Techniques such as preoperative soft tissue distraction show promise, but recurrence rates persist. Alternative surgical procedures, such as vascularized second metatarsophalangeal joint transfer and ulna cuff osteotomy, offer potential improvements by minimizing recurrence and optimizing limb length.

Despite advancements, effective management of RLD requires further research into the interplay between genetic factors, muscle abnormalities, and surgical outcomes. This review underscores the importance of early detection, genetic counseling, and a multidisciplinary approach to enhance long-term functional and aesthetic results for RLD patients.
Assessing the measurement invariance of Free Will and Determinism Plus scale across four languages: a registered report
Authors: Duan Siqi , Zhou Chenghao , Liu Qinglan , Gong Yixin , Dou Zenan , Li Jingguang , Chuan-Peng Hu
Published: November 2024

Free will is assumed to be the core of an individual’s self-concept. Belief in free will has been studied extensively and was found to be correlated with many behavioural and psychological outcomes. Although developed and validated in the West, the Free will and Determinism Plus (FAD-Plus) scale has been translated, used, and interpreted as a measurement of free will beliefs in multiple cultures. However, the cross-cultural measurement invariance of FAD-Plus has not been examined. Given the cultural differences in understanding the concept of ‘free will’, items of FAD-Plus may have different interpretations in different cultures, which may compromise its cross-cultural measurement invariance. To provide empirical evidence for the lack of cross-cultural measurement invariance, we collected data in China and analyzed these data together with open datasets of FAD-Plus in three other languages: Japanese, French and English. We only found partial measurement invariance between the Chinese and English datasets, as well as the Japanese and English datasets. These results provided the first assessment of cross-cultural measure invariance of FAD-Plus. We discussed the potential implications of the current study for future studies in the field.
A comparative in silico analysis of the vlhA gene regions of Mycoplasma gallisepticum  and Myc. synoviae isolates from commercial hen farms in Mexico.

Authors: Maya Linda , Gómez-Verduzco Gabriela , Trigo-Tavera Francisco J. , Moreno-Fierros Leticia , Rojas-Trejo Verónica , Miranda-Morales Rosa Elena
Published: November 2024

Avian mycoplasmosis, caused by Mycoplasma synoviae and Mycoplasma gallisepticum, poses significant economic challenges due to respiratory issues, reduced egg production, and soft eggshells. The variable lipoprotein haemagglutinin (VlhA) protein, crucial for pathogenicity, comprises conserved (MSPB) and variable (MSPA) regions. The aim of this study was to identify the conserved region of vlhA gene sequences in field strain. We examined vlhA sequences from field strains collected in central Mexico (Jalisco and Mexico City). Specifically, we analysed 124 deformed eggs and 10 laying hens from 9 farms with Hy-line and Bovans breeds. Using polymerase chain reaction (PCR) targeting the mgc2 and 16S ribosomal RNA (rRNA) genes, we characterised 24 field strains, 4 of which were Myc. synoviae and 20 of which were Myc. gallisepticum (20). We analysed the vlhA regions, based on the AF035624.1 reference sequence, with ATTC strains as positive controls. Additionally, we validated the PCR with 20 negative samples from Mycoplasma isolation without the need of cultivation. We identified two amplification regions: MSPB and MSPA. Bioanalysis revealed relationships between our field samples and avian Mycoplasma sequences in GenBank, alongside similarities with lipoproteins present in Acholeplasma laidlawii PG8 and Escherichia coli. Given the significance of the VlhA protein in pathogenicity and immune evasion, the identified conserved sequences hold potential as therapeutic targets and for phylogenetic studies.
The
Rickettsia
actin-based motility effectors RickA and Sca2 contribute differently to cell-to-cell spread and pathogenicity
Authors: Tran Cuong J. , Zubair-Nizami Zahra , Langohr Ingeborg M. , Welch Matthew D.
Published: November 2024

Rickettsia parkeri
is an obligate intracellular, tick-borne bacterial pathogen that can cause eschar-associated rickettsiosis in humans.
R. parkeri
invades host cells, escapes from vacuoles into the cytosol, and undergoes two independent modes of actin-based motility mediated by effectors RickA or Sca2. Actin-based motility of
R. parkeri
enables bacteria to enter protrusions of the host cell plasma membrane that are engulfed by neighboring host cells. However, whether and how RickA and Sca2 independently contribute to cell-to-cell spread
in vitro
or pathogenicity
in vivo
has been unclear. Using live cell imaging of
rickA
::Tn and
sca2
::Tn mutants, we discovered both RickA and Sca2 contribute to different modes of cell-to-cell spread. Compared with Sca2-spread, RickA-spread involves the formation of longer protrusions that exhibit larger fluctuations in length and take a longer time to be engulfed into neighboring cells. We further compared the roles of RickA and Sca2
in vivo
following intradermal infection of
Ifnar1
-/-
;
Ifngr1
-/-
double-knockout mice, which exhibit eschars and succumb to infection with wild-type
R. parkeri
. We observed that RickA is important for severe eschar formation, whereas Sca2 contributes to larger foci of infection in the skin and dissemination from the skin to the internal organs. Our results suggest that actin-based motility effectors RickA and Sca2 drive two distinct forms of cell-to-cell spread and contribute differently to pathogenicity in the mammalian host.
T cell mediated impairment of epithelial integrity in Crohn’s disease
Authors: Hamoudi Sarah , Hammoudi Nassim , Bonnereau Julie , Sonn Anthony , Capelle Elisabeth , Bezault Madeleine , Chardiny Victor , Bonnet Joëlle , Minh My-Linh Tran , Gornet Jean-Marc , Baudry Clotilde , Corte Hélène , Maggiori Léon , Toubert Antoine , Becht Etienne , Allez Matthieu , Bourhis Lionel Le
Published: November 2024

T lymphocytes play a major role in intestinal homeostasis, with a particular impact on the balance between self-renewal and differentiation of intestinal epithelial cells (IECs). In Crohn’s disease (CD) patients, the intestinal mucosa is inflamed, epithelium permeability is increased, and IECs present compositional and functional defects. The role of T lymphocytes interactions with IECs in the physiopathology of CD remains in question. Here, we use a three-dimensional human autologous coculture model between purified intestinal organoids derived from primary tissues of CD and non-inflammatory control patients, and mucosal T lymphocytes extracted from the same location. We show that while in homeostatic context T cells support the proliferation and differentiation balance of organoids, mucosal T lymphocytes from CD patients present a high cytotoxicity against IECs. Importantly, this cytotoxicity is a persistent defect overtime in culture. Organoids also show defective intestinal stem cells (ISCs) proliferation and morphological changes. Single cell RNA sequencing after coculture highlights a general response of T cells to the epithelial microenvironment, and more particularly, an increase activation of a pro-inflammatory CD8+ T cells effector population in CD patients compared to controls.

Graphical abstract
Resting After Learning Facilitates Memory Consolidation and Reverses Spatial Reorientation Impairments in ‘New Surroundings’ in 3xTg-AD Mice
Authors: Stimmell A. C. , Alday L. J. , Marquez Diaz J. , Moseley S. C. , Cushing S. D , Salvador E. M. , Ragsdale S. M. , Wilber A. A.
Published: November 2024

Sleep is an essential component of productive memory consolidation and waste clearance, including pathology associated with Alzheimer’s disease (AD). Facilitation of sleep decreases Aβ and tau accumulation and is important for the consolidation of spatial memories. We previously found that 6-month female 3xTg-AD mice were impaired at spatial reorientation. Given the association between sleep and AD, we assessed the impact of added rest on impaired spatial reorientation that we previously observed. We randomly assigned 3xTg-AD mice to a rest (n=7; 50 min pre- & post-task induced rest) or a non-rest group (n=7; mice remained in the home cage pre- & post-task). Mice in both groups were compared to non-Tg, age-matched, non-rest controls (n=6). To confirm that our sleep condition induced sleep, we performed the same experiment with rest sessions for both 3xTg-AD and non-Tg mice (n=6/group) implanted with recording electrodes to capture local field potentials (LFPs), which were used to classify sleep states. Markers of pathology were also assessed in the parietal-hippocampal network, where we previously showed pTau positive cell density predicted spatial reorientation ability (pTau, 6E10, M78, and M22). However, we found that 3xTg-AD rest mice were not impaired at spatial reorientation compared to non-Tg mice and performed better than 3xTg-AD non-rest mice (replicating our previous work). This recovered behavior persisted despite no change in the density of pathology positive cells. Thus, improving sleep in early stages of AD pathology offers a promising approach for facilitating memory consolidation and improving cognition.
Occurrence of a ‘CandidatusPhytoplasma pruni’-Related Strain Associated with Commercial Poinsettias in Turkey
Authors: Benlioglu Kemal , Ozyilmaz Umit , Yurttas Huseyin Faruk
Published: November 2024

The poinsettia (Euphorbia pulcherrimaWilld. ex Klotzsch.) is one of Turkey’s most important potted ornamental crops. Potted poinsettia plants exhibiting smaller-sized brilliant red bracts against the green leaves with free-branching were collected from commercial florists in three provinces of Turkey. In iPhyClassifier analysis, the query 16SrDNA sequences of our isolates shared 99.58% identity with that of theCandidatusPhytoplasma pruni. Our leaf samples consistently yielded a product of 0.7 kb by PCR with primers (KFD4F/KFD4R), which was newly designed based on X-Disease group (16SrIII) of phytoplasma secY sequences available in GenBank. The partial 16S rRNA sequences were used for phylogenetic analyses covering 41 taxa from the group of 16SrIII’Candidatus Phytoplasma’ strains, including 14 strains causing disease on poinsettia worldwide. The sequences that caused the same disease in poinsettia plants in Finland, the USA, Mexico, Taiwan, Japan, Korea, and Canada, including three strains from Turkey, formed a mono-phylogenetic group with a support value of 87%.
The association of Mediterranean plant species with herbivorous arthropods and its effect on pest abundance in organic vineyards
Authors: Santos Renata , Naves Pedro , Morais Rita , Rodrigues Leonor R. , Pina Sílvia , Santos Márcia , Rebelo Maria Teresa , Pereira Patrícia Garcia , Magalhães Sara , Figueiredo Elisabete
Published: November 2024

Non-crop plant resources, such as hedgerows and adjacent woodland areas, may impact the distribution of pest species in the crop. Knowledge on the associations between plants and arthropods as well as their impact on pest distribution is thus key to adequately manage agroecosystems. We selected a number of native Mediterranean plant species located around organic vineyards in Southern Portugal and determined their associations with species of Auchenorrhyncha and phytophagous tetranychid and tenuipalpid mites, including the main species of vineyard pests in the area. We also tested if the abundance of vineyard pests is affected by the distance to the edge and the species of plants present. Most non-crop plants and ground cover vegetation harbored very low numbers of leafhopper pests.Rubus ulmifoliusandTamarix africanaproved to be a repository of non-pest Auchenorrhyncha species, with the former also serving as winter repository of the pestJacobiasca lybica. Rosa caninaandFraxinus angustifoliahosted abundant populations of the spider miteTetranychus urticae. Still, plots next to plant biodiverse margins harbored fewer numbers ofT. urticae, when compared with plots next to other vineyards. Furthermore, pest abundance in vineyards increased with growing distance to plant biodiverse margins. Our results high-light the benefits of biodiverse margins in reducing pest abundance and point to the importance of a good selection of plant species when managing and planning these non-crop plant resources.
Computer method of biocenotic zoning
Authors: Sukhanov V.V.
Published: November 2024

Algorithm of dividing a territory or a water area into homogeneous areas is described. This area has its own group of communities, similar to each other in terms of species structure. Quantitative statistical indicator, describing quality of such zoning, is proposed. Three examples are given: tree communities in the reserve, nekton in the Sea of Okhotsk and taxocenes of insect larvae in the forest river. Difficulties in the process and interpretation of zoning results, recipes and ideas to solve these problems are discussed.
Subcortical nuclei of the human ascending arousal system encode anticipated reward but do not predict subsequent memory
Authors: Lloyd Beth , Miletić Steven , Bazin Pierre-Louis , Isherwood Scott , Tse Desmond H. Y. , Håberg Asta , Forstmann Birte , Nieuwenhuis Sander
Published: November 2024

Subcortical nuclei of the ascending arousal system play an important role in regulating brain and cognition. However, functional MRI of these nuclei in humans involves unique challenges due to their size and location deep within the brain. Here, we used ultra-high-field MRI and other methodological advances to investigate the activity of six subcortical nuclei during reward anticipation and memory encoding: the locus coeruleus, basal forebrain, median and dorsal raphe nuclei, substantia nigra and ventral tegmental area. Participants performed a monetary incentive delay task, which successfully induced a state of reward anticipation, and a 24-hour delayed surprise memory test. Region-of-interest analyses revealed that activity in all subcortical nuclei increased in anticipation of potential rewards as opposed to neutral outcomes. In contrast, activity in none of the nuclei predicted memory performance 24 hours later. These findings provide new insights into the cognitive functions that are supported by the human ascending arousal system.
Timely neurogenesis enables increased nuclear packing order during neuronal lamination
Authors: Ferme Lucrezia C. , Ryan Allyson Q. , Haase Robert , Modes Carl D. , Norden Caren
Published: November 2024

The coordination of cell proliferation, migration, and differentiation is crucial for organogenesis in many tissues, including the central nervous system and other organs that arise from pseudostratified epithelia (PSE). PSE feature densely packed elongated epithelial cells, with nuclei positioned along the apicobasal cell axis in a cell cycle-dependent manner. Also, PSE serve as organ precursors in diverse developmental contexts across evolution. While the role of nuclear movements in PSE has been extensively studied, less is known about whether and how their nuclear packing arrangements and changes of packing state influence tissue morphogenesis. To address this, we analyzed nuclear shapes, sizes and neighborhood statistics by segmenting nuclei in 3D and over development in zebrafish retinal neuroepithelia (RNE). We find that in PSE nuclei exhibit orientational, nematic-like order but remain positionally disordered. This pattern is conserved in other, less packed, neuroepithelia, like the hindbrain, suggesting that nematic-like order is a hallmark of pseudostratification. Our analysis during retinal development also revealed that nuclear packing density increases, approaching theoretical packing limits for disordered monodisperse ellipsoids at stages when the tissue transitions to a laminated neuronal structure. As neurogenesis progresses, nuclear shapes are remodeled, enabling the RNE to shift to a crystalline, ordered structure, while maintaining orientational alignment. Failure to initiate neurogenesis results in severe tissue deformations due to increased buckling instability. Our results thus show an instance where nuclear shape and nuclear positioning and their changes are essential for proper retinal morphogenesis, a phenomenon most likely also found in other tissue arrangements.
Sex-Related Gene Expression in the Posterodorsal Medial Amygdala of Cycling Female Rats Along with Prolactin Modulation of Lordosis Behavior
Authors: Bühler Letícia , de Moura Ana Carolina , Giovenardi Márcia , Goffin Vincent , Rasia-Filho Alberto A.
Published: November 2024

The rat posterodorsal medial amygdala (MePD) is sexually dimorphic, has a high concentration of receptors for gonadal hormones and prolactin (PRL), and modulates reproduction. To unravel genetic and functional data for this relevant node of the social behavior network, we studied the expression ofERα, ERβ, GPER1, Kiss1, Kiss1R, PRGR, PRL, PRLR, EGR1, JAK2, STAT5A,andSTAT5Bin the MePD of males and females along the estrous cycle using the RT-qPCR technique. We also investigated whether PRL in the MePD would affect the sexual behavior display of proestrus females by microinjecting saline, the PRL receptor antagonist Del1-9-G129R-hPRL (1 µM and 10 µM), or PRL (1 nM) and Del1-9-G129R-hPRL (10 µM) 3h before the onset of the dark-cycle period. The estrogen-dependent lordosis behavior, indicative of sexual receptivity of proestrus females, was recorded and compared before (control) and after (test) microinjections in these groups. Sex differences were found in the right and left MePD gene expression.ERαandKiss1R,as well asPRL, Short PRLR, andSTAT5Bexpression, is higher in cycling females than males.Kiss1expression is higher in males than females, andGPER1is higher during diestrus than proestrus. Furthermore, Del1-9-G129R-hPRL in the MePD significantly reduced the full display and quotient of lordosis in proestrus females, an effect restored by the co-microinjection of PRL. In conjunction, the expression of studied genes showed specific sex and estrous cycle phase features while, in proestrus, PRL action in the MePD plays an essential role in the display of lordosis during the ovulatory period.

Highlights

The MePD expression ofKiss1is higher in males than females.

ERαandKiss1Rexpression is higher in cycling females than males.

PRL, Short PRLR,andSTAT5Bexpression is higher in cycling females than males.

GPER1expression is higher during diestrus than in proestrus.

Del1-9-G129R-hPRL action in the MePD reduced lordosis quotient during proestrus.
Sex-specific Regulation of Fentanyl Reward by the Circadian Transcription Factor NPAS2
Authors: Barko Kelly , Shelton Micah A. , DePoy Lauren M. , Gayden-Kozel Jenesis , Kim Sam-Moon , Puig Stephanie , Xue Xiangning , Parekh Puja K. , Tseng George C. , Williams Benjamin R. , Oliver-Smith Jeffrey , Zhu Xiyu , Freyberg Zachary , Logan Ryan W.
Published: November 2024

Synthetic opioids like fentanyl are highly potent and prevalent in the illicit drug market, leading to tolerance, dependence, and opioid use disorder (OUD). Chronic opioid use disrupts sleep and circadian rhythms, which persist even during treatment and abstinence, increasing the risk of relapse. The body’s molecular clock, regulated by transcriptional and translational feedback loops, controls various physiological processes, including the expression of endogenous opioids and their receptors. The circadian transcription factor NPAS2, highly expressed in the nucleus accumbens, may have a crucial function in opioid-related behaviors. Our study found sex-specific roles for NPAS2-mediated reward behaviors in male and female mice, including in fentanyl seeking and craving. We also identified specific cell types and transcriptional targets in the nucleus accumbens of both mice and humans by which NPAS2 may mediate the impact of fentanyl on brain physiology and in opioid reward-related behaviors. Ultimately, our findings begin to uncover the mechanisms underlying circadian rhythm dysfunction and opioid addiction.
Volumetric and Diffusion Tensor Imaging biomarkers indicating long lasting post-concussion abnormalities in a youth pig model of mild Traumatic Brain Injury
Authors: Sanjida Islam , Alesa Netzley , Chenyang Li , Jiangyang Zhang , Bianca Dávila-Montero , Ana Vazquez , Shaun Subbaiah , Avner Meoded , Kirk Munoz , Aimee Colbath , Jie Huang , Ricardo Mejia-Alvarez , Jane Manfredi , Galit Pelled
Published: November 2024

Mild Traumatic Brain Injury (mTBI) caused by sports-related incidents in children and youth can lead to prolonged cognitive impairments, underscoring the importance of improved diagnosis and comprehension of its enduring impacts on neuropathology. A pig model was chosen for its similarities to the human brain in terms of gyrencephalic structure, size, and regional proportions, and a closed-head mTBI was induced in adolescent pigs. In this study, 12 (n=4 male and n=8 female) 16-weeks old Yucatan pigs were tested; n=6 received mTBI and n=6 received a Sham procedure. This study utilized T1-weighted imaging to assess volumetric alterations in different regions of the brain and diffusion tensor imaging (DTI) to examine microstructural damage in white matter. The pigs were imaged at one and three months post-injury. Our volumetric analysis of key white and gray matter regions showed significant longitudinal changes in pigs with mTBI compared to sham controls. The observed volume increases may be attributed to swelling, neuroinflammation, or hyperactivity. Fractional anisotropy (FA) values derived from DTI images demonstrated an increase in corpus callosum from 1 month to 3 months only in mTBI pigs. Additionally, comparisons of the left and right internal capsules revealed a decrease in FA in the right internal capsule for mTBI pigs, likely due to the impact being slightly localized to the right side of the brain, which may indicate demyelination. Thus, the injury has disrupted the maturation of white and gray matter of the developing brain. This signifies the need for longitudinal investigations after mTBI to comprehensively assess its long-term effects and contribute to the clinical management of concussion in youth.
UCE phylogenomics inform the systematics and geographic range evolution of the harvester ant genusPogonomyrmex
Authors: Graber Leland C. , Johnson Robert A. , Moreau Corrie S.
Published: November 2024

The harvester ant genusPogonomyrmexis common in arid regions of North America, South America, and Hispaniola. Here, we use ultraconserved elements (UCEs) to infer the most comprehensive phylogeny of the genus to date. Our inferred topology largely supports previously hypothesizedPogonomyrmexevolutionary relationships and species groups. Our divergence dating analysis substantially pushes back the age of bothPogonomyrmexand the Pogonomyrmecini tribe, suggesting an early Eocene origin forPogonomyrmex. We infer thatPogonomyrmexlikely originated within the Pacific dominion ecoregion of Northern South America.Pogonomyrmex(excluding thePogonomyrmex mayriclade) likely adapted to cooler and drier climates in the middle Eocene. The genus spread to North America in the late Eocene, likely aided by the ephemeral volcanic islands of the Panama Arc. A smaller group ofPogonomyrmexdispersed to Mesoamerica and North America in the Oligocene and to Hispaniola in the Miocene, most likely out of Mesoamerica. Our results suggest that adaptations to arid environments allowedPogonomyrmexto spread and diversify in regions of the Americas that were actively becoming cooler and drier due to orogeny and other geologic processes.
Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab resistant HER2 positive breast cancer
Authors: Hua Yijia , Duan Ningjun , Sun Chunxiao , Yang Fan , Tian Min , Sun Yanting , Zhao Shuhan , Gong Jue , Liu Qian , Huang Xiang , Liang Yan , Fu Ziyi , Li Wei , Yin Yongmei
Published: November 2024

Trastuzumab resistance remains a challenge for HER2 positive breast cancer treatment. Targeting metabolic reprogramming would provide novel insights for therapeutic strategies. Here, we integrated metabolomics, transcriptomics and epigenomics data of trastuzumab sensitive and primary resistant HER2 positive breast cancer to identify metabolic alterations. Aberrant cysteine metabolism was discovered in trastuzumab primary resistant breast cancer at both circulating and intracellular levels. The inhibition of SLC7A11 and cysteine starvation could synergize with trastuzumab to induce ferroptosis. Mechanistically, increased H3K4me3 and decreased DNA methylation enhanced SLC7A11 transcription and cystine uptake in trastuzumab resistant breast cancer. The regulation of epigenetic modifications modulated cysteine metabolism and ferroptosis sensitivity. These results revealed an innovative approach for overcoming trastuzumab resistance by targeting specific amino acid metabolism.
Novel function ofHox13in regulating outgrowth of the newt hindlimb bud through interaction withFgf10andTbx4
Authors: Tozawa Sayo , Matsubara Haruka , Minamitani Fumina , Kamei Yasuhiro , Saida Misako , Asao Momoko , Suzuki Ken-ichi T. , Matsunami Masatoshi , Shigenobu Shuji , Hayashi Toshinori , Abe Gembu , Takeuchi Takashi
Published: November 2024

5’Hoxgenes regulate pattern formation along the axes of the limb. Previously, we showed thatHoxa13/Hoxd13double mutant newts lacked all digits of the forelimbs during development and regeneration, showing that newtHox13is necessary for digit formation in development and regeneration. In addition, we found another unique phenotype. A part of theHox13crispant newts showed hindlimb defects, in which whole or almost whole hindlimbs were lost, suggesting a novel function ofHox13in limb development. Using germline mutants, we showed that mutation inHox13led to hindlimb defects. The limb buds ofHox13crispants formed, however, did not show outgrowth. Expression ofFgf10andTbx4, which are involved in limb outgrowth, decreased in the hindlimb buds ofHox13crispants. In addition, hindlimb defects were observed in bothFgf10andTbx4crispant newts. Finally,Fgf10andTbx4interacted withHox13genetically. Our results revealed a novel function ofHox13in regulating the outgrowth of the newt hindlimb bud through interaction withFgf10andTbx4.
YORU: social behavior detection based on user-defined animal appearance using deep learning
Authors: Yamanouchi Hayato M , Takeuchi Ryosuke F , Chiba Naoya , Hashimoto Koichi , Shimizu Takashi , Tanaka Ryoya , Kamikouchi Azusa
Published: November 2024

The creation of tools using deep learning methodologies for animal behavior analysis has revolutionized neuroethology. They allow researchers to analyze animal behaviors and reveal causal relationships between specific neural circuits and behaviors. However, the application of such annotation/manipulation systems to social behaviors, in which multiple individuals interact dynamically, remains challenging. Here, we applied an object detection algorithm to classify animal social behaviors. Our system, packaged as “YORU” (Your Optimal Recognition Utility), classifies animal behaviors, including social behaviors, based on the shape of the animal as a “behavior object”. It successfully classified several types of social behaviors ranging from vertebrates to insects. We also integrated a closed-loop control system for operating optogenetic devices into the YORU package. YORU enables real-time delivery of photostimulation feedback to specific individuals during specific behaviors, even when multiple individuals are close together. We hope that the YORU system will accelerate the understanding of the neural basis of social behaviors.
Bidirectional Impact of miR-29a modulation on Memory Stability in the Adult Brain
Authors: Viglione Aurelia , Giannuzzi Chiara , Putignano Elena , Mazziotti Raffaele , Cellerino Alessandro , Pizzorusso Tommaso
Published: November 2024

MicroRNAs are key regulators of brain gene expression, with miR-29a notably upregulated from development to adulthood and in aging, and showing links to cognitive decline. However, the extent to which miR-29 levels influence learning and memory processes, and its molecular mediators, remains to be determined. Here, we down- and up-regulated miR-29a levels in the dorsal hippocampus of adult mice to reveal miR-29 role in memory. Inhibiting miR-29a enhanced trace fear memory stability, increased Dnmt3a levels, and affected CpG methylation in gene regulation regions. In contrast, increasing miR-29a impaired memory performances and decreased Dnmt3a levels, suggesting a destabilization of memory processes. Proteomic and transcriptomic analysis demonstrated that miR-29a antagonism upregulated RNA-binding and synaptic proteins and downregulated inflammation and myelin associated proteins. These results underscore miR-29a’s pivotal role in memory persistence, plasticity, and cognitive aging, suggesting that miR-29a modulation could offer potential strategies for cognitive enhancement and age-related memory decline.
Transmission dynamics of COVID-19 in the outbreak among healthcare workers at a university hospital in Rio de Janeiro, Brazil
Authors: Braga José Ueleres , Rocco Suassuna José Hérmogennes , Semeão de Souza Ana Sara
Published: November 2024

Objective

The objective of this study was to investigate an outbreak of COVID-19 among HCWs in the nephrology service of a university hospital in Rio de Janeiro in March 2020.

Methods

The study population consisted of a team of 59 HCWs, and surveys were conducted through digital interviews. Signs and symptoms, existence of comorbidities, hospitalization, and the network of contacts among the professionals during the period from March 1 to 23, 2020 were evaluated. The analysis consisted of: (i) describe epidemic curve, (ii) transmission chains, (iii) estimate the effective reproduction number (Rt), and (iv) identification of factors related to infectious cases.

Results

Of the 59 professionals in the nephrology service, 43 (73%) participated in the study. The first case occurred on March 1 and the last case occurred on March 23, 2020. The outbreak peaked on March 12–13. 31 participants were probable or confirmed cases COVID-19. These were mostly women (71%), with an average age of 37 years, and were predominantly doctors (45%). Only one participant was hospitalized. The risk factors for contracting COVID-19 were being a medical doctor, working at another hospital, and being female.

Conclusion

We concluded that there was an outbreak of COVID-19 among health professionals in the nephrology service at HUPE from March 1 to 23, 2020. The transmission chain network had large clusters showing intense transmission.
Lipid flippases ATP9A and ATP9B form a complex and contribute to the secretory pathway from the Golgi apparatus
Authors: Yagi Tsukasa , Nakabuchi Riki , Muranaka Yumeka , Tanaka Gaku , Nakayama Kazuhisa , Takatsu Hiroyuki , Shin Hye-Won
Published: November 2024

Type IV P-type ATPases (P4-ATPases) serve as lipid flippases, translocating membrane lipids from the exoplasmic (or luminal) leaflet to the cytoplasmic leaflet of lipid bilayers. In mammals, these P4-ATPases are localized to distinct subcellular compartments. ATP8A1 and ATP9A, both members of the P4-ATPase family, are involved in endosome-mediated membrane trafficking, although the roles of P4-ATPases in the secretory pathway remain to be clarified. ATP9A and ATP9B are located in thetrans-Golgi network, with ATP9A also present in endosomal compartments. This study unveiled the overlapping roles of ATP9A and ATP9B in transporting VSVG from the Golgi to the plasma membrane within the secretory pathway. Furthermore, we demonstrated that the flippase activities of ATP9A and ATP9B were crucial for transport process. Notably, we discovered the formation of homomeric and/or heteromeric complexes between ATP9A and ATP9B. The existence of the heteromeric complex notably contributed to the retention of ATP9A in the Golgi. Therefore, ATP9A and ATP9B play a role in the secretory pathway from the Golgi to the plasma membrane, forming either homomeric or heteromeric complexes.
Confirming the Impact of Climate Change on Biodiversity: Results from a Global Survey
Authors: Alshehab Eyab A.
Published: November 2024

The escalating impacts of climate change on global biodiversity constitute one of the most pressing environmental challenges of our time. This study employs a global survey to gather empirical evidence from a broad spectrum of biologists and ecologists, aiming to confirm the predicted impacts of climate change on biodiversity as theorized in foundational studies. Building upon the seminal work of Parmesan and Yohe (2003) and Root et al. (2003), who documented early evidence of biotic responses to climate change, our research seeks to validate these findings through contemporary observations from professionals actively engaged in the field.

The survey, distributed to over 500 experts worldwide, focused on gathering data on observed shifts in species distributions, alterations in phenological events, and increased frequency of ecosystem disturbances. Our analysis employs advanced statistical techniques to correlate these observations with historical climate data, thereby examining the direct and indirect effects of climatic variations on biological diversity.

Results from this study confirm significant correlations between climate change and various forms of biodiversity disruption, echoing the predictions of Walther et al. (2002) regarding the northward and upward shifts in species distributions. Furthermore, changes in the timing of reproductive events, as detailed by Visser and Both (2005), and increased disturbances such as wildfires and pest outbreaks, support the hypothesis of a climate-driven perturbation in natural systems.

This paper not only substantiates earlier projections but also enhances our understanding of the intricate dynamics between climate change and biodiversity. It emphasizes the urgent need for comprehensive global conservation strategies, as echoed by Hughes et al. (2003), to mitigate these profound impacts. The findings serve as a critical update to the ongoing scientific dialogue, urging for immediate and coordinated policy action.
Biophysical network modeling of temporal and stereotyped sequence propagation of neural activity in the premotor nucleus HVC
Authors: Diab Zeina Bou , Chammas Marc , Daou Arij
Published: November 2024

Stereotyped neural sequences are often exhibited in the brain, yet the neurophysiological mechanisms underlying their generation are not fully understood. Birdsong is a prominent model to study such behavior particularly because juvenile songbirds progressively learn from their tutors and by adulthood are able to sing stereotyped song patterns. The songbird premotor nucleus HVC coordinate motor and auditory activity responsible for learned vocalizations. The HVC comprises three neural populations that has distinctin vitroandin vivoelectrophysiological responses. Typically, models that explain HVC’s network either rely on intrinsic HVC circuitry to propagate sequential activity, rely on extrinsic feedback to advance the sequence or rely on both. Here, we developed a physiologically realistic neural network model incorporating the three classes of HVC neurons based on the ion channels and the synaptic currents that had been pharmacologically identified. Our model is based on a feedforward chain of microcircuits that encode for the different sub-syllabic segments (SSSs) and that interact with each other through structured feedback inhibition. The network reproduced thein vivoactivity patterns of each class of HVC neurons, and unveiled key intrinsic and synaptic mechanisms that govern the sequential propagation of neural activity by highlighting important roles for the T-type Ca2+current, Ca2+-dependent K+current, A-type K+current, hyperpolarization activated inward current, as well as excitatory and inhibitory synaptic currents. The result is a biophysically realistic model that suggests an improved characterization of the HVC network responsible for song production in the songbird.
Gestation length drives brain size and litter size variation in eutherian mammals
Authors: Danis Thodoris , Lin Dana , Caetano Daniel S. , Funston Gregory F. , Rokas Antonis
Published: November 2024

The length of gestation in eutherian mammals, which is key to their reproductive success, is closely connected to other life history traits and with body mass and brain mass, but causal relationships between these variables are unclear. Here, we used an integrative analytical framework to evaluate the evolutionary relationships between gestation length and eight other traits on a dataset of 3,258 eutherian mammals and infer causality. We identify variation in generation length and litter size as the primary predictors of eutherian gestation length variation, whereas additional traits, such as brain mass, significantly predict gestation length only in specific mammalian orders. Using a structural equation modeling approach known as phylogenetic path analysis to infer causality, we find that gestation length variation positively influences brain mass variation and negatively influences litter size variation. Furthermore, body mass causally influences gestation length variation only in certain orders. Consistent with these causal inferences, examination of trait-trait coevolution reinforces that gestation length is strongly positively associated with brain mass, strongly negatively associated with litter size, and only moderately correlated with body mass. These findings reveal how gestation length directly and indirectly influences, and is influenced by, other key eutherian traits. Our study establishes a robust framework for identifying causal relationships within suites of correlated and co-evolving traits.
Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences
Authors: Miedlar Elise , Hamilton Grace E , Witus Samuel R , Gonske Sara J , Riffle Michael , Zelter Alex , Klevit Rachel E , Asbury Charles L , Dimitrova Yoana N , Davis Trisha N
Published: November 2024

Previously, we reconstituted a minimal functional kinetochore from recombinantS. cerevisiaeproteins that was capable of transmitting force from dynamic microtubules to nucleosomes containing the centromere-specific histone variant Cse4 (Hamilton et al. 2020). This work revealed two paths of force transmission through the inner kinetochore: through Mif2 and through the Okp1/Ame1 complex (OA). Here, using a chimeric DNA sequence that contains crucial centromere-determining elements of the budding yeast point centromere, we demonstrate that the presence of centromeric DNA sequences in Cse4-containing nucleosomes significantly strengthens OA-mediated linkages. Our findings indicate that centromeric sequences are important for the transmission of microtubule-based forces to the chromosome.
Lethal Plague Outbreaks in Lake Baikal Hunter–gatherers 5500 Years Ago
Authors: Macleod Ruairidh , Seersholm Frederik , de Sanctis Bianca , Lieverse Angela , Timpson Adrian , Stenderup Jesper T. , Gaunitz Charleen , Vinner Lasse , Schulting Rick , Goriunova Olga Ivanovna , Bazaliiskii Vladimir Ivanovich , Vasiliev Sergei V. , Jessup Erin , Wang Yucheng , Thomas Mark G. , Corbett-Detig Russell , Iversen Astrid K.N. , Weber Andrzej W. , Sikora Martin , Willerslev Eske
Published: November 2024

The rise of zoonotic diseases in prehistory is often associated with the Neolithic agricultural transition1,2. In particular, plague has been linked to population declines in Late Neolithic Europe3,4. Although plague is amongst the most devastating diseases in human history, early strains ofYersinia pestis,the causal agent of plague, lack virulence factors required for the bubonic form5, and their severity remains unclear. Here, we describe the oldest strains of plague reported so far, associated with two early phases of outbreaks among prehistoric hunter–gatherers in the Lake Baikal region in East Siberia, beginning from ∼5600–5400 years ago (cal. BP). These outbreaks occur across four hunter–gatherer cemeteries; the largest of these (Ust’-Ida I) has a 38.7% detection rate for plague infection (39% detection across all sites). By reconstructing kinship pedigrees, we show that small familial groups are affected, consistent with human-to-human spread of the disease, and the first outbreak occurred within a single generation. Intriguingly, the infections appear to have resulted in acute mortality events, especially among children. Zoonotic transmission is separately indicated by aBrucellainfection in one of the children. Interestingly, we see differences in functional genomic variants in the prehistoric plague strains, including in theypmsuperantigen known fromY. pseudotuberculosistoday. The new strains diverge ancestrally to all knownY. pestisdiversity and push back theY. pestisdivergence fromY. pseudotuberculosisby some 2000 years6. Our results show that plague outbreaks happen earlier than previously thought and that these early outbreaks were indeed lethal. The findings challenge the common notion that high population densities and lifestyle changes during the Neolithic transition were prerequisites for plague epidemics.
Computational Design of Metallohydrolases
Authors: Kim Donghyo , Woodbury Seth M. , Ahern Woody , Kalvet Indrek , Hanikel Nikita , Salike Saman , Pellock Samuel J. , Lauko Anna , Hilvert Donald , Baker David
Published: November 2024

New enzymes can be designed by starting from a description of an ideal active site composed of catalytic residues surrounding the reaction transition state(s) and identifying or generating a protein scaffold that supports the site1–7, but there are a few current limitations. First, the catalytic efficiencies achieved by such efforts have generally been quite low, and considerable optimization by directed evolution has been required to reach activities typical of native enzymes.8–10Second, generative AI methods such as RFdiffusion11,12now enable the direct generation of proteins around active sites, but to date, such scaffolding has required specification of both the position in the sequence and the backbone coordinates of the catalytic residue, which complicates sampling. Here we introduce a generative AI method called RFam that overcomes these limitations and use it to design zinc metallohydrolases starting from a density functional theory description of active site geometry. Of 96 designs tested experimentally, the most active has akcat/KMof 23,000 M-1s-1, orders of magnitude higher than previously designed metallohydrolases.6,7,13,14This 148 amino acid protein has a novel fold with an enclosed chamber which positions the reaction substrate nearly perfectly for attack by a catalytic water molecule activated by the bound metal and is predicted by ChemNet15to have a highly preorganized active site. The ability to generate high activity catalysts starting from quantum chemistry calculated active site geometries without experimental optimization should open the door to a new generation of potent designer enzymes.16,17