A Newborn with Genital Ambiguity, 45,X/46,XY Mosaicism, a Jumping Chromosome Y, and Congenital Adrenal Hyperplasia by Lei Zhang, Linda D. Cooley, Sonal R. Chandratre, Atif Ahmed, Jill D. Jacobson

“…Molecular analysis revealed compound heterozygous mutations in the 21-hydroxylase gene (CYP21A2), confirming the diagnosis of CAH. …”
Get full text

Non-small cell lung cancer and the tumor microenvironment: making headway from targeted therapies to advanced immunotherapy by Anna De Lucia, Lucia Mazzotti, Lucia Mazzotti, Anna Gaimari, Anna Gaimari, Matteo Zurlo, Roberta Maltoni, Claudio Cerchione, Sara Bravaccini, Angelo Delmonte, Lucio Crinò, Patricia Borges de Souza, Luigi Pasini, Fabio Nicolini, Fabrizio Bianchi, Manel Juan, Hugo Calderon, Chiara Magnoni, Chiara Magnoni, Luca Gazzola, Luca Gazzola, Paola Ulivi, Massimiliano Mazza

“…Nowadays, targeted therapies remain the gold standard for many patients, but still they suffer from many adverse effects, including unexpected toxicity and intrinsic acquired resistance mutations, which lead to relapse. The adoption of immune checkpoint inhibitors (ICIs) in 2015, has offered exceptional survival benefits for patients without targetable alterations. …”
Get full text

Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax by Caroline A. Coughlin, Dhanvantri Chahar, Marianna Lekakis, Abdessamad A. Youssfi, Lingxiao Li, Evan Roberts, Natalia Campos Gallego, Claude-Henry Volmar, Ola Landgren, Shaun Brothers, Anthony J. Griswold, Catalina Amador, Daniel Bilbao, Francesco Maura, Jonathan H. Schatz

“…Here, we build on recent findings implicating gain-of-function mutations in the BCL10 signaling protein as drivers of resistance to Bruton’s tyrosine kinase (BTK) inhibitors. …”
Get full text

RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties by Barnabas Nyesiga, Mattias Levin, Anna Säll, Anna Rosén, Kim Jansson, Sara Fritzell, Karin Hägerbrand, Dietmar Weilguny, Laura von Schantz

“…The RUBYTM format has a 2 + 2 geometry, where two Fab fragments are linked via their light chains to the C-termini of an IgG, and carries mutations for optimal chain pairing. The unique design enables generation of bsAbs with mAb-like attributes. …”
Get full text

Reduction of monoclonal antibody viscosity using interpretable machine learning by Emily K. Makowski, Hsin-Ting Chen, Tiexin Wang, Lina Wu, Jie Huang, Marissa Mock, Patrick Underhill, Emma Pelegri-O’Day, Erick Maglalang, Dwight Winters, Peter M. Tessier

“…Importantly, we show that the interpretable nature of the model enables the design of mutations that significantly reduce antibody viscosity, which we confirmed experimentally. …”
Get full text

Molecular characterization of feline caliciviruses isolated from several adult cats with atypical infection showing severe flu-like symptoms on a remote island in Ehime, Japan by Yuki Nishisaka, Hikaru Fujii, Fumiko Ono, Sho Kadekaru, Hiroyuki Kogiku, Yumi Une, Shione Takeguchi, Naomi Ohta, Masumi Eto, Chiharu Takeuchi, Seigou Takeuchi, Tetsuko Miki, Akihiko Tokuda, Keiko Ookawa, Yukinobu Tohya, Keita Ishijima, Akiko Okutani, Ken Maeda, Shumpei Watanabe, Shigeru Morikawa

“…The virulent Aoshima strain, which causes atypical FCV infections in cats, may have been derived by acquiring several mutations from a typical strain that chronically infects cats on a remote island.…”
Get full text

Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function by Jennifer L. Schwedler, Maxwell A. Stefan, Christine E. Thatcher, Peter R. McIlroy, Anupama Sinha, Ashlee M. Phillips, Christopher A. Sumner, Colleen M. Courtney, Christina Y. Kim, Dina R. Weilhammer, Brooke Harmon

“…To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab with intact Fc function (hF5-WT) or containing the loss of function Fc mutations L234A and L235A (hF5-LALA) in the context of VEEV infection. …”
Get full text

Interpreting Variants of Uncertain Significance in PCD: Abnormal Splicing Caused by a Missense Variant of DNAAF3 by Haixia Zheng, Chongsheng Cheng, Miao He, Wangji Zhou, Yixuan Li, Jinrong Dai, Ting Zhang, Kai‐Feng Xu, Xue Zhang, Xinlun Tian, Yaping Liu

“…Our findings not only expanded the spectrum of mutations in the DNAAF3 gene but also highlighted the importance of investigating variants of uncertain significance (VUS) for comprehensive genetic diagnoses.…”
Get full text

Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival by Linda Kachuri, Geno A. Guerra, Taishi Nakase, George A. Wendt, Helen M. Hansen, Annette M. Molinaro, Paige Bracci, Lucie McCoy, Terri Rice, John K. Wiencke, Jeanette E. Eckel-Passow, Robert B. Jenkins, Margaret Wrensch, Stephen S. Francis

“…We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. …”
Get full text

Transcriptional and Posttranscriptional Regulations of the HLA-G Gene by Erick C. Castelli, Luciana C. Veiga-Castelli, Layale Yaghi, Philippe Moreau, Eduardo A. Donadi

“…The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. …”
Get full text

Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy by Sarala Raj Murthi, Andreas Petry, Bachuki Shashikadze, Jan B. Stöckl, Manuel Schmid, Gianluca Santamaria, Karin Klingel, Damir Kračun, Xinpei Chen, Sabine Bauer, Joachim P. Schmitt, Florian Flenkenthaler, Josh Gorham, Christopher N. Toepfer, David Potěšil, Pavel Hruška, Zbyněk Zdráhal, Zsuzsanna Mayer, Mathieu Klop, Luisa Lehmann, Yishi Qin, Laura Papanakli, Nadine Spielmann, Alessandra Moretti, Thomas Fröhlich, Peter Ewert, Stefan Holdenrieder, Jonathan G. Seidman, Christine E. Seidman, Agnes Görlach, Cordula M. Wolf

“…Abstract Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. …”
Get full text

Targeting protein kinase C-α prolongs survival and restores liver function in sepsis: Evidence from preclinical models by Ling Xiong, Dustin Beyer, Na Liu, Tina Lehmann, Sophie Neugebauer, Sascha Schaeuble, Oliver Sommerfeld, Philipp Ernst, Carl-Magnus Svensson, Sandor Nietzsche, Sebastian Scholl, Tony Bruns, Nikolaus Gaßler, Markus H. Gräler, Marc Thilo Figge, Gianni Panagiotou, Michael Bauer, Adrian T. Press

“…Midostaurin is the clinically approved active pharmaceutical ingredient in Rydapt, approved for the adjuvant treatment of FTL3-mutated AML. Here, it reduced plasma bile acids and related inflammation in those patients, opening a translational avenue for therapeutics in sepsis. …”
Get full text

Downregulation of MerTK in circulating T cells of patients with non-proliferative diabetic retinopathy by Shimiao Bu, Shimiao Bu, Jiang-Yue Ling, Jiang-Yue Ling, Xiaojun Wu, Xiaojun Wu, Liting Zhang, Liting Zhang, Xiangyu Shi, Lang Huang, Zheng Zhao, Ying Yang, Zongqin Xiang, Yong U. Liu, Yong U. Liu, Yufeng Liu, Yuehong Zhang, Yuehong Zhang

“…Western blot and flow cytometry were also employed to evaluate the protein expression of specific genes.ResultsIn patients with NPDR compared to those with DM alone, MerTK—a gene implicated in inherited retinal dystrophies due to its mutations—was notably downregulated in PBMCs. Through flow cytometry, we assessed the protein levels and cellular distribution of MerTK, finding a predominant expression in monocytes and myeloid-derived suppressor cells (MDSCs), with a marked reduction in CD4+ and CD8+ T cells, as well as in natural killer T (NKT) cells. …”
Get full text

Advanced progress in the genetic modification of the oncolytic HSV-1 virus by Mi Zhou, Mi Zhou, Mi Zhou, Zhenyu Shen, Zhenyu Shen, Zhenyu Shen

“…Importantly, HSV-1 does not integrate into the host genome and cause mutations. The HSV-1 genome can be modified through genetic engineering in two main ways: first, by reducing infectivity and toxicity to normal cells via limited replication and assembly, altered protein-virus receptor binding, and minimized immune evasion; second, by enhancing anticancer activity through disruption of tumor cell metabolism, induction of autophagy, improved immune recognition, and modification of the tumor microenvironment. …”
Get full text

Multi-omic and machine learning analysis of mitochondrial RNA modification genes in lung adenocarcinoma for prognostic and therapeutic implications by Xiao Zhang, Jiatao Liu, Yaolin Cao, Wei Wang, Haoran Lin, Yue Yu

“…Our findings uniquely link MRMS to increased tumor mutational burden, genetic instability, and an immunosuppressive tumor microenvironment characterized by reduced immune cell infiltration and elevated tumor purity. …”
Get full text

Switching to Dolutegravir/lamivudine or Bictegravir/Emtricitabine/Tenofovir alafenamide. A comparative real-world study by Hernando Knobel, Esperanza Cañas-Ruano, Ana Guelar, Pablo Knobel, Judit Villar-García, Alicia González-Mena, Ceclia Canepa, Itziar Arrieta-Aldea, Augustin Marcos, Agustí Abalat-Torrres, Roberto Güerri-Fernández

“…Notably, one patient in D/L group with severe non-adherence and virologic failure developed resistance mutations. Conclusions Switching to either B/T/F or D/L treatment for PLWH was effective and well tolerated in this real-world study. …”
Get full text

Development of new powdery mildew resistant lines in garden pea (Pisum sativum L.) using induced mutagenesis and validation of resistance for the er1 and er2 gene through molecular... by Akhilesh Sharma, Devinder Kumar Banyal, Vinod Janardan Dhole, Bansuli, Ranbir Singh Rana, Rajesh Kumar, Prabhat Kumar, Nimit Kumar, Srishti, Arshia Prashar, Vivek Singh, Anoushka Sharma

“…The efforts were made to develop PM-resistant mutants of popular pea varieties “Lincoln” and “Azad P-1” through induced mutations by following gamma irradiation (300, 400, 500, and 600 Gy) and chemical mutagenesis, i.e., ethyl methane sulfonate (EMS) (0.3% and 0.4%). …”
Get full text

Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML by Helene Sieberer, Michela Luciano, Diana Amend, Constantin Blöchl, Anna Eglseer, Alina Steinkellner, Sebastian Rieser, Ancuela Andosch, Philip Steiner, Laura Hummer, Peter W. Krenn, Hieu-Hoa Dang, Christian G. Huber, Fritz Aberger, Theresa Neuper, Jutta Horejs-Hoeck

“…Abstract FLT3 mutations occur in approximately 25% of all acute myeloid leukemia (AML) patients. …”
Get full text

Influence of human peripheral blood samples preprocessing on the quality of Hi-C libraries by M. M. Gridina, E. Vesna, M. E. Minzhenkova, N. V. Shilova, O. P. Ryzhkova, L. P. Nazarenko, E. O. Belyaeva, I. N. Lebedev, V. S. Fishman

“…Modern high-throughput methods of genome analysis can effectively reveal point mutations and unbalanced chromosomal rearrangements. …”
Get full text

Study on SHP2 Conformational Transition and Structural Characterization of Its High-Potency Allosteric Inhibitors by Molecular Dynamics Simulations Combined with Machine Learning by Baerlike Wujieti, Mingtian Hao, Erxia Liu, Luqi Zhou, Huanchao Wang, Yu Zhang, Wei Cui, Bozhen Chen

“…Aberrant activation and mutations of SHP2 are associated with tumor growth and immune suppression, thus making it a potential target for cancer therapy. …”
Get full text